This document provides a review of lubricants used in pharmaceutical solid dosage forms. It begins with introducing fundamental concepts of lubrication including friction, adhesion, and the four lubrication mechanisms. It then discusses the specific application of lubrication in pharmaceutical manufacturing processes, with a focus on boundary lubrication. Magnesium stearate is examined in detail as the most commonly used lubricant. The document reviews magnesium stearate's effect on compaction dynamics, mechanical properties of compacts, and potential chemical interactions with active pharmaceutical ingredients. It concludes by presenting general principles for selecting lubricants for pharmaceutical formulations.
Detailed description of types of plasticizers, mode of selection, types of effects produced on polymers and optimization of plasticizers in aqueous/organic coating based systems.
This document discusses applications of silicone masterbatch in automotive polypropylene (PP) and thermoplastic polyolefin (TPO) compounds. It summarizes three types of anti-scratch agents used in automotive PP materials: low molecular weight agents, new non-migrating surface agents, and silicone masterbatches. While low molecular weight agents are cheap and effective, they migrate and degrade when exposed to UV light. New non-migrating surface agents do not actually improve scratch resistance and have odor issues. Silicone masterbatches, like Chengdu Silike's LYSI-306 product, are effective at improving scratch resistance without migrating, and are odorless with low VOC emissions. Test data
Jacobian-free Newton Multigrid method for Elastohydrodynamic line contact wit...ijceronline
In this article, a Jacobian-free Newton Multigrid (JFNMG) method is used for the analysis of isothermal, steady state and incompressible Elastohydrodynamic lubrication (EHL) line contact problem. The lubricant is grease and its rheology is described by Hershel-Bulkley constitutive equation. The problem is investigated for smooth contact surfaces. A finite difference scheme, developed after discretizing governing equations on a uniform grid, is used for the solution of the EHL problem. The JFNMG method is applied to the system of algebraic equations, which arise in the scheme, and obtain solution for a wide range of parameters of interest. The proposed scheme not only overcomes the limitations of conventional schemes but is also, stable and fast converging for the investigation of the EHL problems. The JFNMG method approximates Jacobian matrixvector product accurately with much ease without requiring additional storage at each iteration, and avails convergence features of Newton method as well as convergence strategy (up to discretization error) of multigrid. The EHL features, namely, pressure profiles, film shapes and Petrusevich pressure spikes are studied for different parameters of interest. The minimum film thickness decreases for decrease in n, which is a power law index in Hershel-Bulkley model characterizing grease lubricant, with other parameters held constant. There is a noticeable decrease (in height as well as spread) of pressure spike for small values of n, which arrests bearings fatigue life.
Lubricants are added at the final mixing step to minimize their interaction with other ingredients in the formulation. Adding lubricants too early in the mixing process could result in the lubricant coating the surfaces of other ingredients, which could prevent proper blending and homogeneity of the mixture. Keeping the lubricant addition brief also helps minimize this effect.
Scored tablets provide dose flexibility, ease of swallowing and cost savings. However, some problems with scored tablets can be confronted like difficulty of breaking, unequally breaking and loss of mass upon breaking. This paper investigates the effect of score lines on the density distribution using continuum modelling. In keeping with previous work in the pharmaceutical field, a modified Drucker Prager Cap model is described briefly and used in the simulations. Coulomb friction is included between powder and tools. The microcrystalline cellulose (MCC) Vivapur® 102 was used to identify the model parameters using experimental tests with instrumented die, shear cell and diametrical crushing. The obtained results indicate that simulations may be useful not only to determine density distributions within tablets, but also may provide indications about performance of score lines.
Formulation Development and Characterization of Topical Gel for PsoriasisBRNSS Publication Hub
The purpose of this research work was to develop and characterize a tacrolimus (TAC) gel using different
polymers for the treatment of psoriasis. The physicochemical compatibility was confirmed between
TAC and other excipients by Fourier transfer infrared. Formulated gels were characterized for drug
content, viscosity, extrudability, skin irritation study, pH, in vitro diffusion study, and stability. Release
of TAC from all formulations using dialysis membrane into a phosphate buffer pH 6.8 at 37°C was
performed. Optimized batch was selected from this characterization study. Based on the data collected,
it was revealed that TAC has proven to be a promising candidate for delivery through gel in the treatment
of psoriasis.
Influence of manufacturing process on physical and flow characteristic and c...Ghazwa Shawash
REFRANCES:
1. www.pubmed.com :
(1) Garg ,A., Gupta ,M., Bhargava ,H.N.. (2007). Effect of formulation parameters on the release characteristics of propranolol from asymmetric membrane coated tablets. European Journal of Pharmaceutics and Biopharmaceutics. 67(3), 725-731.
(2) Närvänen ,T., Lipsanen ,T., Antikainen ,O., Räikkönen ,H.,Yliruusi ,J.. (2008). Controlling granule size by granulation liquid feed pulsing. International Journal of Pharmaceutics. 357(1-2), 132-138.
(3) Ende ,T.a.m., Moses ,K., Carella ,j., Gadkari ,A., Graul ,W., Otano ,L., Timpano ,J. .( 2007). Improving the Content Uniformity of a Low-Dose Tablet Formulation Through Roller Compaction Optimization. Pharmaceutical Development and Technology. 12(4), 391 – 404.
(4) Alkhatib ,H.S., Aiedeh ,K.M., Bustanji ,Y., Hamed ,S., Mohammad ,M.K., Alkhalidi ,B., Najjar ,S.. (2008). Modulation of buspirone HCl release from hypromellose matrices using chitosan succinate: Implications for pH-independent release. European Journal of Pharmaceutics and Biopharmaceutics.
(5) Brodka-Pfeiffer ,K., Langguth ,P., Grass ,P., Häusler ,H.. (2003). Influence of mechanical activation on the physical stability of salbutamol sulphate. European Journal of Pharmaceutics and Biopharmaceutics. 56(3), 393-400.
(6) El-Sabawi ,D., Price ,R., Edge ,S., Young ,P.M.. (2006). Novel temperature controlled surface dissolution of excipient particles for carrier based dry powder inhaler formulations. 32(2), 243-51.
(7) Bacher ,C., Olsen ,P.M., Bertelsen ,P., Sonnergaard ,J.M.. (2008). Compressibility and compactibility of granules produced by wet and dry granulation. International Journal of Pharmaceutics. 358(1-2), 69-74.
(8) Bock ,T.K., Kraas ,U.. (2001). Experience with the Diosna mini-granulator and assessment of process scalability. European Journal of Pharmaceutics and Biopharmaceutics. 52(3), 297-303.
(9) Badawy ,S.I., Menning ,M.M., Gorko ,M.A., Gilbert ,D.L. (2000). Effect of process parameters on compressibility of granulation manufactured in a high-shear mixer. International Journal of Pharmaceutics. 198(1), 51-61.
2. advanced pharmacetics: physicochemical principle . cherng-ju Kim.publisher,CRC press.ISBN:0849317290.
3. ansels pharmaceutical dosage form and drug delivery system.loyd V.allen Howard C.Ansel Nicholas G.povich.puplisher:Lippincott William &wilkin.8 th edition.ISBN:0781746124.
4. physical pharmacy , Alfred martin ,ph.d. .
Effect of diluent types and soluble diluents particle size on the dissolution...Valentyn Mohylyuk
Effect of different diluents types on the dissolution profile of trimetazidine dihydrochloride and caffeine from Kollidon SR matrix tablets was investigated using microcrystalline cellulose (Avicel PH-101), calcium hydrogen phosphate dihydrate (Emcompress) and sorbitol (Neosorb P100T). The decreasing of mentioned diluents possibility to slow down of model substances dissolution kinetics (at pH 6.8) had follow sequence: Avicel PH-101 > Emcompress > Neosorb P100T.Effect of soluble diluents particle size on dissolution profile of trimetazidine dihydrochloride and caffeine from Kollidon SR matrix tablets was investigated using sorbitol (Neosorb P100T, Neosorb P60 W and Neosorb P30/60) and lactose monohydrate (Sorbolac 400, Granulac 200 and Capsulac 60). The particle size increasing of lactose monohydrate from 11 to 251 μm and sorbitol from 110 to 513 μm decreased dissolution kinetics of model substances from Kollidon SR matrix tablets. Keywords : matrix tablets, Kollidon SR, caffeine, trimetazidine, diluent, particle size.
Detailed description of types of plasticizers, mode of selection, types of effects produced on polymers and optimization of plasticizers in aqueous/organic coating based systems.
This document discusses applications of silicone masterbatch in automotive polypropylene (PP) and thermoplastic polyolefin (TPO) compounds. It summarizes three types of anti-scratch agents used in automotive PP materials: low molecular weight agents, new non-migrating surface agents, and silicone masterbatches. While low molecular weight agents are cheap and effective, they migrate and degrade when exposed to UV light. New non-migrating surface agents do not actually improve scratch resistance and have odor issues. Silicone masterbatches, like Chengdu Silike's LYSI-306 product, are effective at improving scratch resistance without migrating, and are odorless with low VOC emissions. Test data
Jacobian-free Newton Multigrid method for Elastohydrodynamic line contact wit...ijceronline
In this article, a Jacobian-free Newton Multigrid (JFNMG) method is used for the analysis of isothermal, steady state and incompressible Elastohydrodynamic lubrication (EHL) line contact problem. The lubricant is grease and its rheology is described by Hershel-Bulkley constitutive equation. The problem is investigated for smooth contact surfaces. A finite difference scheme, developed after discretizing governing equations on a uniform grid, is used for the solution of the EHL problem. The JFNMG method is applied to the system of algebraic equations, which arise in the scheme, and obtain solution for a wide range of parameters of interest. The proposed scheme not only overcomes the limitations of conventional schemes but is also, stable and fast converging for the investigation of the EHL problems. The JFNMG method approximates Jacobian matrixvector product accurately with much ease without requiring additional storage at each iteration, and avails convergence features of Newton method as well as convergence strategy (up to discretization error) of multigrid. The EHL features, namely, pressure profiles, film shapes and Petrusevich pressure spikes are studied for different parameters of interest. The minimum film thickness decreases for decrease in n, which is a power law index in Hershel-Bulkley model characterizing grease lubricant, with other parameters held constant. There is a noticeable decrease (in height as well as spread) of pressure spike for small values of n, which arrests bearings fatigue life.
Lubricants are added at the final mixing step to minimize their interaction with other ingredients in the formulation. Adding lubricants too early in the mixing process could result in the lubricant coating the surfaces of other ingredients, which could prevent proper blending and homogeneity of the mixture. Keeping the lubricant addition brief also helps minimize this effect.
Scored tablets provide dose flexibility, ease of swallowing and cost savings. However, some problems with scored tablets can be confronted like difficulty of breaking, unequally breaking and loss of mass upon breaking. This paper investigates the effect of score lines on the density distribution using continuum modelling. In keeping with previous work in the pharmaceutical field, a modified Drucker Prager Cap model is described briefly and used in the simulations. Coulomb friction is included between powder and tools. The microcrystalline cellulose (MCC) Vivapur® 102 was used to identify the model parameters using experimental tests with instrumented die, shear cell and diametrical crushing. The obtained results indicate that simulations may be useful not only to determine density distributions within tablets, but also may provide indications about performance of score lines.
Formulation Development and Characterization of Topical Gel for PsoriasisBRNSS Publication Hub
The purpose of this research work was to develop and characterize a tacrolimus (TAC) gel using different
polymers for the treatment of psoriasis. The physicochemical compatibility was confirmed between
TAC and other excipients by Fourier transfer infrared. Formulated gels were characterized for drug
content, viscosity, extrudability, skin irritation study, pH, in vitro diffusion study, and stability. Release
of TAC from all formulations using dialysis membrane into a phosphate buffer pH 6.8 at 37°C was
performed. Optimized batch was selected from this characterization study. Based on the data collected,
it was revealed that TAC has proven to be a promising candidate for delivery through gel in the treatment
of psoriasis.
Influence of manufacturing process on physical and flow characteristic and c...Ghazwa Shawash
REFRANCES:
1. www.pubmed.com :
(1) Garg ,A., Gupta ,M., Bhargava ,H.N.. (2007). Effect of formulation parameters on the release characteristics of propranolol from asymmetric membrane coated tablets. European Journal of Pharmaceutics and Biopharmaceutics. 67(3), 725-731.
(2) Närvänen ,T., Lipsanen ,T., Antikainen ,O., Räikkönen ,H.,Yliruusi ,J.. (2008). Controlling granule size by granulation liquid feed pulsing. International Journal of Pharmaceutics. 357(1-2), 132-138.
(3) Ende ,T.a.m., Moses ,K., Carella ,j., Gadkari ,A., Graul ,W., Otano ,L., Timpano ,J. .( 2007). Improving the Content Uniformity of a Low-Dose Tablet Formulation Through Roller Compaction Optimization. Pharmaceutical Development and Technology. 12(4), 391 – 404.
(4) Alkhatib ,H.S., Aiedeh ,K.M., Bustanji ,Y., Hamed ,S., Mohammad ,M.K., Alkhalidi ,B., Najjar ,S.. (2008). Modulation of buspirone HCl release from hypromellose matrices using chitosan succinate: Implications for pH-independent release. European Journal of Pharmaceutics and Biopharmaceutics.
(5) Brodka-Pfeiffer ,K., Langguth ,P., Grass ,P., Häusler ,H.. (2003). Influence of mechanical activation on the physical stability of salbutamol sulphate. European Journal of Pharmaceutics and Biopharmaceutics. 56(3), 393-400.
(6) El-Sabawi ,D., Price ,R., Edge ,S., Young ,P.M.. (2006). Novel temperature controlled surface dissolution of excipient particles for carrier based dry powder inhaler formulations. 32(2), 243-51.
(7) Bacher ,C., Olsen ,P.M., Bertelsen ,P., Sonnergaard ,J.M.. (2008). Compressibility and compactibility of granules produced by wet and dry granulation. International Journal of Pharmaceutics. 358(1-2), 69-74.
(8) Bock ,T.K., Kraas ,U.. (2001). Experience with the Diosna mini-granulator and assessment of process scalability. European Journal of Pharmaceutics and Biopharmaceutics. 52(3), 297-303.
(9) Badawy ,S.I., Menning ,M.M., Gorko ,M.A., Gilbert ,D.L. (2000). Effect of process parameters on compressibility of granulation manufactured in a high-shear mixer. International Journal of Pharmaceutics. 198(1), 51-61.
2. advanced pharmacetics: physicochemical principle . cherng-ju Kim.publisher,CRC press.ISBN:0849317290.
