The document summarizes a study that investigated the effect of conjugating different polymers on the properties of buccal films containing the drug losartan potassium. Sodium alginate and chitosan were conjugated with cysteine and thioglycolic acid respectively, and films containing plain or conjugated polymers were prepared and evaluated. The conjugation was confirmed using FTIR and the polymers were found to contain thiol groups. Films were evaluated for properties like thickness, drug content, swelling, bioadhesion and drug permeation. Formulations containing conjugated polymers showed higher bioadhesion, swelling and longer drug permeation compared to films with plain polymers. The optimized formulations were found to be stable.
This document discusses using gelatin beads as a sustained release drug delivery system. Gelatin beads can provide sustained release of drugs over time by taking advantage of their large surface area and diffusion properties. The document describes preparing and evaluating propranolol HCl loaded gelatin beads using natural polymers gelatin and fish gelatin crosslinked with glutaraldehyde. The beads were evaluated for loading efficiency, yield, in vitro drug release, and stability over 3 months of accelerated conditions. Overall, the document proposes that gelatin beads can serve as a biocompatible drug delivery system for sustained drug release.
Formulation and evaluation ofmetformin HCl micro beads by ionotropic gelation...Sagar Savale
The Metformin HCL Micro Beads is formulated by the Ionotropic Gelation Method. The CMC is a Swellable
polymer is responsible for the Sustained release action or activity. A combination of CMC (Carboxy Methyl
Cellulose) and Sodium Alginate shows better sustained release activity. The PreparedSustained released Micro
Beadsis Evaluated In terms of bulk density, tapped density, angle of repose, Carr’s Index, Swelling Index, Drug
Content, % Encapsulation Efficiency and vitro study. The result associated in Optimized batch is good to
Satisfactory and having a good free flowing property. The Drug Content and % Encapsulation Efficiency values are
within the pharmacopeia limit. The in vitro Dissolution studies shows Maximum percentage of release of drug
(71.15) with in end of 4 Hours.
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 .
The document describes the development of calcium alginate beads for oral delivery of the antibiotic ceftriaxone sodium. Twelve formulations of calcium alginate beads were developed using an ionotropic gelation method. The optimized formulation achieved high drug entrapment efficiency (>75%) and provided sustained drug release over 10-18 hours. Scanning electron microscopy indicated the coated optimized beads had a smooth surface and fewer pores, slowing the drug release rate compared to uncoated beads. The calcium alginate beads have potential as a drug delivery system for oral administration of ceftriaxone sodium.
DEVELOPMENT & EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE MALEATERam C Dhakar
This document summarizes the development and evaluation of mucoadhesive microspheres for the controlled release of pioglitazone maleate. Mucoadhesive microspheres were prepared using sodium carboxymethyl cellulose (SCMC), carbopol 934P (CP), and sodium alginate (SA) as polymers via an emulsification solvent evaporation method. The microspheres were evaluated for particle size, drug entrapment efficiency, mucoadhesion, and in vitro drug release. Microspheres containing SCMC showed the smoothest surface, highest mucoadhesion and drug release over 10 hours. Overall, the study developed pioglitazone-loaded microspheres for controlled
The document discusses key concepts in preformulation studies for drug development. Preformulation involves characterizing important physical and chemical properties of drug molecules like particle size, solubility, polymorphism, and stability. These properties influence dosage form design and development. The document outlines several properties that must be evaluated such as partition coefficient, hydrolytic degradation potential, and drug-excipient interactions to optimize formulation.
ABSTRACT Gliclazide microspheres were prepared by ionotropic gelation method using bioadhesive polymers such as sodium alginate, carbopol 934, carbopol 971, HPMC K4M in different ratios. Totally twelve different formulations of gliclazide were prepared by using the above polymers. The microspheres were characterized for drug content, entrapment efficiency, swelling index, mucoadhesive property by In vitro wash-off test and in-vitro drug release. The results of this investigation indicate that ionic cross linking technique Ionotropic gelation method can be successfully employed to fabricate Model drug microspheres. Micrometric studies revealed that the mean particle size of the prepared microspheres was in the size range of 512-903 μm and are suitable for bioadhesive microspheres for oral administration. The in-vitro mucoadhesive study demonstrated that microspheres of Model drug using sodium alginate along with Carbopol 934 as copolymer adhered to the mucus to a greater extent than the microspheres of Model drug using sodium alginate along with Carbopol 971 and HPMC K4Mas copolymers. Analysis of drug release mechanism showed that the drug release from the formulations followed non-Fickian diffusion and the best fit model was found to be Korsmeyer-Peppas. Based on the results of evaluation tests formulation coded T4 was concluded as best formulation. Keywords: Bioadhesive Microspheres, Gliclazide, Ionotropic gelation method.
