The document is an international patent application for pharmaceutical compositions of ibuprofen or its pharmaceutically acceptable salts. It summarizes various challenges with producing stable ibuprofen formulations, such as poor compressibility and adhesion during processing. The invention claims to provide a cost-effective method of producing ibuprofen granules with good flow properties and minimal weight variation through the use of glidants in three stages of formulation. It seeks patent protection for pharmaceutical compositions of ibuprofen and the process for their production.
This document describes a process for producing sulphinyl ethyl thiophosphates. It involves reacting a salt of a compound of the formula (RO)(R'O)P(O)SH with a compound of the formula XC2H4S(O)R", where R and R" are alkyl groups with 4 or fewer carbon atoms and X is a halogen atom. The reaction can use solvents like alcohols or ketones and produces the desired sulphinyl ethyl thiophosphate compounds in good yield. An example reaction uses a salt of the formula (RO)(R'O)P(O)SM, where M is an alkali metal, with eth
This patent application describes dispersible concentrate (DC) compositions containing metconazole, non-ionic surfactants, and solvents. The compositions form nano-suspensions of metconazole particles less than 30 nm when diluted with water. The compositions provide improved dispersion properties and biological efficacy compared to other metconazole formulations. Methods of preparing nano-suspensions and ready-to-use products from the DC compositions are also disclosed for treating plants to protect against fungi.
Physicochemical Characteristics of Fumarized and Maleinized Cottonseed Oiltheijes
The International Journal of Engineering & Science is aimed at providing a platform for researchers, engineers, scientists, or educators to publish their original research results, to exchange new ideas, to disseminate information in innovative designs, engineering experiences and technological skills. It is also the Journal's objective to promote engineering and technology education. All papers submitted to the Journal will be blind peer-reviewed. Only original articles will be published.
The papers for publication in The International Journal of Engineering& Science are selected through rigorous peer reviews to ensure originality, timeliness, relevance, and readability.
Theoretical work submitted to the Journal should be original in its motivation or modeling structure. Empirical analysis should be based on a theoretical framework and should be capable of replication. It is expected that all materials required for replication (including computer programs and data sets) should be available upon request to the authors.
The International Journal of Engineering & Science would take much care in making your article published without much delay with your kind cooperation
The patent describes a process for producing solid granules containing aromatic substances. The process involves coating a core, made of excipients with or without active substances, in three steps to form concentric layers. Each layer is formed by coating the core with active substances combined with excipients, drying the layer, and screening the coated core. The granules can be chewed, sucked, swallowed or dissolved and are used to deliver plant extracts, essential oils, and other active ingredients.
Biomass Refinery – a way to Produce Value Added Products from Agricultural Bi...IJMERJOURNAL
ABSTRACT: Production of furfural from pentosan in sunflower husk was carried out in an attempt to produce value-added products from sunflower husk which is commonly burnt around sunflower oil mills of India. This process involved the conversion of sunflower husk into xylose, which was then cyclodehydrated to furfural using dilute sulphuric acid. Product was characterized by volumetric process such as bromine- bromide excess method. Furfural obtained was analyzed using gas chromatography (GC) and gas chromatography with mass spectrophotometer (GC-MS). The product was colourless, but turned yellowish and then dark brown upon exposure to air and light. Furfural obtained was in liquid form, with a molecular weight of 96.2 g/mole and the formula of C5H4O2
integrated sophorolipid production and gravity separationBen Dolman
The document describes an integrated method for separating sophorolipid glycolipid biosurfactants from fermentation broth using gravity separation. A novel settling column was developed and demonstrated to continuously remove and recover an enriched sophorolipid phase from the fermenter, while recirculating cells and media back to the bioreactor. This integrated separation approach allowed for an 11% reduction in fermenter volume needed, sophorolipid recoveries up to 86%, and a 34% reduction in mixing power requirements. It also enabled extending the fermentation duration to over 1000 hours and producing over 600g of sophorolipid from an initial 1L batch volume.
Mechanism of aerobic & an aerobic biodegradation07sudha
The document discusses the mechanisms of aerobic and anaerobic biodegradation. It explains that aerobic biodegradation breaks down organic contaminants using oxygen, while anaerobic biodegradation occurs without oxygen. The key stages of anaerobic biodegradation are hydrolysis, acidogenesis, acetogenesis, and methanogenesis. It also compares aerobic and anaerobic biodegradation, noting that aerobic is faster but anaerobic produces less waste. Various microorganisms involved in each process are also identified.
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 describes a process for producing sulphinyl ethyl thiophosphates. It involves reacting a salt of a compound of the formula (RO)(R'O)P(O)SH with a compound of the formula XC2H4S(O)R", where R and R" are alkyl groups with 4 or fewer carbon atoms and X is a halogen atom. The reaction can use solvents like alcohols or ketones and produces the desired sulphinyl ethyl thiophosphate compounds in good yield. An example reaction uses a salt of the formula (RO)(R'O)P(O)SM, where M is an alkali metal, with eth
This patent application describes dispersible concentrate (DC) compositions containing metconazole, non-ionic surfactants, and solvents. The compositions form nano-suspensions of metconazole particles less than 30 nm when diluted with water. The compositions provide improved dispersion properties and biological efficacy compared to other metconazole formulations. Methods of preparing nano-suspensions and ready-to-use products from the DC compositions are also disclosed for treating plants to protect against fungi.
Physicochemical Characteristics of Fumarized and Maleinized Cottonseed Oiltheijes
The International Journal of Engineering & Science is aimed at providing a platform for researchers, engineers, scientists, or educators to publish their original research results, to exchange new ideas, to disseminate information in innovative designs, engineering experiences and technological skills. It is also the Journal's objective to promote engineering and technology education. All papers submitted to the Journal will be blind peer-reviewed. Only original articles will be published.
The papers for publication in The International Journal of Engineering& Science are selected through rigorous peer reviews to ensure originality, timeliness, relevance, and readability.
Theoretical work submitted to the Journal should be original in its motivation or modeling structure. Empirical analysis should be based on a theoretical framework and should be capable of replication. It is expected that all materials required for replication (including computer programs and data sets) should be available upon request to the authors.
The International Journal of Engineering & Science would take much care in making your article published without much delay with your kind cooperation
The patent describes a process for producing solid granules containing aromatic substances. The process involves coating a core, made of excipients with or without active substances, in three steps to form concentric layers. Each layer is formed by coating the core with active substances combined with excipients, drying the layer, and screening the coated core. The granules can be chewed, sucked, swallowed or dissolved and are used to deliver plant extracts, essential oils, and other active ingredients.
Biomass Refinery – a way to Produce Value Added Products from Agricultural Bi...IJMERJOURNAL
ABSTRACT: Production of furfural from pentosan in sunflower husk was carried out in an attempt to produce value-added products from sunflower husk which is commonly burnt around sunflower oil mills of India. This process involved the conversion of sunflower husk into xylose, which was then cyclodehydrated to furfural using dilute sulphuric acid. Product was characterized by volumetric process such as bromine- bromide excess method. Furfural obtained was analyzed using gas chromatography (GC) and gas chromatography with mass spectrophotometer (GC-MS). The product was colourless, but turned yellowish and then dark brown upon exposure to air and light. Furfural obtained was in liquid form, with a molecular weight of 96.2 g/mole and the formula of C5H4O2
integrated sophorolipid production and gravity separationBen Dolman
The document describes an integrated method for separating sophorolipid glycolipid biosurfactants from fermentation broth using gravity separation. A novel settling column was developed and demonstrated to continuously remove and recover an enriched sophorolipid phase from the fermenter, while recirculating cells and media back to the bioreactor. This integrated separation approach allowed for an 11% reduction in fermenter volume needed, sophorolipid recoveries up to 86%, and a 34% reduction in mixing power requirements. It also enabled extending the fermentation duration to over 1000 hours and producing over 600g of sophorolipid from an initial 1L batch volume.
Mechanism of aerobic & an aerobic biodegradation07sudha
The document discusses the mechanisms of aerobic and anaerobic biodegradation. It explains that aerobic biodegradation breaks down organic contaminants using oxygen, while anaerobic biodegradation occurs without oxygen. The key stages of anaerobic biodegradation are hydrolysis, acidogenesis, acetogenesis, and methanogenesis. It also compares aerobic and anaerobic biodegradation, noting that aerobic is faster but anaerobic produces less waste. Various microorganisms involved in each process are also identified.
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 .
Mixotrophic Cultivation of Botryococcus Braunii for Biomass and Lipid Yields ...IJERA Editor
In the present study an attempt has been made to utilize glucose as a carbon source to cultivate Botyrococcusbrauniimixotrophically with CO2 inputs to achieve biomass and lipid yields along with CO2 reduction. Experiments were carried out in laboratory culture flasks using different glucose concentrations (1g/L, 1.5g/L, 2g/L, 2.5g/L, 3g/L, 3.5g/L, 4g/L, 4.5g/L and 5g/L) with 6% CO2 inputs at a flow rate of 0.1vvm at different time intervals of CO2 aeration (1hr/d, 2hr/d, 4hr/d, 6hr/d, 8hr/d, 10h/d, 12h/d and 24hr/d). The maximum biomass and lipid yields of 2.43g/L and 1.29g/L respectively were obtained at the glucose concentration of 2.5g/L. On the other hand the CO2 removal efficiency reached upto 75%. Hence in the present study it was observed that the microalgaeB. bauniigrew efficiently in the mixotrophic cultivation mode utilizing the glucose and CO2 as carbon source for its growth to achieve CO2reduction and in turn it produced biomass and lipids yields efficiently.
Biosynthesis of Polyhydroxyalkanoate blends from Cassia Seed: GalactoMannan a...IRJET Journal
This document summarizes research on producing polyhydroxybutyrate (PHB) blends and copolymers from cassia seeds for use as biodegradable plastics. Key points:
- PHB was produced from Bacillus safensis EBT1 and blended with galactomannan (GM) extracted from cassia seeds to improve flexibility. Different blend ratios were tested.
- Copolymers of PHB and GM (PHB-co-GM) were also produced using various carbon source ratios to obtain optimal yield.