3. ansels pharmaceutical dosage form and drug delivery system.loyd V.allen Howard C.Ansel Nicholas G.povich.puplisher:Lippincott William &wilkin.8 th edition.ISBN:0781746124.
4. physical pharmacy , Alfred martin ,ph.d. .
Effect of diluent types and soluble diluents particle size on the dissolution...Valentyn Mohylyuk
Effect of different diluents types on the dissolution profile of trimetazidine dihydrochloride and caffeine from Kollidon SR matrix tablets was investigated using microcrystalline cellulose (Avicel PH-101), calcium hydrogen phosphate dihydrate (Emcompress) and sorbitol (Neosorb P100T). The decreasing of mentioned diluents possibility to slow down of model substances dissolution kinetics (at pH 6.8) had follow sequence: Avicel PH-101 > Emcompress > Neosorb P100T.Effect of soluble diluents particle size on dissolution profile of trimetazidine dihydrochloride and caffeine from Kollidon SR matrix tablets was investigated using sorbitol (Neosorb P100T, Neosorb P60 W and Neosorb P30/60) and lactose monohydrate (Sorbolac 400, Granulac 200 and Capsulac 60). The particle size increasing of lactose monohydrate from 11 to 251 μm and sorbitol from 110 to 513 μm decreased dissolution kinetics of model substances from Kollidon SR matrix tablets. Keywords : matrix tablets, Kollidon SR, caffeine, trimetazidine, diluent, particle size.
Study on Preformulation Parameters of Losartan PotassiumSelf
This document summarizes a study on the preformulation parameters of the drug Losartan Potassium. Some key parameters investigated include:
- Losartan Potassium is a white crystalline powder that is freely soluble in water and methanol. It has good to excellent powder flowability.
- The drug showed no incompatibility with common excipients but did show incompatibility with Amlodipine.
- Preformulation studies provide useful information for formulating dosage forms, including the choice of excipients and composition to develop stable and bioavailable drug delivery systems.
formulation and evaluation of microbeadsgurleen kaur
Microencapsulation has been employed to sustain the drug release, reduce or eliminate drug related adverse effects, dose intake and improve the bioavailability inspite drug undergo extensive first pass metabolism ultimately improve the compliance in pharmacotherapy of inflammation and pain.
Microencapsulation by ionotropic gelation technique is one of the widely used method for preparation of calcium alginate beads which has ability to form gels reaction with calcium salts .
Microencapsulation has been employed to sustain the drug release, reduce or eliminate drug related adverse effects, dose intake and improve the bioavailability inspite drug undergo extensive first pass metabolism ultimately improve the compliance in pharmacotherapy of inflammation and pain.
Microencapsulation by ionotropic gelation technique is one of the widely used method for preparation of calcium alginate beads which has ability to form gels reaction with calcium salts .
This document discusses pharmaceutical incompatibilities, which occur when two or more ingredients in a prescription interact in an undesirable way that affects the safety, efficacy, appearance or stability of the medication. It defines three main types of incompatibilities - physical, chemical and therapeutic. Physical incompatibilities involve changes in properties like color, odor or viscosity. Chemical incompatibilities occur due to reactions like oxidation or acid-base interactions. Therapeutic incompatibilities modify a drug's intended pharmacological effects. The document provides examples and explanations of specific incompatibilities within each category.
The document discusses the physics of tablet compression. It describes the processes of compaction, consolidation and compression that tablets undergo in their production. It outlines the main stages of compression including particle rearrangement, deformation, fragmentation and bonding. It also discusses the forces involved and common compaction profiles and equations used to describe the process, including the Heckel and Kawakita equations. The document provides an overview of the key concepts and stages in understanding the physics behind tablet production through compression.
Development and characterization of porous starch curcumin solid dispertion...NikitaGidde
1) The document discusses the preparation and evaluation of solid dispersions of curcumin and porous starch to enhance the solubility of curcumin.
2) Curcumin is poorly water soluble, so various ratios of curcumin-porous starch solid dispersions were prepared by ball milling.
3) The solid dispersions showed improved flow properties and a 1-2 fold increase in curcumin's solubility compared to curcumin alone. They also exhibited significantly faster drug dissolution.
The document describes the development of calcium alginate beads for oral delivery of the antibiotic ceftriaxone sodium. Twelve formulations of calcium alginate beads were developed using an ionotropic gelation method. The optimized formulation achieved high drug entrapment efficiency (>75%) and provided sustained drug release over 10-18 hours. Scanning electron microscopy indicated the coated optimized beads had a smooth surface and fewer pores, slowing the drug release rate compared to uncoated beads. The calcium alginate beads have potential as a drug delivery system for oral administration of ceftriaxone sodium.
This document discusses using gelatin beads as a sustained release drug delivery system. Gelatin beads can provide sustained release of drugs over time by taking advantage of their large surface area and diffusion properties. The document describes preparing and evaluating propranolol HCl loaded gelatin beads using natural polymers gelatin and fish gelatin crosslinked with glutaraldehyde. The beads were evaluated for loading efficiency, yield, in vitro drug release, and stability over 3 months of accelerated conditions. Overall, the document proposes that gelatin beads can serve as a biocompatible drug delivery system for sustained drug release.
Formulation and evaluation ofmetformin HCl micro beads by ionotropic gelation...Sagar Savale
The Metformin HCL Micro Beads is formulated by the Ionotropic Gelation Method. The CMC is a Swellable
polymer is responsible for the Sustained release action or activity. A combination of CMC (Carboxy Methyl
Cellulose) and Sodium Alginate shows better sustained release activity. The PreparedSustained released Micro
Beadsis Evaluated In terms of bulk density, tapped density, angle of repose, Carr’s Index, Swelling Index, Drug
Content, % Encapsulation Efficiency and vitro study. The result associated in Optimized batch is good to
Satisfactory and having a good free flowing property. The Drug Content and % Encapsulation Efficiency values are
within the pharmacopeia limit. The in vitro Dissolution studies shows Maximum percentage of release of drug
(71.15) with in end of 4 Hours.
Plasticizers are chemicals added to polymers to improve flexibility and processing. They work by spacing out polymer molecules, allowing easier movement. Most plasticizers are organic esters added to PVC to make it flexible. Phthalates are the most widely used type, accounting for over 90% of plasticizers. Common phthalate plasticizers include DOP, DEHP, DINP and DIDP. Selection depends on the required properties and application. Health concerns have led to a search for safer alternatives to phthalates.
Effect of friction, distribution of force, compaction and solubility suraj se...Suraj Pund
This document discusses the effects of friction, force distribution, compaction, and solubility in pharmaceutical manufacturing. It describes how interparticulate and die wall friction affect tablet production, and how lubricants can reduce friction. It also explains that compaction involves compressing and consolidating powders through applied force, and describes the different phases of elastic and plastic deformation that occur during compaction. Finally, it defines solubility and discusses its importance for drug bioavailability and therapeutic effectiveness since drugs must be soluble to be absorbed.
Formulation and Evaluation of Risperidone Fast Dissolving TabletsSunil Vadithya
The document discusses the formulation and evaluation of risperidone fast dissolving tablets. Four formulations of risperidone FDTs were developed using different concentrations and combinations of crospovidone and croscarmellose sodium as superdisintegrants. The tablets were prepared by direct compression method and evaluated for characteristics like hardness, friability, thickness, drug content, wetting time, disintegration time and in-vitro drug release. Formulation F2 showed the most promising results with no drug-excipient interactions. Stability studies on F2 for one month also showed acceptable results, making it the optimized risperidone FDT formulation.
Background: The main aim of present research investigation is to formulate the Risperidone Fast Dissolving tablets. Risperidone, an atypical antipsychotic, belongs to BCS Class-II and used for treating schizophrenia, bipolar mania and autism by blocking D2 and 5-HT2A receptors. Methods: The Fast Dissolving tablets of Risperidone were prepared employing different concentrations of Crospovidone and Croscarmellose sodium in different combinations as a Superdisintegrants by Direct Compression technique using 32 factorial design. The concentration of Crospovidone and Croscarmellose sodium was selected as independent variables, X1 and X2 respectively whereas, wetting time, Disintegration time, t50% ,t90%were selected as dependent variables. Results and Discussion:
Totally nine formulations were designed, preapred and are evaluated for hardness, friability, thickness, Assay, Wetting time, Disintegration time, In-vitro drug release. From the Results concluded that all the formulation were found to be with in the Pharmacopoeial limits and the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for Wetting time, Disintegration time, t50%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations (C1, C2). According to SUPAC guidelines the formulation (F5) containing combination of 10% Crospovidone and 10% Croscarmellose, is the most similar formulation (similarity factor f2= 93.556, dissimilarity factor f1= 0.976& No significant difference, t= 0.022) to marketed product (RISPERDAL-4). Conclusion: The selected formulation (F5) follows First order, Higuchi’s kinetics, mechanism of drug release was found to be Fickian Diffusion (n= 0.383).
Formulation and evaluation of rapimelts of EletriptanSriramNagarajan18
This document describes the formulation and evaluation of rapid-melting tablets containing the drug Eletriptan. Twelve formulations were created using different superdisintegrants like crospovidone, cros carmellose sodium, and sodium starch glycolate. The tablets were prepared by direct compression method and evaluated for properties like hardness, thickness, friability, drug content and in-vitro drug release. Formulation F3 with 10% crospovidone showed maximum drug release of 99.9% within 6 minutes and was selected as the optimized formulation based on rapid disintegration time of 16.33 seconds and high drug release. Fourier transform infrared spectroscopy confirmed no drug-excipient interactions in the optimized formulation.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
Solubility and dissolution enhancement of BCS class ii drug Piroxicam by soli...Makrani Shaharukh
The Present study was conducted to improve solubility and dissolution of poor water soluble drug Piroxicam. In this research work, Piroxicam Solid Dispersion was prepared kneading method by using, Guar Gum as a carrier. Drug and carriers weight ratio were1:1 to 1:5. The properties of solid were evaluated using Fourier Transform Infra red (FTIR) Spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and solubility and dissolution studies. The FTIR Spectroscopy showed no chemical interaction between Piroxicam and carrier. DSC studies indicated their no change of melting point of Piroxicam in Solid Dispersion. SEM result showed that Piroxicam was dispersed and was present as amorphous state in the solid dispersions. Solubility of Solid dispersions was highest at Ratio 1:5 is 0.319±0.02 mg/mL. The drug release data of solid dispersion revealed that formulation F5 exhibited more than 95 % drug release after 60 min. Finally we conclude that the solubility & dissolution enhancement is depend on nature and amount of the carrier and when increases the carrier increase the solubility of Piroxicam. Solid dispersion system of Piroxicam and carriers used could improve the solubility and dissolution rate of Piroxicam.
The document discusses research into producing particle boards from para rubber wood flour, coconut flour, and recycled plastic. It examines the effects of adding different ratios of para wood flour on the mechanical properties of plastic composites. Tests were conducted to determine the tensile strength, flexural strength, impact strength, and melt flow index of samples. Overall, tensile strength decreased while tensile modulus increased with higher wood flour content. Flexural strength also decreased as wood flour was added. Coconut flour was then added and resulted in increased tensile strength but decreased tensile modulus and flexural modulus. The melt flow index decreased with both wood and coconut flour fillers.
Testing of Already Existing and Developing New Compaction Equations during C...IJMER
Powder Metallurgy (P/M) processing of materials to produce conventional P/M parts
involve the compaction of the pre-determined mass of individual elemental, mixed elemental metal
powders or alloy powders and or composite powders into green compacts and sintering them under
reducing atmosphere and or under other protective coatings, thus, after sintering producing
products after mild machining operations. Therefore, compaction represents one of the most
important stages in the production of engineering components using the P/M route. However, the
physical properties such as density and the stress distribution in the green compacts are determined
not only by the properties of the constituents of the powder or the powder blend, but, also by the
pressing modes and schedules. Thus, the present investigation pertains to generate experimental
data on the compaction behaviour of Fe-1.05% graphitesystems with two different iron particle size
ranges and two different powder masses in order to highlight the various aspects of compaction and
also testing out the already existing compaction equations and search for the new ones. Powder
blends of two different iron powder particle size ranges, namely, -106+53µm and -150+106µm
respectively were blended with the required amount of graphite powder of 3 – 5 µm sizes for a
period of 32 hours. Compaction studies have been carried out for two different amounts of both
powder blends. The two amounts taken were 65g and 85g respectively. However, the main attempt
was made to record the load and the corresponding heights and the top punch displacements for
every two tons (0.02MN) of load which was applied in the steps of 0.02MN. Various equations for
compaction were attempted empirically and the already existing ones were also tested. Critical
analysis of the experimental data and the calculated parameters have resulted into several
compaction equations which were arrived at empirically. The regression coefficient ‘R2
’ in each
case where compactions equations were empirically obtained was in very much close proximity to
unity. However, it has been also confirmed that the data of the present investigation were well
taken up by the earlier compactions equations, thus, validating them comprehensively.
Compaction and compression of powder
Physics of tablet compression, mechanism of tablet, bonding of tablets, the effect of compress
ional force on tablet properties, effect of lubricants on tablet compression and binding,
instrumented tablet machines and tooling, problems associated with large scale manufacturing
of tablets.
Technical Approaches to Improving the Scratch Resistance of TPO. Part I: Su...Jim Botkin
A review of the effects of additive systems based on surface lubricants in enhancing the scratch resistance of TPO, with an emphasis on automotive applications. Presented at the SPE Automotive TPO Global Conference, October 2007.
Tribology is the science of interacting surfaces in relative motion, including friction, lubrication, and wear. Proper lubrication is essential for diesel engines, which require lubricants that can satisfy a variety of conditions from hydrodynamic fluid film lubrication to boundary lubrication. New technologies like pulse lubrication systems electronically control cylinder oil injection to optimize lubrication based on engine load. Both over-lubrication and under-lubrication can cause damage, so maintaining the proper oil dosage is important for engine performance and component life.
The document discusses key steps in the manufacturing process of solid dosage forms including granulation, drying, blending, tableting, and coating if applicable. It identifies critical process parameters that can significantly affect drug release such as drug particle size, excipient quality, granulation equipment, process variables like binder amount and time, and manufacturing steps. The document also provides examples of process variables and responses measured for solid dosage forms and diagrams of tablet manufacturing equipment.
Study on Preformulation Parameters of Losartan PotassiumSelf
This document summarizes a study on the preformulation parameters of the drug Losartan Potassium. Some key parameters investigated include:
- Losartan Potassium is a white crystalline powder that is freely soluble in water and methanol. It has good to excellent powder flowability.