This document discusses using gelatin beads as a sustained release drug delivery system. Gelatin beads can provide sustained release of drugs over time by taking advantage of their large surface area and diffusion properties. The document describes preparing and evaluating propranolol HCl loaded gelatin beads using natural polymers gelatin and fish gelatin crosslinked with glutaraldehyde. The beads were evaluated for loading efficiency, yield, in vitro drug release, and stability over 3 months of accelerated conditions. Overall, the document proposes that gelatin beads can serve as a biocompatible drug delivery system for sustained drug release.
Formulation and evaluation ofmetformin HCl micro beads by ionotropic gelation...Sagar Savale
The Metformin HCL Micro Beads is formulated by the Ionotropic Gelation Method. The CMC is a Swellable
polymer is responsible for the Sustained release action or activity. A combination of CMC (Carboxy Methyl
Cellulose) and Sodium Alginate shows better sustained release activity. The PreparedSustained released Micro
Beadsis Evaluated In terms of bulk density, tapped density, angle of repose, Carr’s Index, Swelling Index, Drug
Content, % Encapsulation Efficiency and vitro study. The result associated in Optimized batch is good to
Satisfactory and having a good free flowing property. The Drug Content and % Encapsulation Efficiency values are
within the pharmacopeia limit. The in vitro Dissolution studies shows Maximum percentage of release of drug
(71.15) with in end of 4 Hours.
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 .
The document describes the development of calcium alginate beads for oral delivery of the antibiotic ceftriaxone sodium. Twelve formulations of calcium alginate beads were developed using an ionotropic gelation method. The optimized formulation achieved high drug entrapment efficiency (>75%) and provided sustained drug release over 10-18 hours. Scanning electron microscopy indicated the coated optimized beads had a smooth surface and fewer pores, slowing the drug release rate compared to uncoated beads. The calcium alginate beads have potential as a drug delivery system for oral administration of ceftriaxone sodium.
DEVELOPMENT & EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE MALEATERam C Dhakar
This document summarizes the development and evaluation of mucoadhesive microspheres for the controlled release of pioglitazone maleate. Mucoadhesive microspheres were prepared using sodium carboxymethyl cellulose (SCMC), carbopol 934P (CP), and sodium alginate (SA) as polymers via an emulsification solvent evaporation method. The microspheres were evaluated for particle size, drug entrapment efficiency, mucoadhesion, and in vitro drug release. Microspheres containing SCMC showed the smoothest surface, highest mucoadhesion and drug release over 10 hours. Overall, the study developed pioglitazone-loaded microspheres for controlled
The document discusses key concepts in preformulation studies for drug development. Preformulation involves characterizing important physical and chemical properties of drug molecules like particle size, solubility, polymorphism, and stability. These properties influence dosage form design and development. The document outlines several properties that must be evaluated such as partition coefficient, hydrolytic degradation potential, and drug-excipient interactions to optimize formulation.
ABSTRACT Gliclazide microspheres were prepared by ionotropic gelation method using bioadhesive polymers such as sodium alginate, carbopol 934, carbopol 971, HPMC K4M in different ratios. Totally twelve different formulations of gliclazide were prepared by using the above polymers. The microspheres were characterized for drug content, entrapment efficiency, swelling index, mucoadhesive property by In vitro wash-off test and in-vitro drug release. The results of this investigation indicate that ionic cross linking technique Ionotropic gelation method can be successfully employed to fabricate Model drug microspheres. Micrometric studies revealed that the mean particle size of the prepared microspheres was in the size range of 512-903 μm and are suitable for bioadhesive microspheres for oral administration. The in-vitro mucoadhesive study demonstrated that microspheres of Model drug using sodium alginate along with Carbopol 934 as copolymer adhered to the mucus to a greater extent than the microspheres of Model drug using sodium alginate along with Carbopol 971 and HPMC K4Mas copolymers. Analysis of drug release mechanism showed that the drug release from the formulations followed non-Fickian diffusion and the best fit model was found to be Korsmeyer-Peppas. Based on the results of evaluation tests formulation coded T4 was concluded as best formulation. Keywords: Bioadhesive Microspheres, Gliclazide, Ionotropic gelation method.
Application of preformulation consideration in the development ofArpan Dhungel
This document discusses preformulation studies for developing parenteral dosage forms. Preformulation involves studying a new drug's physicochemical properties to create stable, effective formulations. Key aspects of preformulation include assessing solubility through methods like changing pH, adding co-solvents or complexing agents, and evaluating stability under various conditions like heat, light and pH to determine a drug's degradation profile. The goal of preformulation is to obtain information to guide formulation development and ensure the drug molecule is most stable.