- Blend and copolymer films were evaluated for properties like thickness, strength and water absorption. PHB-co-GM films showed better visual
This patent application is for a physiological saline solution containing graphene. It describes dispersing graphene powder less than 1nm in size into saline solutions, Ringers solution, or dextrose in water. The graphene-containing solutions can be used to treat diseases like dementia, Parkinson's, and viruses. The graphene adheres to virus particles and prevents them from acting on the human body. Surfactants or other additives may be included to improve graphene dispersion and prevent particle coagulation over time. Priority is claimed for earlier Korean patent applications.
7 soybean curd residue composition and utilizationgiangcoi2195
This document reviews the composition, utilization, and limiting factors of soybean curd residue (SCR). SCR is a byproduct of tofu and soymilk production that is rich in various nutrients like protein, fiber, vitamins, minerals, and bioactive compounds. However, SCR is often considered waste due to its high moisture content and bulk. The document finds that SCR has potential value as a food ingredient if its limitations are addressed. SCR contains various nutrients and compounds that can provide health benefits. However, further research is still needed to optimize processing methods to improve properties like protein solubility and develop more applications for commercial utilization of SCR.
Synthesis of bioethanol from tamarind seeds using marine strain of Saccharomy...Asheesh Padiyar
Bioethanol can be used as a second generation advanced biofuels. Currently it is mainly produced from starch but bioethanol production from starch leads to competition for food, land and price. Therefore, ligno-cellulosic agricultural residues are potentially used for bioethanol production to solve such challenges. In the present work acid pretreated tamarind kernel powder is used as a ligno-cellulosic biomass for bioethanol production using marine yeast. Greater osmosis tolerance, greater special chemical productivity and production of industrial enzymes are the unique characteristics of marine yeast over terrestrial strains. Hence, marine yeasts have great
potential to be applied in various industries. Therefore, the marine strain of saccharomyces cerevisiaewas isolated from marine water and was used for bioethanol production and the bioethanol yield was optimized using the full factorial design methodology. The amount of Bioethanol yield on day 2 was found to be 2.3g/l and the interaction effects were also studied using Minitab 17 software.
This document discusses methods for recovering solvent mixtures using sodium chloride as an additive. It presents the results of experiments conducted using a rotary evaporator to recover solvents from mixtures as condensate. Adding sodium chloride to the crude mixtures improved the amount of recovered solvent by up to 20% compared to mixtures without sodium chloride. Higher recovery was achieved at higher bath temperatures and evaporator rotation speeds. The addition of sodium chloride reduces the boiling point of mixtures and allows for more efficient solvent recovery that saves energy compared to conventional distillation methods.
This document describes research into developing a new formulation map for high-shear wet granulation processes using on-line torque measurements. The researchers conducted experiments varying formulation parameters like binder type and amount, as well as diluent particle size, to determine the minimum liquid volume needed for granule growth. They found that granulation onset, identified by an abrupt increase in torque, requires the liquid added to exceed a minimum threshold volume. This minimum liquid volume depends on factors like the dry binder type, amount, and diluent properties. They also showed this formulation map could be constructed using independent measurements of binder glass transition temperatures under different humidity conditions.
Formulation and in vitro study of ibuprofen loaded crosslinked sodium alginat...Shouvik Mondal
Ibuprofen loaded microspheres were prepared using sodium alginate and gellan gum and were cross-linked by maleic anhydride, aluminium chloride. The resulting microspheres were evaluated by in-vitro release study, swelling index, microscopic analysis and entrapment efficiency. DSC study shows there was no interaction between drug and excipients.
Entrapment was found good in all the formulations while the maximum entrapment (97.6%) was recorded in formulation
cross-linked by aluminium chloride and their average particle size were 150 to 160 µm. Approximately 50% of drug was
released by the formulation cross-linked by aluminium chloride (F2) over a period of 6 hours. From this experiment, it is observed that the formulation with cross-linked by aluminium chloride is the better formulation among others due to good release profile and entrapment efficiency.
The document summarizes the development of an extended release formulation of bupropion hydrochloride tablets. The objectives were to develop a stable, cost-effective ER formulation and compare it to marketed products. Various ER tablet formulations were prepared using different concentrations of coating polymers and evaluated for drug release. Formulations F9 and F10, which used 8% coating of ethylcellulose 15cps, showed comparable release to the reference product over 16 hours. The developed formulation met the objectives of providing a once-daily ER tablet for bupropion hydrochloride.
This patent relates to polysulfone compositions made from aromatic dihydroxy monomers that do not exhibit estradiol binding activity. The polysulfones and their residual monomers or degradation products similarly exhibit little to no estradiol binding activity. The patent discloses polysulfone compositions, polymer blends containing polysulfones, methods for manufacturing polysulfones from monomers with low estradiol binding activity, and articles made from such polysulfones.
Fruit Seeds as Potential Coagulants in Water PurgationIRJET Journal
This study evaluated the effectiveness of natural coagulants from fruit seeds to reduce turbidity in water samples. Papaya, watermelon, jackfruit, and pumpkin seed powders were tested at different dosages using a jar test apparatus. Papaya seed powder achieved the highest turbidity removal rate of 88% at a dosage of 0.8g/l, reducing turbidity from 25 NTU to 3 NTU. Watermelon seed powder achieved 84.8% removal at 0.6g/l, jackfruit was 76% at 0.6g/l, and pumpkin was 80% at 0.6g/l. Papaya seed powder was the most effective natural coagulant for turbidity reduction according
Isolation and Screening of Hydrogen Producing Bacterial Strain from Sugarcane...Editor IJCATR
The aim of this study is to isolate a highly competent bacterium with potent cellulose degrading capability and a better
hydrogen producer. Soil sample from sugarcane bagasse yard was isolated, serially diluted and plated on cellulose specific nutrient
agar plate. Four colonies have been isolated in which a single colony has potent cellulose degrading ability and the highest hydrogen
productivity of 275.13 mL H2 L-1. The newly isolated bacterium was morphologically and biochemically characterized. The
molecular characterization of the bacterium was carried out using 16S rDNA sequencing and the organism was identified as
Bacilllus subtilis AuChE413. Proteomic analysis such as MALDI-TOF was carried out to differentiate the isolated Bacillus subtilis
from Bacillus thuringiensis and Bacillus amyloliquefaciens. Phylogenetic tree was constructed to analyze the evolutionary
relationship among different genus and species with the newly isolated strain.
This document describes the preparation of bismuth oxide (Bi2O3) via a simple and energy efficient solution combustion synthesis method using sucrose as a fuel. The synthesized SCS-Bi2O3 is characterized and found to have high surface area and porosity. This SCS-Bi2O3 is then used as an effective base-catalyst for Suzuki-coupling reactions of various halopyridines and boronic acids in aqueous medium. Some of the coupled heterocyclic compounds show anti-cancer activity against human hepatoma cancer cells. The SCS-Bi2O3 catalyst can be recycled and reused at least three times without significant loss of activity.
This document describes a method of applying a protective resinous coating to heat-sensitive electrical elements by polymerizing polymerizable organic compounds using high energy electrons or cathode rays. Specifically, it involves surrounding the electrical element with a monomeric compound and irradiating it with high energy electrons to polymerize the monomer into a solid polymer coating without damaging the heat-sensitive component inside. This allows for rapid encapsulation of elements like resistors, capacitors, transistors, and diodes without impairing their properties through the application of heat.
IRJET - Formulation and Evaluation of Tinidazole Loaded Fast Dissolving TabletsIRJET Journal
1) The document describes the formulation and evaluation of fast dissolving tablets containing the drug tinidazole. Six tablet formulations (T1-T6) were prepared using different ratios of natural and synthetic polymers as excipients.
2) The formulations were evaluated for hardness, friability, weight variation, drug content uniformity, disintegration time, and in-vitro drug release. Formulation T5 had the fastest disintegration time of under 1 minute and drug release of 80% within 6 minutes.
3) The study demonstrated that the selected polymer blends could be used to effectively formulate fast dissolving tablets of tinidazole with rapid disintegration and dissolution properties suitable for patients with swallowing difficulties
This document discusses nano spray drying technology for food ingredients. Conventional spray drying produces microparticle powders, while nano spray drying can produce nanoparticles from 300 nm to 5 μm using ultrasonic atomization and an electrostatic collector. Key advantages of nano spray drying include improved bioavailability, controlled release, and stability of encapsulated food ingredients. The document outlines the process of nano spray drying and provides examples of food ingredients that have been nanoencapsulated. Challenges with scaling up the technology are also discussed.
Formulation Development and Evaluation of Tablet Formulation Containing Ibupr...ijtsrd
The purpose of this study was to formulate and evaluate conventional tablets of Ibuprofen HCl with Castor oil. Castor oil helps to overcome the hepatotoxic effect of Ibuprofen HCl. Direct compression method was used to formulate tablets, which contained Castor oil in different proportion from batch F1 F4. Formulation of tablets was prepared by the powder blend of different ratios of Castor oil to get desirable drug release profile. All batches were evaluated for flow property Pre compression study . Evaluation parameters of formulated tablets were hardness, friability, thickness, drug content, weight variation, and the in vitro drug release rate pattern. Results indicated that the formulation F2 was the most promising formulation as the drug release from this formulation was high as compared to other formulations. In formulation F2, percentage drug release of Ibuprofen HCl is 97.01 at 60 min. Gayatri Burte | Vikram Veer | Ashok Bhosale "Formulation Development and Evaluation of Tablet Formulation Containing Ibuprofen HCL with Castor Oil" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-4 , June 2022, URL: https://www.ijtsrd.com/papers/ijtsrd50389.pdf Paper URL: https://www.ijtsrd.com/pharmacy/other/50389/formulation-development-and-evaluation-of-tablet-formulation-containing-ibuprofen-hcl-with-castor-oil/gayatri-burte
The invention provides a disposable stone paper foamed tableware produced with gypsum powder and a preparation method thereof. It is composed of the following components in parts by weight: 77 to 90% of gypsum powder, 7 to 13% of polypropylene, 0.5 to 1.5% of surface modifier, 0.5 to 2.5% of foaming agent, degradation Agent 0.5-1.5%, compatibilizer 0.5-1.5%, processing aid 1-3%. It is prepared through the steps of surface modification, mixing and molding of gypsum powder. The disposable stonepaper foamed tableware prepared by the invention has good water resistance, strong oil resistance, good thermal insulation effect, high strength, light specific gravity, good load-bearing ability, and can be environmentally degraded within 15 to 90 days. The product is degraded Later it can also be used as soil conditioner and fertilizer. It is the newest environmentally degradable stone paper packaging material.