- The drug showed no incompatibility with common excipients but did show incompatibility with Amlodipine.
- Preformulation studies provide useful information for formulating dosage forms, including the choice of excipients and composition to develop stable and bioavailable drug delivery systems.
formulation and evaluation of microbeadsgurleen kaur
Microencapsulation has been employed to sustain the drug release, reduce or eliminate drug related adverse effects, dose intake and improve the bioavailability inspite drug undergo extensive first pass metabolism ultimately improve the compliance in pharmacotherapy of inflammation and pain.
Microencapsulation by ionotropic gelation technique is one of the widely used method for preparation of calcium alginate beads which has ability to form gels reaction with calcium salts .
Microencapsulation has been employed to sustain the drug release, reduce or eliminate drug related adverse effects, dose intake and improve the bioavailability inspite drug undergo extensive first pass metabolism ultimately improve the compliance in pharmacotherapy of inflammation and pain.
Microencapsulation by ionotropic gelation technique is one of the widely used method for preparation of calcium alginate beads which has ability to form gels reaction with calcium salts .
This document discusses pharmaceutical incompatibilities, which occur when two or more ingredients in a prescription interact in an undesirable way that affects the safety, efficacy, appearance or stability of the medication. It defines three main types of incompatibilities - physical, chemical and therapeutic. Physical incompatibilities involve changes in properties like color, odor or viscosity. Chemical incompatibilities occur due to reactions like oxidation or acid-base interactions. Therapeutic incompatibilities modify a drug's intended pharmacological effects. The document provides examples and explanations of specific incompatibilities within each category.
The document discusses the physics of tablet compression. It describes the processes of compaction, consolidation and compression that tablets undergo in their production. It outlines the main stages of compression including particle rearrangement, deformation, fragmentation and bonding. It also discusses the forces involved and common compaction profiles and equations used to describe the process, including the Heckel and Kawakita equations. The document provides an overview of the key concepts and stages in understanding the physics behind tablet production through compression.
Development and characterization of porous starch curcumin solid dispertion...NikitaGidde
1) The document discusses the preparation and evaluation of solid dispersions of curcumin and porous starch to enhance the solubility of curcumin.
2) Curcumin is poorly water soluble, so various ratios of curcumin-porous starch solid dispersions were prepared by ball milling.
3) The solid dispersions showed improved flow properties and a 1-2 fold increase in curcumin's solubility compared to curcumin alone. They also exhibited significantly faster drug dissolution.
The document describes the development of calcium alginate beads for oral delivery of the antibiotic ceftriaxone sodium. Twelve formulations of calcium alginate beads were developed using an ionotropic gelation method. The optimized formulation achieved high drug entrapment efficiency (>75%) and provided sustained drug release over 10-18 hours. Scanning electron microscopy indicated the coated optimized beads had a smooth surface and fewer pores, slowing the drug release rate compared to uncoated beads. The calcium alginate beads have potential as a drug delivery system for oral administration of ceftriaxone sodium.
This document discusses using gelatin beads as a sustained release drug delivery system. Gelatin beads can provide sustained release of drugs over time by taking advantage of their large surface area and diffusion properties. The document describes preparing and evaluating propranolol HCl loaded gelatin beads using natural polymers gelatin and fish gelatin crosslinked with glutaraldehyde. The beads were evaluated for loading efficiency, yield, in vitro drug release, and stability over 3 months of accelerated conditions. Overall, the document proposes that gelatin beads can serve as a biocompatible drug delivery system for sustained drug release.
Formulation and evaluation ofmetformin HCl micro beads by ionotropic gelation...Sagar Savale
The Metformin HCL Micro Beads is formulated by the Ionotropic Gelation Method. The CMC is a Swellable
polymer is responsible for the Sustained release action or activity. A combination of CMC (Carboxy Methyl
Cellulose) and Sodium Alginate shows better sustained release activity. The PreparedSustained released Micro
Beadsis Evaluated In terms of bulk density, tapped density, angle of repose, Carr’s Index, Swelling Index, Drug
Content, % Encapsulation Efficiency and vitro study. The result associated in Optimized batch is good to
Satisfactory and having a good free flowing property. The Drug Content and % Encapsulation Efficiency values are
within the pharmacopeia limit. The in vitro Dissolution studies shows Maximum percentage of release of drug
(71.15) with in end of 4 Hours.
Plasticizers are chemicals added to polymers to improve flexibility and processing. They work by spacing out polymer molecules, allowing easier movement. Most plasticizers are organic esters added to PVC to make it flexible. Phthalates are the most widely used type, accounting for over 90% of plasticizers. Common phthalate plasticizers include DOP, DEHP, DINP and DIDP. Selection depends on the required properties and application. Health concerns have led to a search for safer alternatives to phthalates.
Effect of friction, distribution of force, compaction and solubility suraj se...Suraj Pund
This document discusses the effects of friction, force distribution, compaction, and solubility in pharmaceutical manufacturing. It describes how interparticulate and die wall friction affect tablet production, and how lubricants can reduce friction. It also explains that compaction involves compressing and consolidating powders through applied force, and describes the different phases of elastic and plastic deformation that occur during compaction. Finally, it defines solubility and discusses its importance for drug bioavailability and therapeutic effectiveness since drugs must be soluble to be absorbed.
Formulation and Evaluation of Risperidone Fast Dissolving TabletsSunil Vadithya
The document discusses the formulation and evaluation of risperidone fast dissolving tablets. Four formulations of risperidone FDTs were developed using different concentrations and combinations of crospovidone and croscarmellose sodium as superdisintegrants. The tablets were prepared by direct compression method and evaluated for characteristics like hardness, friability, thickness, drug content, wetting time, disintegration time and in-vitro drug release. Formulation F2 showed the most promising results with no drug-excipient interactions. Stability studies on F2 for one month also showed acceptable results, making it the optimized risperidone FDT formulation.
Background: The main aim of present research investigation is to formulate the Risperidone Fast Dissolving tablets. Risperidone, an atypical antipsychotic, belongs to BCS Class-II and used for treating schizophrenia, bipolar mania and autism by blocking D2 and 5-HT2A receptors. Methods: The Fast Dissolving tablets of Risperidone were prepared employing different concentrations of Crospovidone and Croscarmellose sodium in different combinations as a Superdisintegrants by Direct Compression technique using 32 factorial design. The concentration of Crospovidone and Croscarmellose sodium was selected as independent variables, X1 and X2 respectively whereas, wetting time, Disintegration time, t50% ,t90%were selected as dependent variables. Results and Discussion:
Totally nine formulations were designed, preapred and are evaluated for hardness, friability, thickness, Assay, Wetting time, Disintegration time, In-vitro drug release. From the Results concluded that all the formulation were found to be with in the Pharmacopoeial limits and the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for Wetting time, Disintegration time, t50%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations (C1, C2). According to SUPAC guidelines the formulation (F5) containing combination of 10% Crospovidone and 10% Croscarmellose, is the most similar formulation (similarity factor f2= 93.556, dissimilarity factor f1= 0.976& No significant difference, t= 0.022) to marketed product (RISPERDAL-4). Conclusion: The selected formulation (F5) follows First order, Higuchi’s kinetics, mechanism of drug release was found to be Fickian Diffusion (n= 0.383).
Formulation and evaluation of rapimelts of EletriptanSriramNagarajan18
This document describes the formulation and evaluation of rapid-melting tablets containing the drug Eletriptan. Twelve formulations were created using different superdisintegrants like crospovidone, cros carmellose sodium, and sodium starch glycolate. The tablets were prepared by direct compression method and evaluated for properties like hardness, thickness, friability, drug content and in-vitro drug release. Formulation F3 with 10% crospovidone showed maximum drug release of 99.9% within 6 minutes and was selected as the optimized formulation based on rapid disintegration time of 16.33 seconds and high drug release. Fourier transform infrared spectroscopy confirmed no drug-excipient interactions in the optimized formulation.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
Solubility and dissolution enhancement of BCS class ii drug Piroxicam by soli...Makrani Shaharukh
The Present study was conducted to improve solubility and dissolution of poor water soluble drug Piroxicam. In this research work, Piroxicam Solid Dispersion was prepared kneading method by using, Guar Gum as a carrier. Drug and carriers weight ratio were1:1 to 1:5. The properties of solid were evaluated using Fourier Transform Infra red (FTIR) Spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and solubility and dissolution studies. The FTIR Spectroscopy showed no chemical interaction between Piroxicam and carrier. DSC studies indicated their no change of melting point of Piroxicam in Solid Dispersion. SEM result showed that Piroxicam was dispersed and was present as amorphous state in the solid dispersions. Solubility of Solid dispersions was highest at Ratio 1:5 is 0.319±0.02 mg/mL. The drug release data of solid dispersion revealed that formulation F5 exhibited more than 95 % drug release after 60 min. Finally we conclude that the solubility & dissolution enhancement is depend on nature and amount of the carrier and when increases the carrier increase the solubility of Piroxicam. Solid dispersion system of Piroxicam and carriers used could improve the solubility and dissolution rate of Piroxicam.
The document discusses research into producing particle boards from para rubber wood flour, coconut flour, and recycled plastic. It examines the effects of adding different ratios of para wood flour on the mechanical properties of plastic composites. Tests were conducted to determine the tensile strength, flexural strength, impact strength, and melt flow index of samples. Overall, tensile strength decreased while tensile modulus increased with higher wood flour content. Flexural strength also decreased as wood flour was added. Coconut flour was then added and resulted in increased tensile strength but decreased tensile modulus and flexural modulus. The melt flow index decreased with both wood and coconut flour fillers.
Testing of Already Existing and Developing New Compaction Equations during C...IJMER
Powder Metallurgy (P/M) processing of materials to produce conventional P/M parts
involve the compaction of the pre-determined mass of individual elemental, mixed elemental metal
powders or alloy powders and or composite powders into green compacts and sintering them under
reducing atmosphere and or under other protective coatings, thus, after sintering producing
products after mild machining operations. Therefore, compaction represents one of the most
important stages in the production of engineering components using the P/M route. However, the
physical properties such as density and the stress distribution in the green compacts are determined
not only by the properties of the constituents of the powder or the powder blend, but, also by the
pressing modes and schedules. Thus, the present investigation pertains to generate experimental
data on the compaction behaviour of Fe-1.05% graphitesystems with two different iron particle size
ranges and two different powder masses in order to highlight the various aspects of compaction and
also testing out the already existing compaction equations and search for the new ones. Powder
blends of two different iron powder particle size ranges, namely, -106+53µm and -150+106µm
respectively were blended with the required amount of graphite powder of 3 – 5 µm sizes for a
period of 32 hours. Compaction studies have been carried out for two different amounts of both
powder blends. The two amounts taken were 65g and 85g respectively. However, the main attempt
was made to record the load and the corresponding heights and the top punch displacements for
every two tons (0.02MN) of load which was applied in the steps of 0.02MN. Various equations for
compaction were attempted empirically and the already existing ones were also tested. Critical
analysis of the experimental data and the calculated parameters have resulted into several
compaction equations which were arrived at empirically. The regression coefficient ‘R2
’ in each
case where compactions equations were empirically obtained was in very much close proximity to
unity. However, it has been also confirmed that the data of the present investigation were well
taken up by the earlier compactions equations, thus, validating them comprehensively.
Compaction and compression of powder
Physics of tablet compression, mechanism of tablet, bonding of tablets, the effect of compress
ional force on tablet properties, effect of lubricants on tablet compression and binding,
instrumented tablet machines and tooling, problems associated with large scale manufacturing
of tablets.
Technical Approaches to Improving the Scratch Resistance of TPO. Part I: Su...Jim Botkin
A review of the effects of additive systems based on surface lubricants in enhancing the scratch resistance of TPO, with an emphasis on automotive applications. Presented at the SPE Automotive TPO Global Conference, October 2007.
Tribology is the science of interacting surfaces in relative motion, including friction, lubrication, and wear. Proper lubrication is essential for diesel engines, which require lubricants that can satisfy a variety of conditions from hydrodynamic fluid film lubrication to boundary lubrication. New technologies like pulse lubrication systems electronically control cylinder oil injection to optimize lubrication based on engine load. Both over-lubrication and under-lubrication can cause damage, so maintaining the proper oil dosage is important for engine performance and component life.
The document discusses key steps in the manufacturing process of solid dosage forms including granulation, drying, blending, tableting, and coating if applicable. It identifies critical process parameters that can significantly affect drug release such as drug particle size, excipient quality, granulation equipment, process variables like binder amount and time, and manufacturing steps. The document also provides examples of process variables and responses measured for solid dosage forms and diagrams of tablet manufacturing equipment.
Evaluation of the physical & mechanical properties of high drug load formulations (Metformin, APAP, and Aspirin) - Wet Granulation vs. Foam technique
Experimental Investigation of Tribological Properties using Nanoparticles as ...IRJET Journal
This document describes an experimental investigation of the tribological properties of engine oil modified with nanoparticles. Molybdenum disulfide (MoS2) and copper oxide (CuO) nanoparticles were added to SAE 20W50 engine oil at concentrations of 0.25%, 0.5%, and 1% by weight. Tests were conducted to evaluate the friction, wear, and viscosity properties of the modified oils. The results showed that adding MoS2 or CuO nanoparticles improved the oil's friction reduction and anti-wear performance compared to the unmodified oil. Specifically, the modified oils exhibited lower coefficients of friction and wear rates. This tribological behavior is attributed to the nanoparticles depositing on rubbing surfaces during testing.
The tribological properties of textured surfaces of brass and aluminum were compared with untextured surfaces of the same specimens. This was done to research the effect of micro-dimples and their geometry parameters in reducing the wear of samples tested under lubricated contact with a ball-on-flat reciprocating tribometer.
Development of a processed composite restorationIoannis Skliris
This document summarizes the principles and clinical procedures for bonding laboratory-processed composite restorations. It discusses the importance of optimizing the adhesion between the restoration and tooth structure through proper surface preparation and moisture control. A key factor in the long-term success of these restorations is creating a strong, durable bond between the tooth, resin cement, and restoration material. The document outlines the clinical steps for etching and applying adhesive to both the tooth and restoration to achieve this bond. It also addresses factors like restoration fit and finishing/polishing that influence marginal integrity and wear resistance.