This document summarizes a study that used the liquisolid technique to enhance the dissolution rate of the poorly water soluble drug ketoprofen. Several liquisolid tablet formulations were prepared using ketoprofen as the drug and propylene glycol or tween 80 as liquid vehicles. Microcrystalline cellulose and dicalcium phosphate were used as carriers and silica gel as the coating material. The liquisolid tablets showed improved flow properties and higher drug release compared to marketed ketoprofen tablets. X-ray diffraction and FTIR analysis indicated no drug-excipient interactions. The liquisolid technique was effective in enhancing the dissolution of the poorly soluble drug ketoprofen.
This document provides an overview of preformulation studies for semisolid dosage forms. It begins with defining preformulation as the investigation of a drug substance's physical and chemical properties alone and when combined with excipients. The objectives of preformulation are to develop a safe, effective, stable pharmaceutical dosage form and to understand a drug's properties before formulation development. Key physicochemical parameters discussed include penetration, solubility, texture analysis, effect of light, salt formation, degradation pathways, partition coefficient, and hygroscopicity. The document concludes that preformulation is an important first step in rational dosage form development.
Cubosomal nanoparticles as an ocular delivery system of fluconazoleSidharth Mehta
The optimized cubosomal dispersion exhibited spherical nanosized particles and reasonable EE% along with higher
FCZ corneal permeation (twofold) as compared to that of FCZ solution.
Moreover, the in vivo study proved the efficacy and safety FCZ-loaded
cubosomal dispersion in treatment of induced keratomycosis
in rats compared to aqueous FCZ solution after topical ocular
application.
Based on the previous results, the use of
cubosomal dispersion as an ocular drug delivery system is
expected to improve antifungal activity of FCZ in treatment
of fungal keratitis.
This document summarizes a study on enhancing the dissolution rate of olanzapine, an antipsychotic drug with poor water solubility, using solid dispersion techniques. The study aimed to prepare solid dispersions of olanzapine with various carriers using physical mixture, solvent evaporation, and kneading methods. Dissolution tests found that the solid dispersions significantly increased the dissolution rate of olanzapine compared to the raw drug. Carriers like PEG 4000, PEG 6000, and HP-βCD were most effective at enhancing dissolution when prepared by the kneading or solvent evaporation methods. FT-IR analysis was used to evaluate drug-carrier interactions. The results of this study demonstrate that solid dispersion is an
This document discusses the importance of rheology in developing pharmaceutical formulations. Rheology considers how materials deform under stress, which directly impacts how drugs are formulated and how patients use medications. Viscosity and temperature dependence are key rheological concepts. Suspensions are multi-phase liquid dosage forms where particles are dispersed in a vehicle. Stabilizing suspensions requires controlling sedimentation, viscosity and rheology. Various excipients like thickeners, buffers, and preservatives are used to improve stability.
This document discusses preformulation for new drug development. A change in formulation, dosage, route of administration, or dosage form of an existing drug causes it to be considered "new" and requires safety and efficacy evaluation. Preformulation aims to optimize a drug's physical and chemical properties for a stable, effective dosage form. It involves characterizing the drug molecule and developing the dosage form. Some goals of preformulation include establishing the drug's physicochemical parameters, kinetic profile, physical characteristics, and compatibility with excipients. Polymorphism, or the ability of a drug to exist in different crystal forms, is also evaluated as it can impact properties like solubility, dissolution rate, and bioavailability.
Solid dispersion is an effective way of improving the dissolution rate of poorly water soluble drugs and hence its bioavailability. The water soluble carriers used in preparation of solid dispersion enhance the dissolution rate of the poorly water soluble drug. This work reflects the improvement of Dissolution Characteristics as well as Bioavailability of poorly aqueous soluble drug Hydrochlorothiazide. It belongs to BCS class 2 i.e. it has poor water solubility but good permeability.
Effect of hydrophilic polymers on solubility of some antihypertentives drugs ...SriramNagarajan19
The main aim of the present study is to carried out to enhance solubility of Felodipine. Felodipine.was selected as model drug and different carriers like Vitamin-E, Polyethylene Glycol 8000, Polyvinyl pyrrolidone K-30 were used in drug to carrier ratio 1:1, 1:2, 1:4 by weight respectively. Solid dispersions were prepared by physical mixing method and solvent evaporation method. Solid dispersions were evaluated by drug content, in-vitro release, FT-IR, DSC and XRD. The obtained data of solid dispersion prepared by solvent evaporation method were compared with physical mixing method. The result showed decrease in melting point change from crystalline to amorphous form and improved dissolution rate as compared to physical mixing as well as pure Felodipine. The finding of present study proposes that solid dispersion approach is beneficial in enhancing solubility of drug and bioavailability as well.