Wurster Fluidised Bed Coating of Microparticles: Towards Scalable Production ...Valentyn Mohylyuk
Suspension of microparticles in an easy-to-swallow liquid is one approach to develop sustained-release formulations for children and patients with swallowing difficulties. However, to date production of sustained-release microparticles at the industrial scale has proven to be challenging. The aim of this investigation was to develop an innovative concept in coating sustained-release microparticles using industrial scalable Wurster fluidised bed to produce oral liquid suspensions. Microcrystalline cellulose cores (particle size <150 μm) were coated with Eudragit® NM 30 D and Eudragit® RS/RL 30 D aqueous dispersions using a fluidised bed coater. A novel approach of periodic addition of a small quantity (0.1% w/w) of dry powder glidant, magnesium stearate, to the coating chamber via an external port was applied throughout the coating process. This method significantly increased coating production yield from less than 50% to up to 99% compared to conventional coating
process without the dry powder glidant. Powder rheology tests showed that dry powder glidants increased the tapped density and decreased the cohesive index of coated microparticles. Reproducible microencapsulation of a highly water-soluble drug, metoprolol succinate, was achieved, yielding coated microparticles less than 200 μm in size with 20-h sustained drug release, suitable for use in liquid suspensions. The robust, scalable technology presented in this study offers an important solution to the long-standing challenges of formulating sustained-release dosage forms suitable for children and older people with swallowing difficulties.
Basic Candlestick Pattern in stock market, financeGuru Balaji .S
The document provides information on various candlestick patterns used in technical analysis of financial markets. It begins with definitions of basic candlestick types like doji and hanging man candles. It then outlines several reversal patterns like morning star and engulfing patterns that indicate a change in trend. Continuation patterns like rising three methods and falling three methods that suggest the current trend will persist are also discussed. The document provides illustrations and explanations of many common candlestick patterns to help readers understand how to interpret these visual representations of market price action.
This document outlines various types and uses of purified water in pharmaceutical applications. It discusses drinking water that meets EPA or international standards which can be used directly if compatible. It then lists several typical water treatment steps like deionization, reverse osmosis, and distillation used to produce purified water for special pharmaceutical purposes like API processes. The document categorizes purified water products for uses such as hemodialysis, analytical reagents, cleaning/ingredients for non-parenteral dosage forms, and various sterile purified waters for injection, irrigation, inhalation after additional packaging and sterilization steps.
Mixotrophic Cultivation of Botryococcus Braunii for Biomass and Lipid Yields ...IJERA Editor
In the present study an attempt has been made to utilize glucose as a carbon source to cultivate Botyrococcusbrauniimixotrophically with CO2 inputs to achieve biomass and lipid yields along with CO2 reduction. Experiments were carried out in laboratory culture flasks using different glucose concentrations (1g/L, 1.5g/L, 2g/L, 2.5g/L, 3g/L, 3.5g/L, 4g/L, 4.5g/L and 5g/L) with 6% CO2 inputs at a flow rate of 0.1vvm at different time intervals of CO2 aeration (1hr/d, 2hr/d, 4hr/d, 6hr/d, 8hr/d, 10h/d, 12h/d and 24hr/d). The maximum biomass and lipid yields of 2.43g/L and 1.29g/L respectively were obtained at the glucose concentration of 2.5g/L. On the other hand the CO2 removal efficiency reached upto 75%. Hence in the present study it was observed that the microalgaeB. bauniigrew efficiently in the mixotrophic cultivation mode utilizing the glucose and CO2 as carbon source for its growth to achieve CO2reduction and in turn it produced biomass and lipids yields efficiently.
Biosynthesis of Polyhydroxyalkanoate blends from Cassia Seed: GalactoMannan a...IRJET Journal
This document summarizes research on producing polyhydroxybutyrate (PHB) blends and copolymers from cassia seeds for use as biodegradable plastics. Key points:
- PHB was produced from Bacillus safensis EBT1 and blended with galactomannan (GM) extracted from cassia seeds to improve flexibility. Different blend ratios were tested.
- Copolymers of PHB and GM (PHB-co-GM) were also produced using various carbon source ratios to obtain optimal yield.
- Blend and copolymer films were evaluated for properties like thickness, strength and water absorption. PHB-co-GM films showed better visual
This patent application is for a physiological saline solution containing graphene. It describes dispersing graphene powder less than 1nm in size into saline solutions, Ringers solution, or dextrose in water. The graphene-containing solutions can be used to treat diseases like dementia, Parkinson's, and viruses. The graphene adheres to virus particles and prevents them from acting on the human body. Surfactants or other additives may be included to improve graphene dispersion and prevent particle coagulation over time. Priority is claimed for earlier Korean patent applications.
7 soybean curd residue composition and utilizationgiangcoi2195
This document reviews the composition, utilization, and limiting factors of soybean curd residue (SCR). SCR is a byproduct of tofu and soymilk production that is rich in various nutrients like protein, fiber, vitamins, minerals, and bioactive compounds. However, SCR is often considered waste due to its high moisture content and bulk. The document finds that SCR has potential value as a food ingredient if its limitations are addressed. SCR contains various nutrients and compounds that can provide health benefits. However, further research is still needed to optimize processing methods to improve properties like protein solubility and develop more applications for commercial utilization of SCR.
Synthesis of bioethanol from tamarind seeds using marine strain of Saccharomy...Asheesh Padiyar
Bioethanol can be used as a second generation advanced biofuels. Currently it is mainly produced from starch but bioethanol production from starch leads to competition for food, land and price. Therefore, ligno-cellulosic agricultural residues are potentially used for bioethanol production to solve such challenges. In the present work acid pretreated tamarind kernel powder is used as a ligno-cellulosic biomass for bioethanol production using marine yeast. Greater osmosis tolerance, greater special chemical productivity and production of industrial enzymes are the unique characteristics of marine yeast over terrestrial strains. Hence, marine yeasts have great
potential to be applied in various industries. Therefore, the marine strain of saccharomyces cerevisiaewas isolated from marine water and was used for bioethanol production and the bioethanol yield was optimized using the full factorial design methodology. The amount of Bioethanol yield on day 2 was found to be 2.3g/l and the interaction effects were also studied using Minitab 17 software.
This document discusses methods for recovering solvent mixtures using sodium chloride as an additive. It presents the results of experiments conducted using a rotary evaporator to recover solvents from mixtures as condensate. Adding sodium chloride to the crude mixtures improved the amount of recovered solvent by up to 20% compared to mixtures without sodium chloride. Higher recovery was achieved at higher bath temperatures and evaporator rotation speeds. The addition of sodium chloride reduces the boiling point of mixtures and allows for more efficient solvent recovery that saves energy compared to conventional distillation methods.
This document describes research into developing a new formulation map for high-shear wet granulation processes using on-line torque measurements. The researchers conducted experiments varying formulation parameters like binder type and amount, as well as diluent particle size, to determine the minimum liquid volume needed for granule growth. They found that granulation onset, identified by an abrupt increase in torque, requires the liquid added to exceed a minimum threshold volume. This minimum liquid volume depends on factors like the dry binder type, amount, and diluent properties. They also showed this formulation map could be constructed using independent measurements of binder glass transition temperatures under different humidity conditions.
Formulation and in vitro study of ibuprofen loaded crosslinked sodium alginat...Shouvik Mondal
Ibuprofen loaded microspheres were prepared using sodium alginate and gellan gum and were cross-linked by maleic anhydride, aluminium chloride. The resulting microspheres were evaluated by in-vitro release study, swelling index, microscopic analysis and entrapment efficiency. DSC study shows there was no interaction between drug and excipients.
Entrapment was found good in all the formulations while the maximum entrapment (97.6%) was recorded in formulation
cross-linked by aluminium chloride and their average particle size were 150 to 160 µm. Approximately 50% of drug was
released by the formulation cross-linked by aluminium chloride (F2) over a period of 6 hours. From this experiment, it is observed that the formulation with cross-linked by aluminium chloride is the better formulation among others due to good release profile and entrapment efficiency.
The document summarizes the development of an extended release formulation of bupropion hydrochloride tablets. The objectives were to develop a stable, cost-effective ER formulation and compare it to marketed products. Various ER tablet formulations were prepared using different concentrations of coating polymers and evaluated for drug release. Formulations F9 and F10, which used 8% coating of ethylcellulose 15cps, showed comparable release to the reference product over 16 hours. The developed formulation met the objectives of providing a once-daily ER tablet for bupropion hydrochloride.
This patent relates to polysulfone compositions made from aromatic dihydroxy monomers that do not exhibit estradiol binding activity. The polysulfones and their residual monomers or degradation products similarly exhibit little to no estradiol binding activity. The patent discloses polysulfone compositions, polymer blends containing polysulfones, methods for manufacturing polysulfones from monomers with low estradiol binding activity, and articles made from such polysulfones.
Fruit Seeds as Potential Coagulants in Water PurgationIRJET Journal
This study evaluated the effectiveness of natural coagulants from fruit seeds to reduce turbidity in water samples. Papaya, watermelon, jackfruit, and pumpkin seed powders were tested at different dosages using a jar test apparatus. Papaya seed powder achieved the highest turbidity removal rate of 88% at a dosage of 0.8g/l, reducing turbidity from 25 NTU to 3 NTU. Watermelon seed powder achieved 84.8% removal at 0.6g/l, jackfruit was 76% at 0.6g/l, and pumpkin was 80% at 0.6g/l. Papaya seed powder was the most effective natural coagulant for turbidity reduction according
Isolation and Screening of Hydrogen Producing Bacterial Strain from Sugarcane...Editor IJCATR
The aim of this study is to isolate a highly competent bacterium with potent cellulose degrading capability and a better
hydrogen producer. Soil sample from sugarcane bagasse yard was isolated, serially diluted and plated on cellulose specific nutrient
agar plate. Four colonies have been isolated in which a single colony has potent cellulose degrading ability and the highest hydrogen
productivity of 275.13 mL H2 L-1. The newly isolated bacterium was morphologically and biochemically characterized. The
molecular characterization of the bacterium was carried out using 16S rDNA sequencing and the organism was identified as
Bacilllus subtilis AuChE413. Proteomic analysis such as MALDI-TOF was carried out to differentiate the isolated Bacillus subtilis
from Bacillus thuringiensis and Bacillus amyloliquefaciens. Phylogenetic tree was constructed to analyze the evolutionary
relationship among different genus and species with the newly isolated strain.