TRIBIOLOGY IS A TOOL FOR SENSORY EVALUATION OF DAIRY FOODSIRJET Journal
Tribology is a tool used to evaluate the sensory properties of dairy foods through simulating the oral processing of food. It works by measuring the friction coefficient between two surfaces, similar to how food interacts with the tongue and palate in the mouth. Various types of tribometers exist that can measure properties like smoothness, creaminess, and slipperiness. The tribometer operates on tribology principles like the Stribeck curve to evaluate a food's lubrication behavior under different loading and speed conditions. Tribology has numerous applications in evaluating dairy foods and detecting adulteration, and provides a method to study how components like fat, protein, starch influence sensory attributes of foods like milk, yogurt and curd.
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
This document discusses damage equivalent test methodologies for evaluating journal bearing systems. It describes two damage equivalent laboratory test methods that can visualize performance parameters like friction, wear, and seizure events. The results from these test methods provide accurate insights into how parameters like material coatings, lubricant additives, and viscosity changes affect the performance and robustness of bearing systems. The test methods allow for efficient investigation and optimization of bearing materials, coatings, lubricants, and system design within shortened product development timelines.
This document discusses the tribological (lubrication) properties of four vegetable oils: groundnut oil, red palm oil, palm kernel oil, and refined cottonseed oil. It aims to experimentally determine the density, viscosity, flash point, pour point, specific gravity, and heat capacity of the oils. The influence of temperature on density and viscosity will be investigated, and mathematical models will be developed to relate density and specific gravity to temperature. Viscosity indices will also be determined for each oil. The research seeks to provide data on the tribological properties of the oils that can inform the design of vegetable oil-based lubricants.
This document summarizes the emerging role of nanosuspensions in drug delivery systems. It discusses how nanosuspensions can increase the bioavailability of poorly soluble drugs by increasing their surface area and dissolution rate. Various preparation methods are described, including precipitation, homogenization, and wet milling. The document also covers the principles behind how nanosizing increases solubility and dissolution according to classical equations. The advantages of nanosuspensions for drug delivery via various routes are discussed.
Tribology is the study of friction, lubrication, and wear between interacting surfaces in relative motion. It helps improve machine reliability and reduce failures. Reynolds' equation, derived in 1886, quantifies fluid film lubrication and allows prediction of hydrodynamic, hydrostatic, and squeeze film mechanisms by modeling pressure as a function of coordinates and time. The equation assumes laminar flow of an incompressible Newtonian fluid with negligible inertia and pressure gradients in the film thickness direction.
Direct Compression is the simplest form of oral dosage production as it contains the fewest process stages, leading to a shorter process cycle and faster production times.
An approach to reduction of frictional losses in heavy duty diesel engine by ...NAGESH Dewangan
This document presents an approach to reducing frictional losses in heavy duty diesel engines through surface texturing to reduce hydrodynamic friction. The study textures cylinder liner samples with different depth elliptical textures and tests them on a tribometer. Results show the textured surfaces have less wear and increased oil film thickness compared to untreated surfaces, leading to lower friction in the hydrodynamic lubrication regime. The conclusions are that the novel surface texturing decreases hydrodynamic friction and only the texture depth differs between the tested samples.
1) Surface tension arises from cohesive forces between liquid molecules, creating a "skin" at the liquid's surface. It plays an important role in food processing operations by influencing emulsion formation, foaming, and coating uniformity.
2) Several techniques can be used to measure surface tension, including the pendant drop method, Wilhelmy plate method, and maximum bubble pressure method.
3) Challenges in food processing due to surface tension effects include uneven coating, unstable emulsions, inconsistent foaming, and droplet coalescence. Solutions include controlling application methods, choosing appropriate emulsifiers and stabilizers, optimizing formulations, and conducting quality testing.
Direct compression is the most advanced technology. It involves only blending and compression. Thus offering advantage particularly in terms of speedy production. Because it requires fewer unit operations, less machinery, reduced number of personnel and considerably less processing time along with increased product stability.
The document presents an experimental study on the effect of various parameters on the tribological performance of a nano lubricant containing multi-walled carbon nanotubes (MWCNT). Design of experiments was used to study the effect of four factors - MWCNT quantity, surfactant quantity, load, and speed. Experiments were conducted using a block-on-disk tribometer with four levels of each factor. The results showed that speed and MWCNT quantity had the greatest effect on wear, followed by surfactant quantity and load. The interaction between load and surfactant quantity and between load and MWCNT quantity were also significant. The minimum wear was achieved with 0.05% MWCNT in the nano lubric
This document presents an experimental study on the parameters affecting the tribological performance of nano lubricant containing multi-walled carbon nanotubes (MWCNT) using design of experiments (DOE). Four factors were studied - MWCNT quantity, surfactant quantity, load, and speed. Experiments were conducted using a block and disk test setup to measure wear. The results showed that speed and MWCNT quantity had the greatest effect on wear, followed by surfactant quantity and load. The interaction between load and surfactant quantity and between load and MWCNT quantity were also significant. The study concluded that adding 0.05% MWCNT to the nano lubricant significantly reduced wear under different load and speed conditions
The document discusses lubricants and glidants used in pharmaceutical formulations. It defines lubricants as substances that reduce friction during tablet ejection from the die to prevent adhesion. Common lubricants include magnesium stearate and talc. Glidants improve powder flowability by reducing interparticulate friction. While lubricants prevent tablet sticking and smooth ejection, glidants specifically enhance flow. The document provides details on lubricant classification, mechanisms of action, monographs for magnesium stearate and talc, and differences between lubricants and glidants.
Infomatica, as it stands today, is a manifestation of our values, toil, and dedication towards imparting knowledge to the pupils of the society. Visit us/l http://www.infomaticaacademy.com/
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
The binding of cosmological structures by massless topological defectsSérgio Sacani
Assuming spherical symmetry and weak field, it is shown that if one solves the Poisson equation or the Einstein field
equations sourced by a topological defect, i.e. a singularity of a very specific form, the result is a localized gravitational
field capable of driving flat rotation (i.e. Keplerian circular orbits at a constant speed for all radii) of test masses on a thin
spherical shell without any underlying mass. Moreover, a large-scale structure which exploits this solution by assembling
concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
light in the same manner as an equipotential (isothermal) sphere. Thus, the need for dark matter or modified gravity theory is
mitigated, at least in part.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
The use of Nauplii and metanauplii artemia in aquaculture (brine shrimp).pptxMAGOTI ERNEST
Although Artemia has been known to man for centuries, its use as a food for the culture of larval organisms apparently began only in the 1930s, when several investigators found that it made an excellent food for newly hatched fish larvae (Litvinenko et al., 2023). As aquaculture developed in the 1960s and ‘70s, the use of Artemia also became more widespread, due both to its convenience and to its nutritional value for larval organisms (Arenas-Pardo et al., 2024). The fact that Artemia dormant cysts can be stored for long periods in cans, and then used as an off-the-shelf food requiring only 24 h of incubation makes them the most convenient, least labor-intensive, live food available for aquaculture (Sorgeloos & Roubach, 2021). The nutritional value of Artemia, especially for marine organisms, is not constant, but varies both geographically and temporally. During the last decade, however, both the causes of Artemia nutritional variability and methods to improve poorquality Artemia have been identified (Loufi et al., 2024).
Brine shrimp (Artemia spp.) are used in marine aquaculture worldwide. Annually, more than 2,000 metric tons of dry cysts are used for cultivation of fish, crustacean, and shellfish larva. Brine shrimp are important to aquaculture because newly hatched brine shrimp nauplii (larvae) provide a food source for many fish fry (Mozanzadeh et al., 2021). Culture and harvesting of brine shrimp eggs represents another aspect of the aquaculture industry. Nauplii and metanauplii of Artemia, commonly known as brine shrimp, play a crucial role in aquaculture due to their nutritional value and suitability as live feed for many aquatic species, particularly in larval stages (Sorgeloos & Roubach, 2021).
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
Unlocking the mysteries of reproduction: Exploring fecundity and gonadosomati...AbdullaAlAsif1
The pygmy halfbeak Dermogenys colletei, is known for its viviparous nature, this presents an intriguing case of relatively low fecundity, raising questions about potential compensatory reproductive strategies employed by this species. Our study delves into the examination of fecundity and the Gonadosomatic Index (GSI) in the Pygmy Halfbeak, D. colletei (Meisner, 2001), an intriguing viviparous fish indigenous to Sarawak, Borneo. We hypothesize that the Pygmy halfbeak, D. colletei, may exhibit unique reproductive adaptations to offset its low fecundity, thus enhancing its survival and fitness. To address this, we conducted a comprehensive study utilizing 28 mature female specimens of D. colletei, carefully measuring fecundity and GSI to shed light on the reproductive adaptations of this species. Our findings reveal that D. colletei indeed exhibits low fecundity, with a mean of 16.76 ± 2.01, and a mean GSI of 12.83 ± 1.27, providing crucial insights into the reproductive mechanisms at play in this species. These results underscore the existence of unique reproductive strategies in D. colletei, enabling its adaptation and persistence in Borneo's diverse aquatic ecosystems, and call for further ecological research to elucidate these mechanisms. This study lends to a better understanding of viviparous fish in Borneo and contributes to the broader field of aquatic ecology, enhancing our knowledge of species adaptations to unique ecological challenges.
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
1. Lubricants 2014, 2, 21-43; doi:10.3390/lubricants2010021
lubricants
ISSN 2075-4442
www.mdpi.com/journal/lubricants
Review
Lubricants in Pharmaceutical Solid Dosage Forms
Jinjiang Li * and Yongmei Wu
Drug Product Science & Technology, Bristol-Myers Squibb Corporation,
1 Squibb Dr., New Brunswick, NJ 08903, USA; E-Mail: yongmei.wu@bms.com
* Author to whom correspondence should be addressed; E-Mail: jinjiang.li@bms.com;
Tel.: +1-732-227-6584; Fax: +1-732-227-3784.
Received: 18 December 2013; in revised form: 21 January 2014 / Accepted: 24 January 2014 /
Published: 25 February 2014
Abstract: Lubrication plays a key role in successful manufacturing of pharmaceutical solid
dosage forms; lubricants are essential ingredients in robust formulations to achieve this.
Although many failures in pharmaceutical manufacturing operations are caused by issues
related to lubrication, in general, lubricants do not gain adequate attention in the
development of pharmaceutical formulations. In this paper, the fundamental background on
lubrication is introduced, in which the relationships between lubrication and friction/adhesion
forces are discussed. Then, the application of lubrication in the development of pharmaceutical
products and manufacturing processes is discussed with an emphasis on magnesium stearate.
In particular, the effect of its hydration state (anhydrate, monohydrate, dihydrate, and
trihydrate) and its powder characteristics on lubrication efficiency, as well as product and
process performance is summarized. In addition, the impact of lubrication on the dynamics
of compaction/compression processes and on the mechanical properties of compacts/tablets
is presented. Furthermore, the online monitoring of magnesium stearate in a blending
process is briefly mentioned. Finally, the chemical compatibility of active pharmaceutical
ingredient (API) with magnesium stearate and its reactive impurities is reviewed with
examples from the literature illustrating the various reaction mechanisms involved.
Keywords: lubricants; boundary lubrication; magnesium stearate; friction; adhesion; the
maximum compression pressure; ribbon and tablet density; chemical incompatibility
OPEN ACCESS
2. Lubricants 2014, 2 22
1. Introduction
A lubricant, an additive to reduce friction, is an essential component of a drug formula since
lubrication is often required to ensure the success of pharmaceutical manufacturing. Historically, use of
animal fats as lubricants to reduce friction in transportation can be traced back to Egyptian time.
However, the development of modern tribology, which is the study of friction and lubrication, did not
gain ground until Frank P. Bowden established a research laboratory on friction, lubrication, and
bearings in Melbourne, Australia during World War II [1]. Since then, a systematic study on friction and
lubrication, termed “tribology”, was initiated. Lately, due to the development of instrumentations in
surface and interfacial characterization, and force measurements as well as the improved understanding
between friction and adhesion force, tribology has been developed into an active research field. In
particular, in the pharmaceutical industry, the application of lubrication or tribology in drug development
has become increasingly important for developing a successful manufacturing process [2].
For pharmaceutical operations such as blending, roller compaction, tablet manufacturing, and
capsule-filling, lubrication is essential in order to reduce the friction between the surfaces
of manufacturing equipment and that of organic solids as well as to ensure the continuation of an
operation [3]. Pharmaceutical lubricants are the agents added to tablet and capsule formulations in a very
small quantity (usually 0.25%–5.0%, w/w) to improve the powder processing properties of formulations.
Albeit a fairly small amount, lubricants play important roles in manufacturing; they decrease friction at
the interface between a tablet’s surface and the die wall during ejection so that the wear on punches and
dies are reduced; they prevent sticking of tablets to punch faces as well as sticking of capsules to
dosators and tamping pins. In terms of powder flow, lubricants can improve the flowability of blends and
aid unit operations. For instance, for the blending of active pharmaceutical ingredients (APIs) of small
particles with other excipients, the adhesion force between particles can significantly reduce the powder
flowability by increasing inter-particle friction; poor flow can cause insufficient mixing of the blends
(content uniformity) and rat-holing in the hopper of a tablet press (segregation issue), impacting both
product quality and operation. To overcome these issues, lubricants are added (glidants) to enhance
powder flow by reducing the inter-particle friction. Regarding lubrication agents, although magnesium
stearate and stearic acid are the most frequently used lubricants in the pharmaceutical industry, there are
other lubricants in use as well [4]. Moreover, because technologies for monitoring the dynamics of
powder flow during manufacturing processes have been improved, the impact of lubricants on powder
dynamics and compact properties are now better understood. All of this will be summarized in
this paper.
In this review, we first present some fundamental principles on lubrication in terms of action
mechanisms: friction reduction, friction and adhesion, and lubrication in pharmaceutical processes [5].
Then, a general overview on the use of lubricants in the pharmaceutical industry is provided.
Specifically, magnesium stearate as a common lubricant will be examined in detail. Since there are many
reviews on the lubricants of pharmaceutical uses, this review will concentrate on some new
developments, including the pseudo-polymorphic aspect of magnesium stearate, the impact of
magnesium stearate on compaction dynamics as well as the mechanical properties of compacts, and the
technology development of online monitoring. Furthermore, we will review some potential chemical
3. Lubricants 2014, 2 23
interactions of magnesium stearate and its impurities with APIs in formulations. Finally, we conclude by
presenting a general principle for selecting a lubricant for a pharmaceutical formulation.