This document describes the preparation of bismuth oxide (Bi2O3) via a simple and energy efficient solution combustion synthesis method using sucrose as a fuel. The synthesized SCS-Bi2O3 is characterized and found to have high surface area and porosity. This SCS-Bi2O3 is then used as an effective base-catalyst for Suzuki-coupling reactions of various halopyridines and boronic acids in aqueous medium. Some of the coupled heterocyclic compounds show anti-cancer activity against human hepatoma cancer cells. The SCS-Bi2O3 catalyst can be recycled and reused at least three times without significant loss of activity.
This document describes a method of applying a protective resinous coating to heat-sensitive electrical elements by polymerizing polymerizable organic compounds using high energy electrons or cathode rays. Specifically, it involves surrounding the electrical element with a monomeric compound and irradiating it with high energy electrons to polymerize the monomer into a solid polymer coating without damaging the heat-sensitive component inside. This allows for rapid encapsulation of elements like resistors, capacitors, transistors, and diodes without impairing their properties through the application of heat.
IRJET - Formulation and Evaluation of Tinidazole Loaded Fast Dissolving TabletsIRJET Journal
1) The document describes the formulation and evaluation of fast dissolving tablets containing the drug tinidazole. Six tablet formulations (T1-T6) were prepared using different ratios of natural and synthetic polymers as excipients.
2) The formulations were evaluated for hardness, friability, weight variation, drug content uniformity, disintegration time, and in-vitro drug release. Formulation T5 had the fastest disintegration time of under 1 minute and drug release of 80% within 6 minutes.
3) The study demonstrated that the selected polymer blends could be used to effectively formulate fast dissolving tablets of tinidazole with rapid disintegration and dissolution properties suitable for patients with swallowing difficulties
This document discusses nano spray drying technology for food ingredients. Conventional spray drying produces microparticle powders, while nano spray drying can produce nanoparticles from 300 nm to 5 μm using ultrasonic atomization and an electrostatic collector. Key advantages of nano spray drying include improved bioavailability, controlled release, and stability of encapsulated food ingredients. The document outlines the process of nano spray drying and provides examples of food ingredients that have been nanoencapsulated. Challenges with scaling up the technology are also discussed.
Formulation Development and Evaluation of Tablet Formulation Containing Ibupr...ijtsrd
The purpose of this study was to formulate and evaluate conventional tablets of Ibuprofen HCl with Castor oil. Castor oil helps to overcome the hepatotoxic effect of Ibuprofen HCl. Direct compression method was used to formulate tablets, which contained Castor oil in different proportion from batch F1 F4. Formulation of tablets was prepared by the powder blend of different ratios of Castor oil to get desirable drug release profile. All batches were evaluated for flow property Pre compression study . Evaluation parameters of formulated tablets were hardness, friability, thickness, drug content, weight variation, and the in vitro drug release rate pattern. Results indicated that the formulation F2 was the most promising formulation as the drug release from this formulation was high as compared to other formulations. In formulation F2, percentage drug release of Ibuprofen HCl is 97.01 at 60 min. Gayatri Burte | Vikram Veer | Ashok Bhosale "Formulation Development and Evaluation of Tablet Formulation Containing Ibuprofen HCL with Castor Oil" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-4 , June 2022, URL: https://www.ijtsrd.com/papers/ijtsrd50389.pdf Paper URL: https://www.ijtsrd.com/pharmacy/other/50389/formulation-development-and-evaluation-of-tablet-formulation-containing-ibuprofen-hcl-with-castor-oil/gayatri-burte
The invention provides a disposable stone paper foamed tableware produced with gypsum powder and a preparation method thereof. It is composed of the following components in parts by weight: 77 to 90% of gypsum powder, 7 to 13% of polypropylene, 0.5 to 1.5% of surface modifier, 0.5 to 2.5% of foaming agent, degradation Agent 0.5-1.5%, compatibilizer 0.5-1.5%, processing aid 1-3%. It is prepared through the steps of surface modification, mixing and molding of gypsum powder. The disposable stonepaper foamed tableware prepared by the invention has good water resistance, strong oil resistance, good thermal insulation effect, high strength, light specific gravity, good load-bearing ability, and can be environmentally degraded within 15 to 90 days. The product is degraded Later it can also be used as soil conditioner and fertilizer. It is the newest environmentally degradable stone paper packaging material.
Wurster Fluidised Bed Coating of Microparticles: Towards Scalable Production ...Valentyn Mohylyuk
Suspension of microparticles in an easy-to-swallow liquid is one approach to develop sustained-release formulations for children and patients with swallowing difficulties. However, to date production of sustained-release microparticles at the industrial scale has proven to be challenging. The aim of this investigation was to develop an innovative concept in coating sustained-release microparticles using industrial scalable Wurster fluidised bed to produce oral liquid suspensions. Microcrystalline cellulose cores (particle size <150 μm) were coated with Eudragit® NM 30 D and Eudragit® RS/RL 30 D aqueous dispersions using a fluidised bed coater. A novel approach of periodic addition of a small quantity (0.1% w/w) of dry powder glidant, magnesium stearate, to the coating chamber via an external port was applied throughout the coating process. This method significantly increased coating production yield from less than 50% to up to 99% compared to conventional coating
process without the dry powder glidant. Powder rheology tests showed that dry powder glidants increased the tapped density and decreased the cohesive index of coated microparticles. Reproducible microencapsulation of a highly water-soluble drug, metoprolol succinate, was achieved, yielding coated microparticles less than 200 μm in size with 20-h sustained drug release, suitable for use in liquid suspensions. The robust, scalable technology presented in this study offers an important solution to the long-standing challenges of formulating sustained-release dosage forms suitable for children and older people with swallowing difficulties.
Basic Candlestick Pattern in stock market, financeGuru Balaji .S
The document provides information on various candlestick patterns used in technical analysis of financial markets. It begins with definitions of basic candlestick types like doji and hanging man candles. It then outlines several reversal patterns like morning star and engulfing patterns that indicate a change in trend. Continuation patterns like rising three methods and falling three methods that suggest the current trend will persist are also discussed. The document provides illustrations and explanations of many common candlestick patterns to help readers understand how to interpret these visual representations of market price action.
This document outlines various types and uses of purified water in pharmaceutical applications. It discusses drinking water that meets EPA or international standards which can be used directly if compatible. It then lists several typical water treatment steps like deionization, reverse osmosis, and distillation used to produce purified water for special pharmaceutical purposes like API processes. The document categorizes purified water products for uses such as hemodialysis, analytical reagents, cleaning/ingredients for non-parenteral dosage forms, and various sterile purified waters for injection, irrigation, inhalation after additional packaging and sterilization steps.
The document outlines the process for registering a pharmaceutical product in the USA, which includes developing and testing the product, submitting an ANDA application to the FDA for approval, producing validation batches at a larger scale once approved, launching the product commercially, undergoing facility inspections by the FDA periodically for compliance.
This document discusses critical material attributes (CMA), critical process parameters (CPP), and critical quality attributes (CQA) for various pharmaceutical unit operations used in manufacturing oral solid dosage forms. It provides examples of CMAs, CPPS, and CQAs for common processes like blending, granulation, drying, compaction, and tableting. The goal is to identify material traits and processing conditions that most impact the critical quality standards of the finished drugs.
Specifications of process parameters and general ipc and finish product controlsGuru Balaji .S
This document outlines the critical process parameters and quality controls for various stages of manufacturing injectable products. It lists 7 key stages: 1) materials preparation, 2) compounding, 3) filtration, 4) filling, 5) lyophilization (if applicable), 6) final sterilization (if required), and 7) inspection. For each stage, critical process parameters are defined relating to temperature, time, pressure, flow rates, and other factors. Quality attributes of intermediate and finished products are also specified, including assays, pH, bacterial counts, and other attributes to ensure quality.
This document discusses process validation. It defines process validation as establishing documented evidence that a process will consistently produce a product meeting its predetermined specifications. The key aspects of process validation are to obtain consistent and reliable data, demonstrate that the process remains in control, and show the process works as intended. There are different types of process validation including prospective, retrospective, and concurrent validation. Process validation involves multiple phases from process design and qualification to process verification and monitoring. It is important for quality, safety, efficacy and compliance with global regulatory agencies.
The pharmaceutical industry is a key driver of scientific and medical progress. It invests billions annually in research and development to develop new medicines. In Europe, the industry invested an estimated €33.6 billion in R&D in 2015 and directly employs over 745,000 people. However, the industry faces challenges from fiscal austerity in Europe and increasing competition from emerging markets with fast-growing pharmaceutical sectors like Brazil and China.
The document describes the five modules of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Common Technical Document (CTD) format for ASEAN countries. Module 1 contains regional administrative information. Module 2 provides an overall summary of Modules 3, 4, and 5, including quality, non-clinical, and clinical overviews. Module 3 includes chemistry, manufacturing, and quality control documents. Module 4 contains non-clinical safety data. Module 5 provides clinical study reports, though generics only need to include bioequivalence studies. The CTD format is required for both new drug and generic applications in ASEAN countries.
Points to be considered in topical formulation designGuru Balaji .S
This document outlines key points to consider in topical formulation design, including the drug substance, excipients, physicochemical properties, container closure system, chemical and physical stability, manufacturability and scalability, preservative efficacy, and patient acceptance. Some important considerations are the quality and physical characteristics of the active pharmaceutical ingredient and excipients, ensuring compatibility between ingredients, and establishing a target product profile that maintains consistency of the formulation over time. Process parameters and equipment must also be identified during development to enable scalability and reproducibility of the commercial manufacturing process.
The document discusses requirements for new drug applications and abbreviated new drug applications for topical products. A full NDA requires extensive safety studies including toxicity, skin irritation, and sensitization testing as well as two clinical efficacy studies and manufacturing controls. An ANDA for generic topical products requires abbreviated safety testing for skin irritation and toxicity along with manufacturing controls and either in vivo bioequivalence studies or in vitro release testing, and qualitatively and quantitatively matching inactive ingredients.
IND refers to investigational new drugs used in clinical trials. NDA and BLA are for approval of new drugs and biologics respectively, requiring clinical data. ANDA is an abbreviated application for generic drugs, needing bioequivalence data. OTC drugs are approved via monographs without premarket review or the orange/purple book.