2. Fundamentals of Lubrication
2.1. Friction
In general, lubrication is related to the reduction of friction. Contrary to the common belief, friction
was actually first studied by Leonardo Da Vinci, but it was wrongly credited to Amontons, which is
often referred to as Amontons’s law [6]. The essential part of this law is expressed in Equation (1)
μ
F F
(1)
where FII, μ, and F┴ are the force of friction proportional to the external load (F┴), the coefficient of
friction, and the normal force applied. In Equation (1), the following assumptions are made: The force of
friction is proportional to the applied load; the frictional force is independent of the apparent contact
area; the kinetics of friction is independent of the sliding velocity. Clearly, this is over-simplified. Since
Amontons’s law was derived from observing sliding wooden blocks, there is no consideration of
adhesion. Amontons’s law applies well to geometric or mechanic models that the interlock of surface
asperities predominately contributes to the force of friction; the role of lubricants in reducing the
frictional force is to fill these surface cavities. However, this model cannot account for adhesion forces
involved which is ubiquitous for pharmaceutical operations due to the fine size of APIs and other
excipients. Therefore, to understand the force of friction involved in pharmaceutical operations, a model
with the incorporation of adhesion force is more suitable.
2.2. Friction and Adhesion
In general, friction is almost always associated with adhesion. By definition, the energy of adhesion is
the energy required to break two dissimilar surfaces [6,7]. As expected, friction always increases with
the adhesion between surfaces. The relationship between the force of friction and adhesion is shown in
Equation (2)
γ
μ 2ε
δ
F F A
(1)
The first term in Equation (2) represents a contact friction, where FII, F┴, and µ, are the force of
friction, the applied normal force, and the coefficient of friction. The second term is the force involved in
the adhesion hysteresis between two contacting materials, where A, ε, Δγ, and δ are the area of contact,
the transferred coefficient, the difference of surface energy, and the elemental distance [6]. As noted in
Equation (2), the adhesion force involved in an adhesion hysteresis cycle strongly depends on the
contact between two surfaces, which has been well investigated. Among the investigations are two
notable theories, the Johnson-Kendall-Roberts (JKR) and Derjaguin-Muller-Toporov (DMP) models
that have been reviewed by other authors [8]. Although each model has its own merits, they both assume
a smooth surface contact with elastic deformation. Since, in practice, most of the surfaces of equipment
used are rough rather than smooth, the effect of surface roughness on adhesion needs to be considered.
4. Lubricants 2014, 2 24
Recent experimental results suggest that adhesion force decreases exponentially with surface roughness
as described in Equation (3).
0
σ/σ
ad ad
(σ) (0)
F F e
(2)
where Fad(0) and σ represent the initial JKR adhesion force and the surface roughness parameter,
respectively [5]. In addition, under compression, pharmaceutical powders may undergo a plastic
deformation due to particle fracture or the deformation of excipients, or both. In this case, the adhesion
force (F(δ)) for flat punch consists of forces from both plastic and elastic regimes as displayed in
Equation (4).
(δ) y
F P A C
(3)
where Py, A, and C are the force of adhesion per unit area, the area of contact, and an elastic component [6].
To reduce the frictional forces, (specifically the adhesion force), lubricants are incorporated into
formulations to reduce the contact between powder particles and equipment surfaces [9]. In the next
section, we will focus on the mechanisms of reducing these forces using lubricants.
2.3. Lubrication
In general, there are four lubrication mechanisms: hydrodynamic lubrication, elastohydrodynamic
lubrication, mixed lubrication, and boundary lubrication [1,5]. As their names implies, the former three
mechanisms are related to the usage of liquid lubricants to some extent. In the pharmaceutical industry,
boundary lubrication is the most common mechanism functioning in unit operations [2]. For boundary
lubrication, a lubricant typically forms layers/film between surfaces or at interfaces to reduce friction,
where the penetration of the lubricant into surface asperities occurs. Structurally, the lubricants
commonly used for boundary lubrication are long chain molecules with active end-groups such as stearic
acid and its metallic salts. The typical end-groups include: (1) –OH (long chain alcohol); (2) –NH2
(long chain amine); (3) –COOH (long chain fatty acids); and (4) metal ions such as Mg2+
. The molecules
with these end-groups can be readily adsorbed on the surfaces of metals or other particles to form an
oriented monolayer or multilayers. The layers formed prevent further contact between the intended
surfaces and powder particles. The efficiency of a boundary lubricant is measured by the extent to which
these films can mask the field of force of the underlying surface [1]. In other words, a lubricant film such
as the film of magnesium stearate needs to be sufficiently thick to cover the surface, typically a few
layers. In addition, the breaking down of the lubricant film plays a significant role so that the motion of
lubricated surface is facilitated. This will be illustrated by our discussion on the dihydrate of magnesium
stearate, which in general gives the best lubrication efficiency due to its layered structure.
2.3.1. Lubrication in Pharmaceutical Processes
To prepare solid dosage forms, many pharmaceutical operations, including blending, die-filling,
compaction, capsule-filling, and compression, are utilized in the pharmaceutical industry. In these
processes, friction occurs at either powder-tool interfaces or particle-particle interfaces. For the
interaction between powder particles and the wall of equipment, it is commonly called wall friction; for
the particle-particle interaction, it is termed as internal friction. In the following sections, we focus on the
5. Lubricants 2014, 2 25
fundamental aspects of friction reduction through lubrication for both wall friction and
internal friction.
2.3.1.1. Wall Friction
Wall friction is the friction between a bulk solid and a solid surface such as between powder particles
and the wall of a bin blender, where the bulk solid moves over the surface of the blender. To quantify
wall friction, the wall friction angle, φx, and the coefficient of wall friction, µ, are often used. They are
defined by the following Equations:
W
W
τ
μ
σ
and w
w
τ
φ arctan
σ
x (4)
where τw and σw are the wall shear stress and the wall normal stress [10]. The larger the wall friction
angle or the coefficient of wall friction, the greater is the wall friction. Although the wall friction angle is
an important parameter to consider, in this paper, our discussion will focus on the coefficient of wall
friction. In terms of boundary lubrication, the addition of a lubricant in formulations is to reduce the
coefficient of wall friction by forming a boundary layer. For example, in a tableting process, the coefficient
of friction is derived by the application of a force balance through integration (see Equation (6) and
Figure 1) [11].
zt zb
μ (ln σ lnσ )
4
D
kL
(5)
where D, L, σzt, and σzb are the diameter of a powder compact, the length of the compact, the axial stress
on the top, and the axial stress on the bottom, and k is the ratio of radial stress (σr) over vertical
stress (σz).
Figure 1. Stress balance and the lubrication coefficient for powders in a tablet die: σua and σla
are stresses from top and bottom; τar is the shear stress.
6. Lubricants 2014, 2 26
In this case, lubricants are used to reduce the shear stress required to move a tablet out of a die
for a given normal stress. Similarly, lubricants can be used to decrease the internal friction among
powder particles.
2.3.1.2. Powder Flow
Flowability of a bulk solid is characterized mainly by its unconfined yield strength, σc, as a function
of the consolidation stress, σl. Usually, flow-function (ffc), which is the ratio of the consolidation stress,
σl, to the unconfined yield strength, σc, is used to characterize the flowability of a blend numerically:
ffc < 1, not flowing; 1 < ffc < 2, very cohesive; 2 < ffc < 4, cohesive; 4 < ffc < 10, easy-flowing; 10 < ffc,
free-flowing [10]. Poor flowability of powders in a hopper means that flow obstruction due to arching
occurs or uneven flow causes ratholing. In addition, poor flowability can also cause content uniformity
concern because of insufficient mixing. To improve the flowability of powders, flow aids or lubricants
such as magnesium stearate are often incorporated in formulations. Flow agents are used to enhance the
flow behavior of solids by reducing the inter-particle adhesion force. To achieve this, a flow agent
should adhere to the surface of particles of solids as shown in Figure 2. More or less, the role of flow
agent particles is similar to that of an increased surface roughness, in which the adhesion force is reduced
due to the increased distance between particles. In addition, in the case of magnesium stearate, the
hydrophobicity of the material surface also plays a role. As shown in Figure 2, the adhesion force of
powders with flow agents first decreases with the radius of flow agent particles followed by a minimum.
Then, it increases with the radius of particles. The optimal radius for reducing the inter-particle
adhesion force is approximately in the range of 5–50 nm as calculated, depending on the particles size of
powders [12].
Figure 2. Adhesive force (FH) as a function of the radius (r) of a flow agent for powder
particles with a radius of R.
3. Common Lubricants Used in Drug Development
As described before, most of the lubricants used in the pharmaceutical processes are boundary
lubricants; certainly, metallic salts of fatty acids such as magnesium stearate and stearic acid are the most
7. Lubricants 2014, 2 27
common ones. However, there are other lubricants, including fatty acid esters, inorganic materials,
and polymers, which can be used in the cases when both magnesium stearate and stearic acid do not meet
their performance expectation [13]. So, in the next section, various pharmaceutical lubricants other than
magnesium stearate and stearic acid will be briefly discussed.
3.1. Metallic Salts of Fatty Acids
Use of the metallic salts of fatty acids as lubricants has a long history in the pharmaceutical industry
and they are still the most dominant class of lubricants. Magnesium stearate, calcium stearate, and zinc
stearate are the three common metallic salts of fatty acids used and their chemical structures are shown in
Figure 3 [14]. Of these three lubricants, magnesium stearate is one of the most frequently used,
and its application will be discussed in the following sections. In this section, we concentrate on the
fundamental aspects of metallic salts of fatty acids in terms of friction reduction. Relative to fatty acids
including lauric, myristic, palmitic, and stearic acids—they are typically melted at low temperatures
(stearic acid has the highest melting point of about 69 °C), the metallic salts of fatty acids have much
higher melting temperatures: zinc stearate (120 °C), magnesium stearate (140 °C), and calcium stearate
(160 °C). In terms of the effect of chain length on friction reduction, typically friction decreases with
increasing length of the hydrocarbon chains; approximately, the coefficient of friction can be reduced
from about 0.5 to about 0.1. All in all, stearic acid has a chain length of the desired friction coefficient
reduction. In addition, temperature has little effect on lubrication until it reaches the melting points of the
lubricant. Furthermore, the structure of a lubricant layer at metal surfaces also plays a role in friction
reduction; a thick layer can maintain and sustain a friction reduction with time. However, use of too
much lubricant in tablet formulations can impact the product performance by decreasing tablet
dissolution. In summary, most of the metallic salts of fatty acids can reduce the coefficient of friction to
about 0.1. Nonetheless, other factors such as chemical compatibility will influence their use in the
pharmaceutical industry. In the following sections, we will discuss a few classes of fatty acids/salts of
fatty acids lubricants.
Figure 3. The chemical structures of metallic salts (calcium, magnesium, and zinc) of
stearic acids.
CH3 (CH2)16 C
O
O Zn
CH3
(CH2)16
O
C
O
Mg
Ca
3.2. Fatty Acids
Fatty acids are also common lubricants used in the pharmaceutical industry with stearic acid as the
most popular one. Chemically, stearic acid is a straight-chain saturated monobasic acid found in animal
fats and in varying degrees in cotton seed, corn, and coco [14]. The commercial material of stearic acid
has other minor fatty acid constituents such as myistic acid and palmitic acid. Depending on the
proportion of various acids present, the physical structure of commercial materials of stearic acid can
range from macrocrystalline to microcrystalline. Correspondingly, its material properties can vary from
8. Lubricants 2014, 2 28
hard, to brittle, quite soft, and crumbly. For the macrocrystalline form of stearic acid, it has a ratio of
stearic acid to palmitic acid of 45:55 (w/w); for the microcrystalline form, the ratio for stearic acid to
palmitic acid is between 50:50 and 90:10. Table 1 shows the physical properties of these acids. As shown
in Table 1, stearic acid has the highest melting and boiling points of the three. In addition, the lubrication
property of stearic acid is listed in Table 2. Table 2 summarizes the friction coefficient, breakdown
temperature-transition temperature from solid to liquid-of stearic acid at various metal surfaces.
As shown in Table 2, the measured coefficient of friction varies with different metal surfaces
(including steel), but their values are close to 0.1, similar to those reported for the metallic salts of fatty
acids [1]. Therefore, it is expected that the lubrication performance of stearic acid should be similar to
that of magnesium stearate at metal surfaces.
Table 1. Physical properties of pure solid fatty acids.
Fatty acid Formula Molecular weight Melting point (°C) Boiling point at 16 mm (°C)
Stearic CH3(CH2)16COOH 284 69.6 240
Palmitic CH3(CH2)14COOH 256 62.9 222
Myristic CH3(CH2)12COOH 228 54.4 202
Table 2. Breakdown temperatures and friction coefficients at various metal surfaces.
Surfaces Lubricant
Coefficient of
friction at 20 °C
Breakdown
temperature (°C)
Copper
1% stearic acid
Smear copper stearate
0.08, smooth
0.08
90
94
Platinum & cadmium
1% stearic acid
Cadmium stearate
0.05
0.04
130
140
Platinum & steel Smear sodium stearate 0.1 280
3.3. Fatty Acid Esters
Fatty acid esters, including glyceride esters (glyceryl monostearate, glyceryl tribehenate, and glyceryl
dibehenate) and sugar esters (sorbitan monostearate and sucrose monopalmitate), are often used as
lubricants in the preparation of solid dosage forms [13,15,16]. Glyceryl dibehenate (Compritol®
888
ATO) is the one commonly used [17]. In particular, Compritol®
888 ATO is an effective lubricant to
replace magnesium stearate when the latter causes delay of dissolution and other compatibility issues.
Relative to magnesium stearate, Compritol®
888 ATO has similar lubrication efficiency with a higher
optimal concentration (around 2%, w/w). In addition, the use of Compritol®
888 ATO does not affect
compressibility. Furthermore, when a hot-melt coating process is used, the optimal concentration of
Compritol®
888 ATO can be reduced to 0.5%–1% due to the reason that a uniformed coating is
obtained [17].
3.4. Inorganic Materials and Polymers
Inorganic materials and polymers are also used as lubricants when magnesium stearate is not
appropriate [2,13]. In terms of inorganic materials, talc (a hydrated magnesium silicate (Mg3Si4O10(OH)2)),
is often used as a lubricant or a glidant in formulations [18]. Talc provides some essential lubricity for
9. Lubricants 2014, 2 29
pharmaceutical operations because of its hydrophobicity and weakly-bonded sheet structure. Compared
with magnesium stearate, talc is less efficient in lubrication. However, when the formulation lubricated
with magnesium stearate exhibits compatibility issues such as dissolution slow-down, talc can be used as
a replacement or in combination with magnesium stearate. In many cases, the use of talc as a lubricant in
formulations can improve tablet hardness, friability, and appearance. Similarly, polymers, such as PEG
4000, are occasionally used as lubricants in solid dosage forms when the use of magnesium stearate
displays compression and chemical incompatibility issues [19]. Overall, as mentioned before,
magnesium stearate is still the principal lubricant used in the pharmaceutical industry. In the following
discussion, we will focus our attention on the effect of magnesium stearate on process and product
performance, including the effect of its pseudo-polymorphic properties on lubrication, the impact of
powder properties on blend flowability, and the influence of lubrication on compaction/compression
dynamics and the mechanical properties of compacts and tablets, as well as its incompatibility with APIs
and other formulation components.
4. Magnesium Stearate
Magnesium stearate (Mg(C18H35O2)2) is a solid and white powder at room temperature; it is a Food
and Drug Administration (FDA)-approved inactive ingredient commonly used in the pharmaceutical
industry. Magnesium stearate may be derived from plants as well as animal sources. It is prepared either
by the chemical reaction of an aqueous solution of magnesium chloride with sodium stearate, or by the
reaction of magnesium oxide, hydroxide or carbonate with stearic acid at elevated temperatures. The raw
materials used in the manufacturing of magnesium stearate are refined fatty acids, a mixture of palmitic
and stearic acid. Due to its manufacturing process, there are various impurities in magnesium stearate,
often causing incompatibilities with APIs. So the chemical instability of APIs in the presence of
magnesium stearate and their incompatibility, caused by either magnesium stearate or its impurities such
as magnesium oxide, will be discussed in the chemical stability and incompatibility section. In the next
few sections, our focus will center on the effect of magnesium stearate on the manufacturing process and
product performance.
4.1. Effect of Pseudo-Polymorph [20,21]
Magnesium stearate can form a variety of hydrates upon exposure to humidity. In addition to
amorphous, magnesium stearate possesses four hydration states: anhydrate, monohydrate, dihydrate,
and trihydrate. These hydration states can interchange reversibly, depending on temperature and relative
humidity (RH). For instance, the trihydrate of magnesium stearate could be generated by exposing its
anhydrate to a RH >70%. Therefore, depending on the environment in which materials have been
exposed, magnesium stearate obtained from a vendor can be a mixture of anhydrate, hydrates, and
amorphous. Consequently, most of the commercial supplies for this lubricant contain a mixture of
various hydrates in unknown ratios. As reported, the lubrication efficiency of magnesium stearate as a
lubricant varies from one hydration state to another; in general, the dihydrate is considered to be the most
efficient lubricant of all, due to its crystal structure which is suitable for shearing. As a result, the
flowability, permeability, porosity, and compressibility of a particular formulation lubricated with
magnesium stearate depend on its moisture content or the RH of storage conditions. To further
10. Lubricants 2014, 2 30
investigate the impact of the hydration state of magnesium stearate on the performance of formulations,
each hydrate was isolated and tested in formulations. For example, to test the lubrication efficiency of
each hydrate and their mixtures, each hydrate or a combination of two (1%, w/w) was mixed with other
formulation components: MCC (72%, w/w), lactose monohydrate (22%, w/w), and acetaminophen
(5%, w/w). In general, different hydration states produce varied effects on the performance of
formulations. For example, the formulation lubricated with the monohydrate of magnesium stearate
showed the lowest permeability and porosity followed by the formulations lubricated with the dihydrate
and the anhydrate of magnesium stearate, and finally the un-lubricated formulation. This suggests that
the structure of the lubricant affects the inter-particle packing arrangement, and consequently the blends
containing the monohydrate require a higher pressure to establish a flow relative to those with the
dihydrate and the anhydrate. However, in terms of the crush strength of compacts, the un-lubricated
formulation produced compacts with the highest crush strength (15.471 kg/cm2
) followed by the
formulations containing the dihydrate, the monohydrate, and the mixture of (50:50, w/w) the dihydrate
and the monohydrate. Regarding lubrication, lubricity index—a measure of over-lubrication-can be
expressed as: (σcunlubricated − σclubricated)/σcunlubricated, where σcunlubricate and σclubricated are un-lubricated and
lubricated crush strengths for compacts; the formulation containing the dihydrate showed the least
tendency to cause over-lubrication. Thus, the lubricity index-ranking for the tendency to cause
over-lubrication at a fixed concentration and lubrication time was: the dehydrate < the monohydrate <
binary mixtures < the anhydrate. These results suggest that the level of water of hydration in the
lubricant influences the tendency of over-lubrication. Furthermore, considering the effect of the
hydration state on the compression process (pre-compression, main compression, ejection, and total
forces), all blends containing the monohydrate yielded compression forces with less variability. In fact,
the compression force profiles of the blends with the binary mixtures of the monohydrate and dihydrate
or anhydrate were similar to those using the monohydrate alone, suggesting that the monolithic structure
of the monohydrate of magnesium stearate appears to be the dominant influence in achieving a stable
compression force. Further results indicated that the blends with either the anhydrate or the dihydrate
required less total force for compression. Moreover, the blends containing the binary mixtures of the
dihydrate with the anhydrate in various ratios seemed to require less total force than those with the
dihydrate and the monohydrate, suggesting that the presence of the monohydrate in formulations
requires more ejection force. In summary, when comparing the performance of three hydrates of
magnesium stearate and their binary combinations (ratio varied from 25:75, 50:50 to 75:25), the
formulations containing the monohydrate tend to have less permeability and porosity, and these
formulations produce tableting forces with less variability during operation. However, they in general
require more ejection force. In contrast, relatively, the formulations lubricated with the dihydrate appear to
have less tendency for over-lubrication and require less total compression force. Overall, the performance
of formulations having the dihydrate form of magnesium stearate is superior to others (see Table 3 for
detailed ranking). Fundamentally, it is generally believed that the long spacing in the crystal structure of
magnesium stearate dihydrate contributes to its lubrication efficiency although it has been suggested that
the determination of the exact spacing for these forms is challenging due to the reversible exchange of
water between forms. Finally, in addition to its pseudo-polymorphic effect on lubrication, the powder
properties or the solid properties of magnesium stearate such as particle size, particle morphology, and
11. Lubricants 2014, 2 31
surface area also influence the lubrication performance of formulations with magnesium stearate, and
this will be discussed in the following section.
Table 3. The overall performance ranking of three pseudo-polymorphs of magnesium
stearate and their binary mixtures [20].
Formula
Magnesium
stearate ratio
Pre-Compression
force
Main compression
force
Ejection
force
Porosity Overall ranking
1 A50:M50 F F P P 12th
2 A25:M75 P G P P 11th
3 A75:M25 P G F F 5th
4 D50:A50 P G G G 5th
5 D75:A25 F G G G 3rd
6 D25:A75 F P G G 4th
7 D50:M50 F P P F 8th
8 D75:M25 F F F P 8th
9 D25:M75 F F F P 8th
10 Anhydrous G F G F 2nd
11 Monohydrate F P P P 7th
12 Dihydrate G F G F 1st
A, M, and D represent anhydrous, monohydrate, and dihydrate; P, F, and G stand for poor, fair and good.
4.2. Effect of Powder Properties on Lubrication
In practice, the effect of the hydration state of magnesium stearate on lubrication cannot be separated
from other factors such as surface areas and agglomeration [22]. The materials of magnesium stearate
obtained from various vendors or different batches of the same vendor often have varied powder
properties such as particle size, surface area, and particle shape [23]. Therefore, it is important to
understand the impact of these properties on the performance of the lubricated formulations, including
the mechanical properties of the compressed products, the dissolution of tablets, and the flowability of
powder. Generally, it is expected that the lubrication efficiency of magnesium stearate improves with
increasing its surface area or decreasing its particle size since the increase of surface area can provide
more surface coverage [24]. Consequently, with more coverage of particle surfaces by magnesium
stearate, the particle-particle bonding is weakened, resulting in weak tablets. In addition, because the
surface of API particles is covered with the lubricant which is hydrophobic, it causes slow-down of
dissolution. For instance, as reported by Dansereau and Peck [25], the tensile stress of MCC tablets
lubricated with magnesium stearate decreased with increasing surface area of the lubricant. As a result,
the friability of these tablets went up with increasing the surface area. Additionally, it was reported that
the dissolution of dexamethasone-lactose tablets was enhanced by increasing the particle size of
magnesium stearate, and the optimal size range for the lubricant was found to be from 350–500 μm [26].
More recently, the impact of the variability of powder properties of magnesium stearate on the
roller-compacted, immediate release tablets was investigated based on a quality-by-design study [27]; in
addition to the lubricant, MCC, spray-dried lactose, and sodium starch glycolate were also included in
the study. Particularly, the effect of the variability of the lubricant on formulation performance such as
the flowability of blends, segregation propensity, hardness, and tensile strength was evaluated. It was
12. Lubricants 2014, 2 32
concluded that the ribbon tensile strength and tablet hardness significantly increased as the specific
surface area of magnesium stearate decreased (particle size increased), which is consistent with the
results reported previously.
The flowability of blends in pharmaceutical operations is critical for the success of manufacturing.
Since the addition of magnesium stearate in a formulation generally improves the flowability of the
formulation, it is often used as a flow agent. The flowability of a blend is typically assessed by
measuring the following parameters: static angle of repose, Carr index, Hausner ratio, and the
flow-function obtained from a shear-cell measurement. Of these parameters, the flow-function is the
most useful parameter for assessing blend flowability, but other parameters are often used because of
their simplicity. In general, the flowability of a blend is affected by many factors: the type of lubricant,
the interaction of the lubricant with other materials, lubricant concentration, and mixing time. For
example, relative to other lubricants including magnesium silicate, calcium stearate, and stearic acid,
magnesium stearate is the most effective lubricant in improving the flowability of lactose even with a
small amount [28]. This is because the particles of magnesium stearate preferentially interact with
lactose particles and fill the surface cavities of these particles. The impact of magnesium stearate on the
flowability of a blend also depends on the material nature of the blend. For instance, for a free-flow
blend, the effect of the lubricant on the blend flowability is not significant. However, as the blend
becomes more cohesive, the presence of lubricant greatly improves its flowability [29]. In addition, the
flowability of the blends containing an API is also related to the API particle size and size distribution.
As an example, the flowability of ibuprofen particles of various sizes was shown to be significantly
improved by lubrication using magnesium stearate based on internal angle measurement [30]. This can
be explained by the fact that small particles (fines) of APIs typically cause a flow issue, and the
incorporation of the lubricant as a flow agent can coat the surface of particles to reduce inter-particle
friction, which ultimately improves the powder flow. For a lubricant to be effective as a flow agent, it
needs to adhere to the surface of particles. Thus, distribution of the lubricant throughout blends by
mixing is critical. However, over-mixing often causes dissolution delay or other issues. As shown in a
study, for a mixture of lactose and magnesium stearate, when it was mixed beyond the optimal time
(a few minutes), the performance of tablets decreased; the hardness of tablets was reduced, and the
disintegration time was prolonged. This is because once magnesium stearate delaminates and forms a
film around substrate particles, it is very difficult to disrupt. Furthermore, the distribution of magnesium
stearate among substrate particles and its film formation around the substrate particles is also dependent
on the mixing speed and the equipment used as shown by the study [31]. Mechanistically, the mixing
behavior of magnesium stearate is governed by shear, as well as dispersion and convective actions, and
shear mixing has been proven to be the most important of the three [32]. Since magnesium stearate is
fairly hydrophobic, its mixing behavior is similar to that of sodium dodecyl sulfate. Finally, magnesium
stearate can be combined with other additives such as silicon dioxide to further improve the flowability
of micronized APIs. In conclusion, magnesium stearate is an effective agent to improve the flowability
of APIs and formulations.
13. Lubricants 2014, 2 33
4.3. Effect on the Mechanical Properties of Compressed Products [33–35]
As discussed before, the presence of magnesium stearate in a blend can significantly affect the
flowability of the blend, which consequently impacts on the dynamics of compaction/compression
processes (such as roller compaction). Therefore, the mechanical properties of any compacts/tablets
manufactured are lubricant dependent. For instance, during the roller compaction of the blends of
microcrystalline cellulose (MCC) and dicalcium phosphate dihydrate (DCPD), the presence of
magnesium stearate modified the compaction dynamics by influencing both the maximum compression
pressure and the nip angle of the process. Specifically, comparing the blend of MCC lubricated with
magnesium stearate with that without, both the maximum compression pressure and the nip angle were
reduced with lubrication at roll speeds of 3 rpm as well 5 rpm. Additionally, the reduction of the
maximum compression pressure and the nip angle increased with increasing lubricant concentration. In
terms of the method of lubrication, it was found that mixing the lubricant with MCC powders
(bulk-lubrication) was much more effective than just spraying the lubricant to press surfaces
(roll-lubrication). Furthermore, since lubrication reduced the compression pressure and the nip angle,
the mechanical properties of compacts such as density were also altered. In particular, relative to the
MCC blend without lubricant, the relative density of the lubricated ribbon, compressed from the MCC
blend containing magnesium stearate, was consistently lower. This is because the compression pressure
for the lubricated blend is generally lower compared with the un-lubricated one, due to the improved
flowability and the reduction of wall friction. As expected, the average relative density of the ribbons
remained unaffected when just the press was lubricated by spraying; this is due to the fact that
roll-lubrication only reduces the friction between powders and the surface of a compactor, not the
inter-particle friction of powder particles. However, for DCPD blends, a brittle material, the maximum
compression pressure and the nip angle were reduced by both roll-lubrication and bulk-lubrication; the
values of reduction were comparable for both, reaching a constant value at 0.25% (w/w) lubricant
concentration. The reason for the difference between MCC and DCPD blends is that DCPD powders are
brittle (easy to fracture) and less cohesive relative to MCC powders. Therefore, the flowability of DCPD
powders is dominated by new surfaces generated by particle fracture so that its effect on the compression
pressure and the nipple angle is about the same, whether roll-lubrication or bulk-lubrication.
Lubrication also affects the solid fraction of ribbons after compaction as well as the solid fraction and
the tensile strength of tablets made. In this case, for the ribbons prepared with MCC blends, the reduction
of the solid fraction increased with the lubricant concentration for both bulk-lubrication and
roll-lubrication; relatively, bulk-lubrication yielded a larger reduction. In addition to the reduction of the
solid fraction, the fracture energy for MCC ribbons was also reduced. Interestingly, a similar trend was
observed for the ribbons made from DCPD blends although the solid fraction of DCPD ribbons was
smaller than those made with MCC blends. Besides, the ribbons of DCPD were too fragile for measuring
the fracture energies. Overall, the ribbon density is determined by how powder is fed into the
compaction zone, which is influenced by the flowability of the powder. In terms of operating parameters
including the nip angle and the maximum pressure in the nip region as well as the variation in density
across a ribbon, they often increase with increasing friction, and therefore, these parameters would
decrease if the powder were to be lubricated.