Pharmaceutical QbD concepts for drug developmentGuru Balaji .S
The document discusses quality by design (QbD) in pharmaceutical development. It defines QbD as a systematic approach that begins with predefined objectives and emphasizes product and process understanding based on science and risk management. Under QbD, the desired product performance profile, target product quality attributes, and critical material attributes are defined to identify and control sources of variability. QbD provides increased flexibility while maintaining quality standards compared to traditional quality testing approaches. Key aspects of implementing QbD include knowledge management, risk management, designing controls based on scientific understanding, and continual improvement using knowledge gained over a product's lifecycle.
Generic product development with QbD pathwayGuru Balaji .S
This document outlines the key steps for generic drug product development using a Quality by Design (QbD) pathway, including supplier selection, API and excipient compatibility studies, process development from lab to pilot to pivotal scale, formula optimization at each stage, manufacturing demonstration batches, biostudies, stability testing, and e-CTD regulatory submission with defined quality target product profile, critical quality attributes, critical material attributes, and control strategy.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
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TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kol...rightmanforbloodline
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Versio
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
2. ' PHAR MAC EUTICA L COM POSITIONS O F IBUPROF EN AND
PROC ESS T H EREO F.
FIE L D O F T HE INV ENTION:
The present invention relates to pharmaceutical compositions of Ibuprofen or its
pharmaceutically acceptable salt, enantiomers thereof and methods of preparing
them. Particularly, the present invention relates to a cost effective method of
producing stable pharmaceutical compositions of Ibuprofen or its
pharmaceutically acceptable salts, enantiomers thereof. The process of the present
invention particularly involves the use of glidant in three stages of formulation to
obtain free flowing granules that impart better release properties and minimize the
tablet weight variation.
BAC K GROUND O F T H E INV ENTION:
Ibuprofen, chemically known as 2-(4~isobutyl phenyl) propionic acid, is a well-
known medicament or NSAID with anti- inflammatory, antipyretic, and analgesic
activities. Ibuprofen is primarily used for the treatment of pain and inflammation
in musculoskeletal disorders such as rheumatoid arthritis, ankylosing spondylitis,
osteoarthritis, postoperative pain, post partum pain, headache, backache,
neuralgia, dysmenorrhoea, dental pain, colds and flu and soft tissue injuries,
generally at doses up to 3200 mg per day. Ibuprofen and its compositions are
disclosed in US3228831 and US3385886.
Active ingredients with a low melting range, such as ibuprofen or its
pharmaceutically acceptable salts, especially the sodium salt, that is described
as fluffy, soft, sticky, especially poorly compressible and also as having a poor
ability to be granulated, can lead to serious difficulties in the processing of
formulation, as a consequence of sintering processes and through sticking to the
punch and die plates of the tablet press and low tableting speeds. Even during the
mixing process to produce dry ibuprofen or its salt containing mixtures there may
be sticking of the mixing tools especially with a high energy input and heating of
3. the agitators. The sticking can admittedly be rectified by the addition of a large
quantity of anti-sticking agents. However, using said mixing process the end
mixtures become hydrophobic and the release of the active ingredient is slowed
thereby. Problems further arise in the processing of ibuprofen or its
pharmaceutically acceptable salt containing mixtures especially with relatively
low compressive forces too in order to save the high-cost compression tools from
wear. The unwanted phenomenon of adhesion to the compression tools is
observed to persist as the duration of production cycle increases.
Compositions produced by wet granulation method require relatively large
percentages of excipients to produce a compressible formulation, leading to
increase in tablet size which is undesirable both from manufacturing and
handling standpoint and a patient acceptability standpoint.
US4609675 discloses a method of preparing a pharmaceutical ibuprof en-
containing granulate composition suitable for preparing tablets of relatively high
dosage. This is accomplished by dry mixing ibuprofen with 1 to 15 percent by
weight of croscarmellose sodium as disintegrant and small amounts of colloidal
silica with short mixing times in the region of a few minutes, and is subsequently
roll -compacted. Croscarmellose sodium is a relatively expensive additive and it
contributes significantly to the cost of the formulation. A n insufficient
improvement in tablet ability is achieved with these formulations.
US4806358 discloses tablet composition manufactured through aqueous/non-
aqueous granulation comprising ibuprofen or a pharmaceutically acceptable salt
thereof, a pharmaceutically acceptable effervescent couple that produces carbon
dioxide in the presence of water, a pharmaceutically acceptable surfactant, a
pharmaceutically acceptable water-insoluble hydrophilic polymer consisting of
microcrystalline cellulose and croscarmellose sodium and a saccharide, for
example sucrose, lactose, dextrose or sorbitol, to enhance the stability of the
composition dispersed therein. The physico chemical stability of effervescent
4. formulations is relatively less comparable to conventional formulations and need
special precautions and packaging materials.
US4839176 discloses a stable composition comprising ibuprofen or a
pharmaceutically acceptable salt thereof, codeine or a pharmaceutically acceptable
salt thereof together with a sufficient amount of pharmaceutically acceptable
insoluble salt of carboxymethyl cellulose to prevent discoloration of the
composition.. The composition based on ibuprofen and codeine is ineffective and
is not patient compliant.
US4859704 discloses water soluble alkali metal salt (potassium and sodium) of
ibuprofen prepared by reacting ibuprofen and alkali metal bicarbonate in an
aqueous medium. This process of wet granulation involves the evolution of C0 2
gas, which may lead to pressurization inside the reactor which makes the process
less attractive.
US4904477 discloses a spray dried ibuprofen composition suitable for direct
compression into tablets and include a spray dried dispersion in water of
ibuprofen, pregelatinized starch, a disintegrate and a wetting agent. Spray drying
is a complex granulation method, which involves use of high temperatures.
US491 1921 provides a granular pharmaceutical composition containing t
ibuprofen, binder, and polyvinyl pyrrol idone, wherein the polyvinyl pyrrol idone
forms a film with a portion of said binder to form agglomerates. The process for
preparing the tablets includes fluidizing Ibuprofen with a portion of the binder in a
fluid bed apparatus and spraying the aqueous dispersion of polyvinylpyrrolidone
and the remainder of the binder. The granulation may be subsequently blended
with additional excipients and, optionally, additional active pharmaceutical
ingredients for direct compression into tablets. The process requires extra
processing steps involving sophisticated equipment and a relatively high operating
cost.
5. US5191 114 discloses a process for producing ibuprofen powders for direct
tableti ng, in which powders with improved flowability are said to be obtained by
dry mixing of ibuprofen with amorphous silica gel. Direct compressible ibuprofen
particles are also formed by treating commercially available, dry ibuprofen with a
hydrophilic solvent or a mixture of a hydrophilic solvent and one or more
hydrophobic organic solvents so as to change at least the external crystalline
shape of the ibuprofen from a flow- retarding shape to a free-flowing, easily
compressible configuration. A typical hydrophilic solvent is water and among the
hydrophobic solvents which may be used are acetone, methyl alcohol, ethyl
alcohol, isopropyl and N-propyl alcohol. A s is known to the skilled worker, the
flowability can be improved in this way after only a short mixing time. However,
the tablet ability is not improved in practice in this way.
US5445827 relates to an effervescent ibuprofen preparation comprising a) basic
granules consisting of 1 part by weight of water-soluble ibuprofen salt preferably
sodium salt, 2 to 10 parts by weight of excipient, 0.3 to 0.8 part by weight of
stabilizer and 0.1 to 1 part by weight of sodium carbonate or potassium carbonate
and b) 1 to 4 parts by weight of an acid component. The patent did not have the
object to describe (the preparation of) a very water soluble ibuprofen granulates in
an efficient and cheap manner from insoluble ibuprofen. The physico chemical
stability of effervescent formulations is relatively less comparable to conventional
formulations and thus need special precautions and packaging materials.
US5320855 discloses a chewable medicament tablets made from coated
rotogranules of a medicament wherein the rotogranules are formed from a wet
granulation mixture of medicament, e.g. ibuprofen, polyvinylpyrrolidone, sodium
starch glycolate and sodium lauryl sulfate and the rotogranules are coated with
hydroxyl ethyl cellulose or a mixture of hydroxyl ethyl cellulose and hydroxyl
propyl methyl cellulose and a process for making such tablets and a method of
providing taste masking of medicaments utilizing such coated rotogranules in a
tablet. While resulting in a significant taste improvement, this method has been
6. found not to completely eliminate the throat burn_ associated with ibuprofen in
chewabl e dosage forms.
US5696165 discloses the use of the sodium salt of S(+)-ibuprofen dihydrate with
a pharmaceutical composition comprising 10-99% wA/v of S(+)-ibuprofen sodium;
1-90% w/w of a diluent; 0.1-10% w/w of a lubricating agent; 0.1-15% w/w of a
disintegrating agent; optionally 0.1-15% w w of a binder and optionally 0.1-10%
of a flow aid. It permits the preparation of a tablet using wet granulation technique
comprising dissolving polyvinyl pyrrolidone in a mixture of isopropanol and
water (1:1 parts by vol ume).
US61 97336 discloses a tablet composition comprising ibuprofen, arginine, linear
poly vinyl pyrrolidone, and alkaline bicarbonate having good workability and fast
dissolution so as to assure a prompt analgesic effect. The patent states that it is
possible that during preparation of the composition and/or tablets, some
interaction or reaction may occur between two or more components, but it is silent
about the extent and type of such interaction. The tablets containing 200 mg
ibuprofen weigh 600 mg which is rather large for such dosage; tablets containing
400 mg ibuprofen weigh 980 mg which can hardly be swallowed. Moreover, the
large quantity of expensive arginine required significantly increases the costs.
US8846085 discloses a directly tabletable ibuprofen formulation comprising
crystalline ibuprofen; finely divided silica with a surface area of at least 100 rr /g
together with pharmaceutically acceptable excipients wherein at least 50% of the
surface of the ibuprofen crystals is covered with finely divided excipient.
US20020034540 discloses a solid non-effervescent compressed dosage form
comprising ibuprofen combined with a disintegrating component. The
composition comprises a carrier material such as alkali metal carbonate or
bicarbonate in an amount such that the dosage form has a crushing strength in the
range 6.5-15Kp and a disintegration time of less than 10 minutes. The dosage
7. form is supposedly particularly advantageous to the formulation with the poorly
compressible alkali metal salts and especially the sodium salt, that is described as
fluffy, soft sticky, especially poorly compressible and also as having a poor
ability to be granulated. Further US20020034540 discloses the wet granulation
process comprising pre-granulating ibuprofen with a binder, such as polyvinyl
pyrrol idone in water or hydrocarbon solvent.
US20040102522 provides directly compressible dosage form of sodium
ibuprofen and discloses a non -effervescent tablet of ibuprofen, comprising a
tablet core and, if desired, a sugar or film coat, wherein the tablet core, based on
the weight of the tablet core, consists of 50 to 100% by weight sodium ibuprofen
hydrate and 50 to 0% by weight auxiliary material component and contains no
lubricant and no disintegrant, and wherein the sodium ibuprofen hydrate has a
water content of 8 to 6% by weight preferably to 6% by weight, possesses a
sufficient hardness, is comparably small and leads to a particularly rapid increase
in blood level and thereby to an accelerated onset of analgesic effect. However,
the tablets only possess sufficient not optimal hardness and contain large total
sodium content which is not advantageous to patients, especially frequent and
daily users of such over the counter medicaments. Further, crumbling and
breakage of such tablets prior to ingestion may lead to uncertainty as to the dosage
of active ingredient per tablet and core defects, including picking and sticking.
Furthermore, high friability also causes tablet breakage leading to waste during
factory handling.
US20100323005 discloses sodium ibuprofen compositions and methods of
manufacturing tablets and caplets using roller compaction. Tablets made by roll
compaction often show inferior tensile strength compared to tablets prepared by
wet granulation or direct compaction. Because this phenomenon is more profound
in plastic substances, adjusting the plastic/brittle balances of starting materials by
selecting appropriate excipients is much more. Also, minimum compaction force
should be used, as well as a smaller particle size of starting powder is required. A
8. second disadvantage of roll compaction is the production of noniiompacted
powder. Because no liquid binder is used, high amounts of fines remain and less
product yield is obtained.
The problems associated with the prior art compositions of ibuprofen and
processes for preparation include; (a) inadequate bulk density of ibuprofen or its
pharmaceutically acceptable salt granules to obtain a reasonably sized tablet; (b)
punch filming, picking or sticking during compression; (c) obtaining poor
flowing granulation formulation which are difficult to handle in typical
pharmaceutical plant scale equipment; (e) excessive disintegration time,
Lamination and friability problems; (f) using alcohol especially ethanol during
wet granulation requires special equipment which is highly undesirable.
Moreover, because of the high dosage strengths involved, only minimal amounts
of pharmaceutical excipients could be added to overcome the above problems
(i.e., punch filming, poor flow, excessive disintegration times, lamination, etc.) In
addition, besides the above problems facing by an industrial pharmacist or
pharmaceutical engineer, there is the concern that in some cases, the source of
supply of certain types of the bulk ibuprofen or its pharmaceutically acceptable
salt drug per se may not be reliable or dependable.
Therefore a need remains among the industrial pharmacist or pharmaceutical
engineer to provide process conditions, proportions of ingredients in the
manufacturing process of ibuprofen or its pharmaceutically acceptable salt to
obtain a final formulations (i.e., tablets and capsules or caplets) which will
overcome the above problems, acceptable to the pharmaceutical industry,
physicians and the pharmacists and patient populations alike.
The present invention addresses these and other problems associated with the
prior art by providing technically feasible process for manufacturing ibuprofen or
it ' s pharmaceutically acceptable salts, enantiomers thereof, being blended with
9. external excipients to produce a formulation capable of being directly formed into
a tablet or caplet having suitable hardness, short disintegration time and fast
dissolution time. The method provides suitable blending of ibuprofen or i s
pharmaceutically acceptable salts, enantiomers thereof with suitable
pharmaceutically acceptable excipients for tabletization so as to achieve a long
production cycle running for as many hours as possible without compromising on
standards.
OBJ ECT O F T H E INV ENTION:
It is therefore the primary object of the present invention to provide a cost
effective, industrially feasible method of producing stable, formulations of
Ibuprofen or its pharmaceutically acceptable salts or its enantiomers adaptable to
final formulation with varying dosage size having suitable hardness, short
disintegration time and fast dissol ution time.
SUM MA RY O F T H E INV ENTION:
To meet the above objectives, the present invention provides a method/process for
preparing a stable pharmaceutical composition of Ibuprofen or its
pharmaceutically acceptable salts, enantiomers thereof which are adaptable to
final formulations having a variety of dosage forms such as compressed tablets,
caplets and filled capsules with varying dosage size.
In an aspect, the present invention provides a method of preparing stable
pharmaceutical composition of Ibuprofen or its pharmaceutically acceptable salts,
enantiomers thereof, characterized in that the glidant used is added in pre-
blending, blending and lubricating stage of said process; comprising;
(i) Granulating ibuprofen with one or more pharmaceutically acceptable
excipients;
(ii) Milling the granules of step (i) and mixing with glidant to form a pre-
blend mixture;
10. (iii) Blending mixture of step (ii) with one or more pharmaceutically
acceptable excipients and a glidant;
(iv) Lubricating the blend of step (iii) with one or more pharmaceutically
acceptable excipients and glidant,
(v) Formulating the blend obtained in step (iv) into a suitable dosage form;
and
(vi) Optionally coating the dosage form obtained in step (v).
The method of producing said pharmaceutical composition comprises dry
granulation or wet granulation, preferably wet granulation.
The pharmaceutically acceptable excipients for the process are selected from
diluents, binders, disintegrants, glidants, lubricants, surfactants, flavorants, colors,
and such like alone or in combination thereof. The granules obtained by the
process of the present invention are further compressed in to tablets or caplets or
as filled capsules in a suitable dosage size. Optionally, the pharmaceutical
composition of ibuprofen or its pharmaceutically acceptable salts, enantiomers
thereof may contain other suitable active ingredients.
In another aspect, the present invention provides stable pharmaceutical
composition with short disintegration time and increased dissolution rate without
being unacceptably friable comprising;
i. Ibuprofen or its pharmaceutically acceptable salts, enantiomers
thereof, in an amount of about 40 percent or more on a dry weight
basis;
ii. one or more pharmaceutically acceptable fillers/diluents in an
amount of about 20 percent or more on a dry weight basis;
iii. one or more pharmaceutically acceptable wetting agents/surfactants
in an amount of about 0.1 percent or more on a dry weight basis;
iv. one or more pharmaceutically acceptable disintegrants in an amount
of about 3 percent or more on a dry weight basis;
11. v . one or more pharmaceutically acceptable binders in a binding
amount of about 2 percent or more on a dry weight basis;
vi. one or more pharmaceutically acceptable lubricants in an amount of
about 1 percent or more on a dry weight basis; and
vii. one or more pharmaceutically acceptable glidants in an amount of
about 1 percent or more on a dry weight basis.
D ETAIL ED D ESC RIPTION O F T H E INV ENTION:
The present invention relates to novel pharmaceutical granulation, comprising
ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof, having
specific advantageous properties including (a) excellent physical stability,
especially regarding compressed tablets dissolution properties, (b) high bulk
density, (c) excellent bioavailability and (d) excellent processing properties in
pharmaceutical plant equipment including good flowability, no sticking or picking
during compression process or filling into capsules.
The ingredients and processes set forth herein allow for the manufacture of tablets
and caplets or capsules with advantageous characteristics including rapid
dissolution and excellent tablet strength. A s used herein, the word tablets is
intended to comprise tablets, caplets, capsule shaped tablets, pills or any other
synonym thereof. Further, tablet refers to a pharmacological composition in the
form of a small, essentially solid pellet of any shape. Tablet shapes maybe
cylindrical, spherical, rectangular, capsular, or irregular.
A s used herein, the term ' about (or ' approximately ) means a particular value
can have a range acceptable to those of ski 11in the art given the nature of the val ue
and method by which it is determined.
In an embodiment, the present invention discloses a method of preparing stable
granular pharmaceutical composition of Ibuprofen or its pharmaceutically
acceptable salts, enantiomers thereof, characterized in that the glidant used is
12. added in pre-blending, blending and lubricating stage of said process;
comprising;
i. Granulating ibuprofen with one or more pharmaceutically acceptable
excipients;
ii. Milling the granules of step (i) and mixing with glidant to form a pre-
blend mixture;
iii. Blending mixture of step (ii) with one or more pharmaceutically
acceptable excipients and a glidant;
iv. Lubricating the blend of step (iii) with one or more pharmaceutically
acceptable excipients and glidant,
v . Formulating the blend obtained in step (iv) into a suitable dosage form;
and
v i. Opti onal ly coati ng the dosage form obtai ned in step (v)
The method or process of producing said pharmaceutical composition comprises
dry granulation or wet granulation, preferably wet granulation. The solvents for
wet granulation are selected from water, isopropyl alcohol, ethanol and/or
mixtures thereof.
The pharmaceutically acceptable excipients for the process are selected from
diluents/fillers, binders, disintegrants, glidants, lubricants, surfactants, flavoring
agnets, colors, lubricants, souring agents, sweeteners, and wetting
agents/surfactants and such like alone or in combination thereof.
The glidants are used in the present invention to improve the flow of the powder
blend, to impart better mold release properties and minimize tablet weight
variation. The Glidant is selected from the group comprising of talc, silicon
dioxide, silicic acid, cornstarch, maize starch or starch derivatives, calcium
silicate, magnesium carbonate, magnesium oxide, magnesium silicate, colloidal
silicon dioxide, starch, castor wax and combination thereof. Those of ordinary
skill will further appreciate that other glidant could be added or substituted to
13. formulate the compositions contemplated herein. The glidants are used in an
amount ranging from 0.1 to 30%.
The binder used in the present granulation refers to one or more ingredients added
before or during granulation to form granules and/or promote cohesive compacts
during compression. Thus, the binder component of the present granulation serves
to impart good binding and disintegrant properties to the final dosage forms
prepared from the granulation, i.e., tablets. It is included in an amount effective
for imparting to the granulation and formulations made there from, the capability
of being formed into tablets having optimum hardness, disintegration time, and
short dissolution time when compared against marketed one. Binders of the
present invention is selected from starches and starch derivatives, celluloses,
sugars, polymers like pregelatinized starch, corn starch, microcrystalline cellulose,
lactose, sucrose, mannitol, silicon dioxide, vinyl pyrrolidone vinyl acetate
copolymers, polyvinyl alcohol based compositions, hydroxyl propyl
methyl cellulose, hydroxyl propyl cellulose, methyl cellulose, ethyl cellulose,
hydroxyl ethyl cellulose, carboxymethyl cellulose and natural gums (e.g., gum
acacia, gum tragacanth, etc.) and synthetic polymer binders like
polyvinylpyrrolidone, hydrocolloids, sugars, povidone, copovidone, methacrylic
acid copolymers and combination or compatible mixtures of two or more such
materials in the range of 0.1 to 20%w/w.