14. Lubricants 2014, 2 34
When a uniaxial compression process is used to make tablets, lubrication impacts the properties of
tablets whether powders or granules are used as feeding materials. In the case of MCC, the solid fraction
of MCC tablets was not affected by lubrication, but their tensile strength was reduced, in particular at
1% magnesium stearate concentration; this was true whether the powders of MCC or the granules of
MCC were fed into the tablet press; however, relative to the tablets made from feeding MCC powders,
tablets have a lower solid fraction and tensile strength when MCC granules are used. For DCPD tablets,
the solid fraction and tensile strength were not affected with lubrication for both feeding materials.
However, in general, the tablets made with DCPD granules have much lower tensile strength. This is
because MCC is a deformable material whereas DCPD is a brittle material. Mechanistically, the
reduction of tensile strength for MCC tablets is due to magnesium stearate, a boundary lubricant, which
coats the particle surface to form a layer and reduces the tablet strength. Interestingly, for DCPD, it
appears that lubrication with magnesium stearate has little effect on both the solid fraction and the tablet
strength, primarily because the fractured-nature of DCPD creates fresh surfaces without lubricant
attached, so that the tablet strength is not affected.
4.4. Online Monitoring of Magnesium Stearate in Blending
As discussed above, lubrication can significantly change the dynamics of blending and
compaction/compression, as well as the mechanical properties (solid fraction and tensile strength)
of compacts/tablets made. Therefore, monitoring of the change of magnesium stearate during
manufacturing and storage becomes very critical. In particular, the hydration state of magnesium
stearate changes with humidity and temperature, and its lubrication efficiency varies with its
composition. To detect the composition change, near infrared spectroscopy (NIR) in conjunction with
other thermal methods was used to monitor the variability of the hydration state during operation, in
which the absorption wavelengths for monohydrate and dehydrate are 7045 and 5100 cm−1
,
respectively [36]. The results from NIR were in general consistent with those obtained using other
methods such as thermal gravimetric analysis. However, the NIR method with partial least squares
regression analysis is more sensitive to the presence of small quantities of hydrates. In addition, the
distribution of magnesium stearate on tablet surfaces in a punch-face lubrication system was detected by
Raman imaging technique using a wavelength of 1295 cm−1
, allowing the determination of the domain
size of magnesium stearate in one dimension [37]. In contrast, when the same approach was applied to
lubricated formulations, Raman failed to detect the signal of magnesium stearate presumably due to
interferences from other materials in the formulations. Furthermore, to determine the end-point of a
blending process for a formulation with magnesium stearate, thermal effusivity sensors can be used to
monitor the blend uniformity [38]. This was demonstrated for the blend of magnesium stearate and sugar
sphere in a V-blender. Comparing the thermal effusivity data with the powder density, the former
correlated well with the powder characteristics of the system for achieving optimal mixing. This is
important since when various hydrates of magnesium stearate are used as lubricants, the time required to
achieve a homogeneous blend varies. Hence, using thermal effusivity sensors to monitor a blending
process can detect the end-point nondestructively without sampling the blend to avoid over-lubrication.
Overall, the online monitoring of pharmaceutical processes becomes increasingly important for
15. Lubricants 2014, 2 35
achieving the optimum performance for a formulation and avoiding the detrimental effect due to
over-lubrication and inhomogeneous distribution.
5. Chemical Stability and Compatibility
Chemical instability issues of APIs in the presence of lubricants have been widely reported,
especially for magnesium stearate. Regarding the effect of magnesium stearate on the chemical
instability of an API, there are several factors to consider, including the impurities (MgO), the effect of
alkalinity caused by magnesium stearate, its catalytic effect, and other chemical reactions initiated and
mediated by magnesium ions. These will be discussed in the following sections.
5.1. Potential Interactions with Impurities (MgO)
The commercial materials of magnesium stearate contain several impurities such as magnesium
oxide (MgO) and palmitic acid; so, these impurities often react with APIs in the solid state causing
stability issues. For instance, as reported by Kararli et al., MgO reacts with ibuprofen at certain
temperatures and humidity values in the solid state [39]. Specifically, when the mixture of MgO and
ibuprofen was stressed at 40 °C and 75% RH, a significant amount of degradation was detected by
differential scanning calorimeter (DSC), thermal gravimetric analysis (TGA), and multiple internal
reflectance infrared (MIR). In fact, MgO reacted with ibuprofen to form the magnesium salt of
ibuprofen. The reaction was accelerated with increasing temperature; it degraded at 40 °C after 1 day;
but at 30 °C, no significant interaction was observed for up to 80 days. In another study, ketoprofen was
found to form a eutectic mixture with magnesium stearate [40,41]. Besides, the magnesium stearate
itself also reacts with APIs, and a few examples are given in the following passage.
5.2. Hydrolytic Degradation at Basic pH
The presence of magnesium stearate in a formulation can increase the micro-environmental pH of the
formulation, creating an alkaline condition and consequently accelerating the hydrolysis of some drugs.
For example, the degradation rate of acetylsalicylic acid (aspirin) in a blend increased with the addition
of magnesium stearate; the hydrolysis rate depended on the concentration of magnesium stearate in the
blend. This is because acetylsalicylic acid is a moisture-sensitive drug, and its degradation is often
associated with the presence of water and/or an alkaline pH condition [42–44]. In addition, Kornblum
and Zoglio [45] found that in the presence of magnesium stearate, the rate of degradation of
acetylsalicylic acid in suspensions was associated with the high solubility of the magnesium salt of
acetylsalicylic acid. Presumably, this is due to the fact that a buffer layer around the particles of
acetylsalicylic acid was formed, creating an environment that was detrimental to the chemical stability
of the compound [46]. Based on Miller and York’s [13] description, the lowering of the melting point of
acetylsalicylic acid may be facilitated by the formation of a surface film of magnesium stearate around
the particles of acetylsalicylic acid, creating intimate contact between the two materials and leading to
degradation. As a consequence of chemical incompatibility between aspirin and magnesium stearate, a
number of potentially undesirable products, such as salicylic acid, salicyl salicylic acid and acetyl salicyl
salicylic acid, are produced. Furthermore, the presence of MgO impurity in magnesium stearate may
16. Lubricants 2014, 2 36
also play a role since it could enhance the degradation by creating an alkaline pH environment. For
example, Gordon et al. noticed that in the presence of magnesium stearate, ibuprofen forms a eutectic
mixture which sublimates [47]. Additionally, quinapril (a tetrahydroisoquinoline carboxylic acid), an
angiotensin-converting enzyme (ACE) inhibitor, was also found to be incompatible with magnesium
stearate due to the basicity of the lubricant; the degradation of quinapril was mediated by the availability
of moisture. However, on the positive side, as reported by Fouda et al., although magnesium stearate
accelerated the degradation of aspirin, stearic acid can protect drugs (aspirin) against degradation [44].
Therefore, for this reason, stearic acid is an alternative option in terms of lubricant selection. Finally, in
addition to hydrolysis, oxidation is another reaction causing chemical instability issues associated with
the presence of magnesium stearate, which is discussed in the next section.
5.3. Oxidation
The presence of magnesium stearate in a formulation can also induce an oxidation reaction. For
instance, the decomposition of drotaverine HCl was accelerated when magnesium stearate and talc were
present in a formulation [48]. In addition, the chemical instability of drotaverine hydrochloride was
significantly influenced by the pH of the formulation, and the degradation rate was largely enhanced in
the presence of magnesium stearate. Specifically, drotaverine HCl was degraded to drotaveraldine by an
oxidative degradation pathway, which can be inhibited using an antioxidant or an acidic auxiliary
material. A similar catalytic action of magnesium stearate was observed with the autoxidation
of 2,6,10,14-tetramethylpentadecane, where magnesium stearate catalyzed the decomposition of
hydroperoxide first to boost autoxidation of the compound [49]. Aside from its effect on oxidation, the
metal ions from magnesium stearate also cause chemical instability.
5.4. Metal Ion-Mediated Degradation
Degradation of drugs is also mediated by the presence of magnesium ions. For example, upon an
accelerated stress treatment, fosinopril sodium was degraded into a β-ketoamide (III) and a phosphoric
acid (IV) in a prototype tablet formulation with magnesium stearate [50]. It was shown by further
investigation that the degradation of fosinopril was mediated by magnesium metal ions, and thus a
mechanism invoking metal chelation was postulated. Based on a kinetic study, it was established that the
degradation was a second-order reaction between fosinopril and magnesium. Since many drugs are
susceptible to ion-catalyzed degradation, it has been suggested that stearate salts should be avoided as
tablet lubricants. However, by addition of malic acid, hexamic acid, and maleic acid in a formulation, the
degradative effect of alkali stearates can be inhibited due to competition for the lubricant cation between
the drug and an additive acid. The incompatibility of magnesium stearate with a drug also depends on the
functional groups of the drug. For example, drugs with an amine group are often very reactive, which is
discussed in the following section.
5.5. Reaction with Amines
Many drugs contain amine groups, and amines are typically prone to reactions with excipients and
salt counter-ions. Specifically, the potential for a reaction with magnesium stearate or stearic acid is
17. Lubricants 2014, 2 37
particularly of concern when a drug has a primary amine group. In the case of norfloxacin, after a
prolonged storage at 60 °C, the formation of a stearoyl derivative was observed in the tablets containing
magnesium stearate. Other drugs, found to be incompatible with magnesium stearate, include
glimepiride, cephalexin, glipizide, ibuproxam, indomethacin, ketoprofen, moexipril, nalidixic acid,
primaquine, promethazine hydrochloride, temazepam, glibenclamide, penicillin G, oxacillin,
clopidogrel besylate and erythromycin [51]. In summary, drugs with a primary amine group are often
very unstable in formulations containing magnesium stearate. Besides the reaction associated with a
primary amine group, the incompatibility between magnesium stearate and drugs can be caused by other
interactions as well, which is described in the following section.
5.6. Other Interactions between Magnesium Stearate and Drugs
There are other interactions between drugs and magnesium stearate causing incompatibility.
Captopril (another ACE inhibitor) is a pyrrolidine carboxylic acid derivative used in the treatment of
hypertension. During grinding (5 min at room temperature at 32% or 80% RH), it was shown that
captopril interacted with a metallic stearate at surfaces, in which the mixtures of captopril and each
metallic stearate gave different results, before and after grinding, as detected by differential scanning
calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transformed infrared spectroscopy
(FTIR). It appeared that grinding accelerated the solid-state interaction of captopril with magnesium
stearate. In addition, the solid-state interaction between captopril and magnesium stearate was also
evidenced by the shifting of the IR spectral peak for the –COOH of the stearate moiety from
1578–1541 cm−1
. This can be attributed to the interaction of the –OH group in the carboxylic acid of
captopril with bridging coordination of the –COO group of magnesium stearate via hydrogen bonding
involving water; the interaction between captopril and magnesium stearate was stopped at 60 °C due to
evaporation of water from the ground mixture.
Other interactions between lubricants and drugs also affect the performance of drug products. For
example, as described before, prolonged mixing of formulations with magnesium stearate can result in
slow-down of dissolution due to the excessive coating of granules by magnesium stearate, which acts as
a water repellant. The extent of slow-down in the dissolution of formulations may depend upon the
aqueous solubility of the active ingredients. This phenomenon was also observed for other hydrophobic
lubricants such as calcium stearate or zinc stearate. However, when replacing magnesium stearate with
hydrophilic lubricants such as Stear-O-Wet®
or sodium stearyl fumarate, the dissolution slow-down was
not observed. Similarly, changing a disintegrant can also improve the dissolution of formulations. For
instance, Desai et al. studied the effect of magnesium stearate on the content uniformity of three APIs in
powder blends [52]. Among the hydrophobic lubricants, magnesium stearate caused the maximum
slow-down in dissolution, followed by zinc stearate and calcium stearate, respectively. Replacement of
pregelatinized starch by starch-derived superdisintegrants such as Explotab®
or Primojel®
resulted in no
slow-down of the dissolution of capsules, even after over-mixing with 1% w/w magnesium stearate.
Interestingly, although the granules over-mixed with 1% w/w, hydrophobic lubricants exhibited
slow-down in dissolution when filled into capsules, tablets compressed from these granules dissolved
rapidly, indicating the impact of dosage forms on dissolution. Besides magnesium stearate, stearic acid
and sodium stearyl fumarate are two common alternative lubricants used in pharmaceutical
18. Lubricants 2014, 2 38
formulations. Their lubrication properties and interactions with APIs are briefly reviewed in the
following sections.
5.7. Stearic Acid
Although stearic acid (12 out of 200 tablet formulations), in comparison with magnesium stearate
(108 out of 200 tablet formulations), is a less frequently used lubricant, it provides an important
alternative option when the use of magnesium stearate is not feasible. As reported by Desai et al., the
incompatibility of stearic acid with other formulation components is of concern [53]. For example, it was
observed that two formulations in capsules, containing povidone as a binder and stearic acid as a
lubricant, exhibited slow-down in dissolution, after 3–6 weeks of storage under elevated temperature
and humidity conditions [53]. Once stearic acid was replaced with magnesium stearate, a rapid
dissolution was obtained under similar storage conditions. On further investigation, it was shown that
the mixture of povidone and stearic acid formed a transparent, hard, glass-like insoluble substance at
50 °C. Because the porosity of granules was reduced by the glassy material formed, the dissolution of the
granules was slowed down. To further verify, powder X-ray diffraction was used to examine the mixture
of stearic acid and povidone, showing that stearic acid lost its crystallinity. Based on this observation, it
was suggested that a combination of stearic acid and povidone should be avoided for immediate release
formulations. In addition, as reported by Wang et al., stearic acid can also play a role in the polymorphic
phase transformation of an API, which subsequently results in slow-down of the dissolution of its
tablets [54]. Specifically, when formulations were subjected to high shear mixing or high temperature
drying, the dissolution slow-down was more significant. Mechanistically, it was found the slow-down of
tablet dissolution was due to the transformation of polymorphic forms (Form II to Form I), which was
facilitated by stearic acid [54]. In summary, even though stearic acid has incompatibility issues
with APIs or formulation components, it is still an important alternative lubricant to be used in solid
dosage forms.