Diluent/filler used in the present invention generally are auxiliary materials that
improve the compressi biIity. Preferably the diIuents/fi11ers are sel ected that neutral
to weakly acidic and can improve the compressibility which include cellulose
and its derivatives like microcrystalline cellulose, silicified microcrystalline
cellulose, powdered cellulose, carbohydrates and polyalcohol such as lactose,
sucrose, dextrose, saccharose, glucose, fructose, xylitol, mannitol, sorbitol,
lactitol, maltitol, starch, modified starches, hydrolysed or enzymatically split
starch such as maltodextrin, cyclodextrins such as §- and .-.cyclodextrin, non-
cross linked (water soluble) polyvinylpyrrolidone, polyvinyl alcohols,
14. polyethylene glycols, polypropylene glycols, alkali metal salts, alkaline earth
metal salts and ammonium salts of organic or inorganic acids, in particular
sodium, potassium, magnesium and calcium salts such as sodium chloride,
potassium chloride, magnesium chloride, sodium sulphate, potassium sulphate,
magnesium sulphate, tri magnesium dicitrate, tricalcium dicitrate, calcium lactate,
calcium gluconate, calcium hydrogen phosphate, dicalcium phosphate, tri basic
calcium phosphate, magnesium carbonate, magnesium oxide, talc, or combination
thereof. T he diIuent (s) are present in the range from 0.1 to 80%.
Disintegrant, which provide superior bioavailability of the medicament in the
granulations include but is not limited to cross linked vinylic polymers such as
cross-linked polyvinylpyrrolidone (crospovidone), polyvinyl pyrrolidine or
sodium starch glycolate. Other useful disintegrants may comprise derivatives of
starch and of cellulose such as sodium carboxy methyl-starch and cross linked
sodium carboxy methyl cellulose (croscarmellose sodium), cross linked calcium
carboxy methyl cellulose, microcrystalline cellulose, carboxy methyl cellulose,
hydroxyl propyl cellulose, low-substituted hydroxyl propyl cellulose, alginic acid,
sodium alginate, potassium alginate, calcium alginate, an ion exchange resins,
calcium silicate, a metal carbonate, sodium bicarbonate, calcium citrate, or
calcium phosphate starch and modified starches including pregelatinized starch,
formal in-casein, alginates, gums and combination or and mixtures thereof. The
disintegrant is present in the range from 0.1 to 30%.
Sodium lauryl sulfate (SLS) is a surfactant which aids in the wetting of the
granules in the body thereby increasing the disintegration of the tablet and release
rate of ibuprofen or other water insoluble medicaments. SLS is a surfactant with a
very high HLB (hydrophi Iic-l ipophi Iic balance) number and its use obtains good
wetting and rapid dissolution of the medicament granulation of the invention.
Other useful surfactants may include cationic, anionic and nonionic surfactants,
sodium lauryl sulfate, monooleate, monolaurate, monopalmitate, monostearate or
another ester of polyoxyethylene sorbitane, sodium dioctylsulfosuccinate, lecithin,
15. stearylic alcohol, cetostearylic alcohol, cholesterol, polyoxyethylene ricin oil,
polyoxyethylene fatty acid glycerides, poloxamer, potassium and sodium oleates
and polysorbates. T he surfactants are used in the range of 0.1 to 10%
Additionally, and optionally, other substances commonly used in pharmaceutical
formulations can be included such as flavors (e.g., burnt sugar flavor, strawberry
aroma, raspberry aroma, cherry flavor, magnasweet 135, key lime flavor, grape
flavor, fruit extracts and prosweet), flavor enhancers and sweeteners (e.g.,
sucralose, aspartame, sodium saccharine, sorbitol, glucose, sucrose), souring
agents (e.g. citric acid), dyes or colorants.
In another embodiment the present invention relates to a method/process of
preparing a stable pharmaceutical composition of Ibuprofen or its
pharmaceutically acceptable salts, enantiomers thereof, wherein the glidant used is
added in pre-blending, blending and lubricating stage of said process;
comprising;
i. Granulating ibuprofen with one or more pharmaceutically acceptable
excipients;
ii. Milling the granules of step (i) and mixing with glidant in an amount of
about .5%w/w to form a pre-blend mixture;
iii. blending mixture of step (ii) with one or more pharmaceutically acceptable
excipients and a glidant in an amount of about .0%w/w;
iv. lubricating the blend of step (iii) with one or more pharmaceutically
acceptable excipients and glidant in an amount of about 0.5%w/w,
v . formulating the blend obtained in step (iv) into a suitable dosage form; and
v i. opti onal ly coati ng the dosage form obtai ned in step (v) .
The granulation thus produced could be directly compressed to form tablets.
However, better tablets are produced by blending the granulation by known
methods, such as using double cone blender, with additional excipients that aid in
the compression and provide improved properties such as hardness and excellent
16. disintegration time. These excipients may be selected from the whole range
known in the art and are chosen in the present invention based on the desired
properties of the tablet produced.
It is highly desirable to add a lubricant that aids in the production of the tablets to
facilitate ejection of the finished tablet from dies after compression and to prevent
tablets from sticking to punch faces and each other. Examples of such lubricants
are stearic acid, metal stearates like calcium/magnesium/sodium stearate, sodium
stearyl fumarate, leucine, glycerol behenate, sodium benzoate, talc, silicon
dioxide, silicic acid, colloidal silicon dioxide, mineral oil, fumaric acid, sodium
stearyl fumarate, stearic acid, talc, vegetable oil, castor wax and combination
thereof and polyethylene glycol, poloxamers, sodium lauryl sulfate, micro
crystalline cellulose and hydrogenated vegetable oils. Those of ordinary skill will
further appreciate that other lubricants could be added or substituted to formulate
the compositions contemplated herein. The lubricants are used in an amount
ranging from 0.1 to 10%.
The pharmaceutical granules of ibuprofen or its pharmaceutically acceptable salts
or enantiomer thereof obtained by the process of the present invention is further
compressed in to tablets or caplets or as filled capsules and can be formulated in
dosage size ranging from 100 to 1200mg per dosage unit.
In another embodiment, the present invention discloses stable pharmaceutical
composition with short disintegration time and increased dissolution rate without
being unacceptably friable comprising;
i. Ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof, in
an amount of about 40 percent or more on a dry weight basis;
ii. one or more pharmaceutically acceptable fillers in an amount of about 20
percent or more on a dry weight basis;
iii. one or more pharmaceutically acceptable wetting agents/surfactants in an
amount of about 0.1 percent or more on a dry weight basis;
17. iv. one or more pharmaceutically acceptable disintegrants in an amount of
about 3 percent or more on a dry weight basis;
v . one or more pharmaceutically acceptable binders in a binding amount of
about 2 percent or more on a dry weight basis;
vi. one or more pharmaceutically acceptable lubricants in an amount of about
1 percent or more on a dry weight basis; and
vii. one or more pharmaceutically acceptable glidants in an amount of about
1 percent or more on a dry weight basis.
According to one embodiment the pharmaceutical composition comprises a coated
core having at least one coating, comprising a sugar or film coating with
pharmaceutically acceptable coating agents, in which all customary sugar and film
coating materials are in principle suitable as coating materials. The thickness of
the coat is not critical; however in general the proportion of the coat, based on the
weight of the tablet core, is only about 1 to 25% by weight, preferably about 2 to
6% by weight.
In a preferred embodiment, the stable pharmaceutical composition with short
disintegration time and increased dissolution rate without being unacceptably
friable comprises;
i. Ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof, in
an amount of about 50 percent or more on a dry weight basis;
ii. about 20 percent or more a pharmaceutically acceptable filler preferably
lactose on a dry weight basis;
iii. about 0.1 percent or more a pharmaceutically acceptable surfactant
preferably sodium lauryl sulphate on a dry weight basis;
iv. about 3 percent or more a pharmaceutically acceptable disintegrant
preferably crospovidone or its derivatives on a dry weight basis;
v . about 2 percent or more a pharmaceutically acceptable binder preferably
poly vinyl pyrrolidone or its derivatives on a dry weight basis;
18. vi. about 1 percent or more a pharmaceutically acceptable lubricant preferably
a metal stearate on a dry weight basis; and
vii. one or more pharmaceutically acceptable glidants in an amount of about 1
percent or more on a dry weight basis.
In another aspect, the method of preparing the granulation described by a wet
granulation method comprises, Sifting the composition components of the present
invention selected from diluent, surfactant, disintegrant including Ibuprofen or its
pharmaceutically acceptable salts and dry mixing for not less than 5 minutes.
Granulating the dry mix in RMG using binder solution prepared using water or
alcoholic or hydro-alcohol. Drying the resulting granules using FBD followed by
milling/sizing and mixing the granules with a part of glidant for not less than 10-
20minutes. Further blending with diluent, disintegrant and a part of the glidant of
not Iess than 3- 0 minutes. Lubri cati ng the f inal blend of not Iess than 2-6 minutes
using lubricant and a final part of the glidant. The manufacturing process of the
present invention involves the use of glidant in three stages of formulation i.e. pre-
blending, blending and lubrication and at 1.5, 1.0 and 0.5%w approximately
respectively.
The amounts of the added excipients are preferably the minimum amounts
necessary to accomplish their purposes. For example, the lubricant component is
present in a lubricating amount sufficient to impart mold release properties to
tablets formed from the formulation and preferably insufficient to increase
disintegration time and dissolution time of such tablets, and preferably insufficient
to decrease the hardness obtainable for tablets formed from a formulation having
no additional lubricant.
The final drug forms (resulting from the new granulation formulations) will have
specific advantageous properties including (a) excellent physical stability,
especially regarding compressed tablet s dissolution properties, (b) high bulk
density (c) excellent bioavailability and (d) excellent processing properties in
19. pharmaceutical plant equipment including good flowability, minimal tablet punch
or plunger sticking during compressing or capsule filling and good compression
characteristics.