5.8. Sodium Stearyl Fumarate
In addition to stearic acid, sodium stearyl fumarate is another alternative lubricant to be used in solid
dosage forms. Since sodium stearyl fumarate is often supplied in a purer form, it can provide an option
when the less pure stearate-type lubricants (stearic acid and magnesium stearate) are unsuitable due to
chemical incompatibility. Sodium stearyl fumarate has a usage rate of four out of 200 drugs as a
lubricant in formulations. It is less hydrophobic and has a less retardant effect on tablet dissolution than
magnesium stearate. As reported by Arne W. Hölzer, et al., compared with magnesium stearate, sodium
stearyl fumarate has the same lubrication efficiency, and about the same influence on tablet strength and
disintegration [55]. However, due to the importance of the particle size of sodium stearyl fumarate,
prolonged mixing improved its lubricating effect and had no effect on tablet disintegration. Therefore,
sodium stearyl fumarate appears to be a good alternative to magnesium stearate in certain solid
dosage formulations.
19. Lubricants 2014, 2 39
6. Considerations for Selecting a Lubricant
In summary, there are many factors to be considered for selecting an appropriate lubricant for
preparing solid dosage forms including: low shear strength, being able to form a durable layer covering
the surface/particles, non-toxic, chemically compatible with APIs and other components in the
formulation, low batch to batch variability, and having minimum adverse effects on the performance of
the finished dosage forms. In addition, the optimal concentration and mixing time are also needed to be
taken into consideration when selecting a lubricant because both of these two parameters greatly impact
the performance of pharmaceutical products and processes. Although low lubricant concentration and
inadequate mixing cause inefficient lubrication issues such as sticking, capping, and binding in the
die cavity, over-lubrication-high lubricant concentration and over-mixing-often results in an adverse effect
on products as well as processes, including the reduction of tablet hardness, compression variability, the
prolongation of disintegration time, and the decrease of the rate of dissolution. In Table 4, the
recommended concentrations of typical lubricants used in solid dosage forms are listed. In terms of the
process of adding a lubricant, the lubricant is often added at the end of the granulation process in the
outer phase when other components have been mixed thoroughly. Furthermore, the mixing time for
distributing a lubricant is typically 0.5–5 min for better results on compactability and the hardness of
tablets. Finally, selecting a lubricant for a formulation requires a systematic approach with careful
consideration of the performance of both product and process.
Table 4. The optimal concentration of commonly used lubricants for preparing solid
dosage forms.
Water soluble lubricant
Amount in
formulation (%)
Water insoluble lubricant
Amount in
formulation (%)
Boric acid 1 Metal (Mg, Ca, Na) stearate 0.25–2
Carbowax (PEG) 4000/6000 1–5 Stearic acid 0.25–2
Sodium oleate 5 Sterotex 0.25–1
Sodium benzoate 5 Talc 1–5
Sodium acetate 5 Waxes 1–5
Sodium lauryl sulfate 1–5 Stear-O-Wet 1–5
Mg-Lauryl sulfate 1–2 Glyceryl behenate (Compritol 888) 0.5–3
7. Conclusions
In this paper, the fundamentals of lubrication and the action mechanisms of lubricants in typical
pharmaceutical manufacturing processes have been reviewed; the role of lubricants in improving
pharmaceutical operations by reducing the adhesion forces between powder/equipment as well as
particle/particle in terms of wall friction and inter-particle friction has been summarized. In addition to
other classes of lubricants used in the pharmaceutical industry, magnesium stearate as the most
frequently used lubricant has been discussed in detail. Furthermore, the lubrication efficacy of hydrates
of magnesium stearate and their effect on the performance of formulations in pharmaceutical operations
were discussed. Overall, it was concluded that the dihydrate of magnesium stearate is the best hydration
state for lubrication. In terms of the effect of lubricant particle size, magnesium stearate with a large
20. Lubricants 2014, 2 40
surface area and small particle size has the best lubrication efficiency, but it reduced the hardness of
tablets and caused slow-down of dissolution. Moreover, the lubricant significantly affects the dynamic
process of compaction/compression and the mechanical properties (solid fraction and tensile strength) of
ribbons as well as tablets due to the improved flowability of the lubricated blends. For adequate
lubrication, on-line monitoring can help to determine the end-point of a blending process, and the
distribution of lubricant as well as its composition. Finally, magnesium stearate and its impurities often
cause chemical instability of APIs. In selection of a lubricant for a formulation many factors including
chemical instability, physical incompatibility, and lubrication efficiency should be considered.
Acknowledgments
The authors would like to thank Jennifer Wang of Teva Pharmaceutical Industries Limited
for suggestions.
Conflicts of Interest
The authors declare no conflict of interest.
References
1. Bowden, F.P.; Tabor, D. The Friction and Lubrication of Solids; Clarendon Press: Oxford, UK, 2001.
2. Wang, J.; Wen, H.; Desai, D. Lubrication in tablet formulations. Eur. J. Pharm. Biopharm. 2010,
75, 1–15.
3. Bolhuis, G.K.; Hölzer, A.W. Lubricant Sensitivity. In Pharmaceutical Powder Compaction
Technology, 1st ed.; Alderborn, G., Nyström, C., Eds.; Marcel Dekker, Inc.: New York, NY, USA,
1996; pp. 517–560.
4. Goldberg, R.; Klein, J. Liposomes as lubricants: Beyond drug delivery. Chem. Phys. Lipids 2012,
165, 374–381.
5. Faghihnejad, A.; Zeng, H. Fundamentals of Surface Adhesion, Friction, and Lubrication. In
Polymer Adhesion, Friction, and Lubrication; Zheng, H., Ed.; Wiley & Sons, Inc.: Hoboken, NJ,
USA, 2013; pp. 1–57.
6. Israelachvili, J.N. Intermolecular and Surface Forces, 3rd ed.; Elsevier: Burlington, MA, USA,
2011; pp. 469–499.
7. Pietsch, W. Size Enlargement by Agglomeration. In Handbook of Powder Science & Technology,
2nd ed.; Fayed, M.E., Otten, L., Eds.; Chapman & Hall: New York, NY, USA, 1997; pp. 202–295.
8. Butt, H.J.; Graf, K.; Kappl, M. Physics and Chemistry of Interfaces; Wiley-VCH: Weinheim,
Germany, 2003.
9. Bowden, F.P.; Tabor, D. Friction: An Introduction to Tribology; Doubleday & Company, Inc.:
Garden City, NY, USA, 1973.
10. Schulze, D. Powder and Bulk Solids: Behavior, Characterization, Storage and Flow;
Springer-Verlag: Heidelberg, Germany, 2008.
21. Lubricants 2014, 2 41
11. Gethin, D.T.; Solimanjad, N.; Doremus, P.; Korachkin, D. Friction and Its Measurement in
Powder-Compaction Processes. In Modelling of Powder Die Compaction; Brewin, P.R., Coube, O.,
Doremus, P., Tweed, J.H., Eds.; Springer-Verlag: London, UK, 2008; pp. 105–129.
12. Zimmermann, I.; Eber, M.; Meyer, K. Nanomaterials as flow regulators in dry powders.
Z. Phys. Chem. 2004, 218, 52–102.
13. Miller, T.A.; York, P. Pharmaceutical tablet lubrication. Int. J. Pharm. 1988, 41, 1–19.
14. O’Rourke, S.E.; Morris, R.H. Metallic stearate: A review of their function and use as release agents
for rubber compounds. Prog. Rubber Plast. Technol. 1998, 14, 238–247.
15. Abramovici, B.; Gromenil, J.C.; Molard, F.; Blanc, F. Comparative study on the lubricating
properties of a new additive: The glycerol tribehenate (Compritol®
888) compared to magnesium
stearate. Bull. Tech. Gattefosse 1985, 78, 75–85.
16. Aoshima, H.; Miyagisnima, A.; Nozawa, Y.; Sadzuka, Y.; Sonobe, T. Glycerin fatty acid esters as a
new lubricant of tablets. Int. J. Pharm. 2005, 293, 25–34.
17. Jannin, V.; Bérard, V.; N’Diaye, A.; Andrés, C.; Pourcelot, Y. Comparative study of the lubricant
performance of Compritol®
888 ATO either used by blending or by hot melt coating. Int. J. Pharm.
2003, 262, 39–45.
18. Dawoodbhai, S.S.; Chueh, H.R.; Rhodes, C.T. Glidants and lubricant properties of several types of
talcs. Drug Dev. Ind. Pharm. 1987, 13, 2441–2467.
19. Lapeyre, F.; Cuiné, A.; Chulia, D.; Vérain, A. Quantitative evaluation of tablet sticking
anti-adherent properties of some tablet lubricants. STP Pharma 1988, 4, 106–110.
20. Okoye, P.; Wu, S.H.; Dave, R.H. To evaluate the effect of various magnesium stearate polymorphs
using powder rheology and thermal analysis. Drug Dev. Ind. Pharm. 2012, 38, 1470–1478.
21. Bracconi, P.; Andrés, C.; Ndiaye, A. Structural properties of magnesium stearate pseudo-polymorphs:
Effect of temperature. Int. J. Pharm. 2003, 262, 109–124.
22. Rao, K.P.; Chawla, G.; Kaushal, A.M.; Bansal, A.K. Impact of solid-state properties on lubricant
efficacy of magnesium stearate. Pharm. Dev. Technol. 2005, 10, 423–437.
23. Ertel, K.D.; Carstensen, J.T. Chemical, physical, and lubricant properties of magnesium stearate.
J. Pharm. Sci. 1988, 77, 625–629.
24. Barra, J.; Somma, R. Influence of the physicochemical variability of magnesium stearate on its
lubricant properties: Possible solutions. Drug Dev. Ind. Pharm. 1996, 22, 1105–1120.
25. Dansereau, R.; Peck, G.E. The effect of the variability in the physical and chemical properties of
magnesium stearate on the properties of compressed tablets. Drug Dev. Ind. Pharm. 1987, 13,
975–999.
26. Soebagyo, S.S. The effect of the particle size of magnesium stearate on the dissolution of
dexamethasone from interactive mix tablet. Maj. Farm. Indones. 1994, 5, 52–58.
27. Kushner, J.I.V.; Langdon, B.A.; Hiller, J.I.; Carlson, G.T. Examining the impact of excipient
material property variation on drug product quality attributes: A quality-by-design study for a roller
compacted, immediate release tablet. J. Pharm. Sci. 2011, 100, 2222–2239.
28. Morin, G.; Briens, L. The effect of lubricants on powder flowability for pharmaceutical application.
AAPS PharmSciTech 2013, 14, 1158–1168.
22. Lubricants 2014, 2 42
29. Faqih, A.M.N.; Mehrotra, A.; Hammond, S.V.; Muzzio, F.J. Effect of moisture and magnesium
stearate concentration on flow properties of cohesive granular materials. Int. J. Pharm. 2007, 336,
338–345.
30. Liu, L.X.; Marziano, I.; Bentham, A.C.; Lister, J.D.; White, E.T.; Howes, T. Effect of particle
propertie on the flowability of ibuprofen powders. Int. J. Pharm. 2008, 362, 109–117.
31. Kikuta, J.; Kitamori, N. Effect of mixing time on the lubricating properties of magnesium stearate
and the final characteristics of the compressed tablets. Drug Dev. Ind. Pharm. 1994, 20, 343–355.
32. Perrault, M.; Bertrand, F.; Chaouki, J. An investigation of magnesium stearate mixing in a
V-blender through gamma-ray detection. Powder Technol. 2010, 200, 234–245.
33. He, X.R.; Secreast, P.J.; Amidon, G.E. Mechanistic study of the effect of roller compaction and
lubrication on tablet mechanical strength. J. Pharm. Sci. 2007, 96, 1342–1355.
34. Yu, S.; Adams, M.; Gururajan, B.; Reynolds, G.; Roberts, R.; Wu, C.Y. The effect of lubrication on
roll compaction, ribbon milling, and tableting. Chem. Eng. Sci. 2013, 86, 9–18.
35. Miguélez-Morán, A.M.; Wu, C.Y.; Seville, J.P.K. The effect of lubrication on density distribution
of roller compacted ribbons. Int. J. Pharm. 2008, 362, 52–59.
36. Terashita, K. Meeting PAT requirement by evaluating the mixing and distribution of magnesium
stearate lubricant and other components in a tablet Blend using on-line analytical method part 2.
Pharm. Technol. Jpn. 2012, 28, 1275–1278.
37. Šašiċ, S.; Ojakovo, P.; Warman, M.; Sanghvi, T. Raman chemical mapping of magnesium stearate
delivered by a punch-face lubrication system on the surface of placebo and active tablets.
Appl. Spectrosc. 2013, 67, 1073–1079.
38. Yoshihashi, Y.; Sato, M.; Kawano, Y.; Yonemochi, E.; Terada, K. Evaluation of physicochemical
properties on the blending process of pharmaceutical granules with magnesium stearate by thermal
effusivity sensor. J. Therm. Anal. Calorim. 2013, 113, 1281–1285.
39. Kararli, T.T.; Needham, T.E.; Seul, C.J.; Finnegan, P.M. Solid state interaction of magnesium oxide
and ibuprofen to form a salt. Pharm. Res. 1989, 6, 804–808.
40. Botha, S.A.; Lötter, A.P. Compatibility study between naproxen and tablet excipients using
differential scanning calorimetry. Drug Dev. Ind. Pharm. 1990, 16, 673–683.
41. Mura, P.; Manderioli, A.; Bramanti, G.; Furlanetto, S.; Pinzauti, S. Utilization of differential
scanning calorimetry as a screening technique to determine the compatibility of ketoprofen with
excipients. Int. J. Pharm. 1995, 119, 71–79.
42. Marcotegui, F.; Sanchez Monge, J.M. Application of differential thermal analysis to study the
stability of acetylsalicylic acid in the solid state. I. Hydrolysis of acetylsalicylic acid. Revist. Asoc.
Esp. Farm. Hosp. 1981, 5, 5–10.
43. Ahlneck, C.; Waltersson, J.O.; Lundgren, P. Difference in effect of powdered and granular
magnesium stearate on the solid state stability of acetylsalicylic acid. Acta Pharm. Technol. 1987,
33, 21–26.
44. Fouda, M.A.; Mady, O.Y.; El-Azab, G.A. Stabilization and control of aspirin release via solid
dispersion systems. Mansoura J. Pharm. Sci. 1998, 14, 36–70.
45. Kornblum, S.S.; Zoglio, M.A. Pharmaceutical heterogeneous systems I. Hydrolysis of aspirin in
combination with tablet lubricants in an aqueous suspension. J. Pharm. Sci. 1967, 56, 1569–1575.