The composition of the present invention obtained by the process exhibits a
significant improvement in dissolution profile and assay during stability in stress
and accelerated condition as compared to marketed formulation.
EXAM PL ES
Example 1:
Example 2:
Ingredients % Concentration
Ibuprofen Sodium 55.65
Lactose monohydrate 24.78
Sodium lauryl sulphate 0.25
Crospovidone 9.78
Polyvinyl pyrrol idone 2.93
Isopropyl alcohol Qs
Silicon dioxide 4.16
Talc 0.98
Magnesium stearate 1.47
20. Example 3:
Example 4:
Example 5: Wet granulation method of producing the Ibuprofen granules
Sifted Ibuprofen sodium dihydrate, Lactose monohydrate, Sodium lauryl sulphate,
Crospovidone through mesh. Prepared the binder solution with povidone and
Isopropyl alcohol. Loaded the sifted Ibuprofen sodium dihydrate, lactose
monohydrate, Sodium lauryl sulphate, crospovidone into Rapid Mixer Granulator
(RMG) and mixed for 10 minutes. Granulated the dry mix using povidone binder
solution. Dried the granules in Fluid Bed Drier (FBD) followed by Sizing &
21. milling. Pre-blended the silicon dioxide and dried granules into blender and mixed
for 15 minutes at10e1 RPM. Sifted lactose monohydrate, crospovidone, silicon
dioxide and talc and added to pre blended mixture, were mixed for 8 minutes at
10e1 RPM. Lubricated the blend mixture with magnesium stearate and silicon
dioxide for 3 minutes at 10e1 RPM. The granules obtained were then compressed
in to tablets by a process known in the art. Coating was carried with known
coating agents.
Similar procedure was conducted to obtain the pharmaceutical granules of
example 2, example 3 and example 4 respectively.
Any patents or publications mentioned in this specification are indicative of the
levels of those skilled in the art to which the invention pertains. Further, these
patents and publications are incorporated by reference herein to the same extent as
if each individual publication was specifically and individually incorporated by
reference. One skilled in the art will appreciate readily that the present invention
is well adapted to carry out the objects and obtain the ends and advantages
mentioned, as well as those objects, ends and advantages inherent herein. Changes
therein and other uses which are encompassed within the spirit of the invention as
defined by the scope of the claims will occur to those ski Iled in the art.
22. W e claim,
1. A method of preparing stable pharmaceutical composition of Ibuprofen or
its pharmaceutically acceptable salts, enantiomers thereof, characterized in
that the glidant used is added in pre-blending, blending and lubricating
stage of said process; comprising;
i. Granulating ibuprofen with one or more pharmaceutically
acceptable excipients;
ii. Milling the granules of step (i) and mixing with glidant to form a
pre-blend mixture;
iii. Blending mixture of step (ii) with one or more pharmaceutically
acceptable excipients and a glidant
iv. Lubricating the blend of step (iii) with one or more
pharmaceutically acceptable excipients and glidant;
v . Formulating the blend obtained in step (iv) into a suitable dosage
form; and
vi. Optionally coating the dosage form obtained in step (v).
2. The method according to claim 1, wherein pharmaceutically acceptable
excipients are selected from diluents, binders, disintegrants, glidants,
lubricants, surfactants, wetting agents, colorants, flavorants and the like in
combi nati on thereof.
3. The method according to claim 2, wherein the diluent is selected from the
group consisting of lactose, sucrose, fructose, dextrose, mannitol, sorbitol,
xylitol, lactitol, starch, modified starches, dibasic calcium phosphate,
tri basic calcium phosphate, magnesium carbonate, magnesium oxide, talc,
powdered cellulose, microcrystalline cellulose, silicified microcrystalline
cellulose and combination thereof in an amount ranging from 0.1 to
80%w/w.
4. The method according to claim 2, wherein the binder is selected from the
group consisting of ethyl cellulose, hydroxypropyl cellulose,
hydroxypropyl methyl cellulose, methyl cellulose and hydroxyethyl
23. cellulose, carboxymethyl cellulose, starch and its derivatives, polyvinyl
alcohol, polyvinyl alcohol based compositions, hydrocolloids, sugars,
polyvinyl pyrrol idone, povidone, copovidone, methacrylic acid
copolymers and combination thereof in an amount ranging from 0.1 to
20%w/w.
5. T he method accordi ng to claim 2, wherei n the disintegrant is sel ected from
the group comprising of low-substituted hydroxy propyl cellulose,
hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, polyvinyl
pyrrolidine, cross-linked sodium carboxymethyl cellulose, cross-linked
calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, calcium
carboxy methyl cellulose, microcrystalline cellulose, croscarmellose
sodium, sodium starch glycolate, ion-exchange resins, starch and modified
starches including pregelatinized starch, formalin-casein, alginates, gums
and combination thereof in an amount ranging from 0.1 to 20%.w/w.
6. The method according to claim 2, wherein the glidant is selected from the
group comprising of talc, silicon dioxide, silicic acid, cornstarch, maize
starch, calcium silicate, magnesium carbonate, magnesium oxide,
magnesium silicate, colloidal silicon dioxide, starch, castor wax and
combination thereof in an amount ranging from 0.1 to 30%.w/w.
7. The method according to claim 2, wherein the lubricant is selected from
the group comprising of calcium stearate, glycerol behenate, sodium
benzoate, magnesium stearate, silicon dioxide, silicic acid, colloidal
silicon dioxide, zinc stearate, mineral oil, polyethylene glycol, sodium
lauryl sulphate, fumaric acid, sodium stearyl fumarate, stearic acid, talc,
vegetable oil, castor wax and combination thereof in an amount ranging
from 0.1 to 10%.w/w.
8. The method according to claim 2, wherein the surfactant is selected from
the group comprising cationic, anionic and nonionic surfactants, sodium
lauryl sulfate, monooleate, monolaurate, monopalmitate, monostearate or
another ester of polyoxy ethylene sorbitane, sodium dioctylsulfosuccinate,
lecithin, stearyl ic alcohol, cetostearylic alcohol, cholesterol,
24. polyoxyethylene ricin oil, polyoxyethylene fatty acid glycerides,
poloxamer, or a mixture of two or more thereof in an amount ranging
from 0.1 to 10%.w/w.
9. A method of preparing a stable pharmaceutical composition of Ibuprofen
or its pharmaceutically acceptable salts, enantiomers thereof, wherein the
glidant used is added in pre-blending, blending and lubricating stage of
said process; comprising;
i. Granulating ibuprofen with one or more pharmaceutically
acceptable excipients;
ii. Milling the granules of step (i) and mixing with glidant in an
amount of about .5%w/w to form a pre-blend mixture;
iii. Blending mixture of step (ii) with one or more pharmaceutically
acceptable excipients and a glidant in an amount of about
.0%w/w;
iv. Lubricating the blend of step (iii) with one or more
pharmaceutically acceptable excipients and glidant in an amount
of about 0.5%w/w;
v . Formulating the blend obtained in step (iv) into a suitable dosage
form; and
vi. Optionally coating the dosage form obtained in step (v).
10. The method according to claim 1 or 9, wherein the method comprises wet
granulation or dry granulation.
. The method according to claim 10, wherein the solvent for wet
granulation selected from water, isopropyl alcohol, ethanol and/or
mixtures thereof.
12. The pharmaceutical composition of ibuprofen or its pharmaceutically
acceptable salts, enantiomers thereof together with pharmaceutically
acceptable excipients prepared by the process according to claim .
25. nternat ona app cat on o.
PCT/IN2016/050337
A CLASSIFICATION OF SUBJECT MATTER
A61K3 1/00, A61Q1 3/00, D01G1 3/00 Ver sion=2 017 .01
According to International Patent Classification (IPC) or to both national classification and IPC
B FIELDS SEARCHED
Minimum documentation searched (classification system followed by classification symbols)
A61Q 13/00, D01G 13/00, A61K31/00
Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched
Electronic data base consulted during the international search (name of data base and, where practicable, search terms used)
Patseer, IPO Internal Database
C. DOCUMENTS CONSIDERED TO BE RELEVANT
Category* Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No
US20020034540 A l (THE BOOTS COMPANY PLC) 28Aug, 1-12
1997 (28.08.1998)
Page 5 , para[0048]; page 4 para [0026]
CA2063141 A l (MCNEIL PPC INC) 180ct, 1992 1-12
(18 .10 .1992)
abstract
US5445827 A (FRITSCH, ET AL .) 29Aug, 1-12
(29.08.1995) claims
Further documents are listed in the continuation of Box C. See patent family annex
* Special categories of cited documents: later document published after the international filing date or priority
"A" document defining the general state of the art which is not considered date and not in conflict with the application but cited to understand
to be of particular relevance the principle or theory underlying the invention
"E" earlier application or patent but published on or after the international document of particular relevance; the claimed invention cannot be
filing date considered novel or cannot be considered to involve an inventive
"L" document which may throw doubts on priority claim(s) or which is step when the document is taken alone
cited to establish the publication date of another citation or other
speciai reason (as specified) document of particular relevance; the claimed invention cannot be
considered to involve an inventive step when the document is
"O" document referring to an oral disclosure, use, exhibition or other combined with one or more other such documents, such combination
means being obvious to a person skilled in the art
"P" document published prior to t international filing date but later than document member of the same pate family
the priority date claimed
Date of the actual completion of the international Date of mailing of the international search report
27-02-2017 27-02-2017
Name and mailing address of the ISA/ Authorized officer
Indian Patent Office Ravi Kumar Battini
Plot No. 32, Sector 14,Dwarka, ew Delhi-110075
Facsimile No. Telephone No. +91-1125300200
Form PCT/ISA/210 (second sheet) (January 2015)
26. International application No.
Information on patent family members
PCT/IN2016/050337
Citation Pub. Date Family Pub. Date
US 20020034540 A l 28-08-19 WO 1997030699 A2 28-08-1997
EP 0881899 Bl 18-08-2004
CA 2063141 A l 08-10- 1992 US 5320855 A 14-06-1994
US 5445827 A 29-08- 1995 EP 0369228 Bl 18-12-1991
CA 2002732 A l 12-05-1990
Form PCT/ISA/210 (patent family annex) (January 2015)