FORMULATION AND EVALUATION OF GELATIN MICROSPHERES LOADED WITH FENOFIBRATEReshma Fathima .K
The document summarizes the formulation and evaluation of gelatin microspheres loaded with the drug Fenofibrate. Two microsphere formulations were developed using a coacervation and phase separation method. Formulation F2 showed 97% drug encapsulation efficiency and released the drug over 12 hours, indicating it was suitable for oral sustained release. Evaluation tests on the microspheres showed they were spherical in shape, had good flow properties, and released the drug in a controlled manner without any burst release. The microspheres could facilitate the design of hard gelatin capsules for improved patient compliance.
The document summarizes research conducted on chia seeds and their mucilage. Key findings include:
- Chia seeds are a source of soluble fiber and nutrients. Extraction of mucilage from seeds yields 20-25%.
- Studies showed chia mucilage rapidly hydrates and swells in water. It exhibits pseudoplastic rheological behavior useful for emulsions and suspensions.
- Characterization found chia mucilage is a carbohydrate containing hydroxyl groups. It effectively suspended paracetamol in a paediatric formulation over 5 days without sedimentation.
Formulation and Evaluation of Pantoprazole Sodium Enteric Coated TabletsSriramNagarajan18
The document summarizes the formulation and evaluation of pantoprazole sodium enteric coated tablets. Pantoprazole is an acid-labile drug that requires enteric coating to protect it from degradation in the stomach. Various enteric coated tablet formulations were prepared using different concentrations of superdisintegrants and enteric coating polymers. Tablets were evaluated for hardness, thickness, weight variation, friability, drug content and in vitro drug release. Formulation EC8, coated with 6% Eudragit RS100, showed the best results with a thickness of 2.2mm, hardness of 3.52kg/cm2, drug release of 100.16% within 2 hours and 45 minutes, and acid resistance
Formulation and in-vitro Evaluation of Disclofenac Microspheres for Sustained...Sunil Vadithya
This document outlines a study to develop diclofenac microspheres for sustained drug delivery. Microspheres were prepared using various polymers via an ionotropic gelation method and evaluated for yield, particle size, drug entrapment efficiency, and in vitro drug release. Five formulations were developed using sodium alginate, HPMC, ethylcellulose, or eudragit alone or in combination. The microspheres were characterized for surface morphology, yield between 79-88%, and showed potential for sustained release of diclofenac.
Preformulation involves characterizing the physicochemical properties of a drug prior to formulation development. Key aspects of preformulation studied include determining solubility, stability, and bulk properties of the drug substance. Analytical methods are also developed to quantitatively analyze the drug. This information guides the selection of appropriate excipients and dosage forms that will deliver the drug safely and effectively.
Mucilage of basil seed can be employed as a potential ingredient in suspensions, emulsions, gels and tablets especially as viscosity enhancing agents, thickening agent, emulsifier or gelling agent and release retardant because of its good hydrophilic nature, physical stability, barrier properties, efficient control of release profile, extrudability and good spreadability.
Extensive characterisation of natural polymer in dosage form development for subsequent commercialisation has given rise to a new term “Naturapolyceutics”.
Preparation, In Vitro and In Vivo Characterization of Solid Dispersions of La...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Formulation of Rutin trihydrate Liposomes for Topical Deliveryprescottasia
1. Rutin trihydrate liposomes were formulated using the thin film hydration method to enhance topical delivery of the antioxidant rutin trihydrate.
2. The liposomes were characterized for parameters like entrapment efficiency, vesicle size, and zeta potential. The optimized formulation showed 88% entrapment efficiency.
3. In vitro and ex vivo release studies showed that the rutin trihydrate liposomal gel provided prolonged drug release over 12 hours and exhibited anti-elastase activity, demonstrating its potential for topical delivery applications.
The document discusses a study on enhancing the solubility of loratadine, a class II drug with low solubility and high permeability, through solid dispersion techniques. Loratadine's solubility decreases with increasing pH. The study prepares solid dispersions of loratadine with β-cyclodextrin, HPC, and PEG-6000 and finds their solubility is greatly improved, especially at higher pH levels. Solubility is tested in buffers from pH 1.2 to 7.4. The co-precipitation method provides better solubility results than physical mixing for the dispersions tested.
folic acid chitosan conjugate nanoparticle containing azithromycin for the tr...shivamgupta1083
The document presents a research proposal for developing folic acid-chitosan conjugate nanoparticles containing azithromycin for treating colorectal diseases. The objectives are to prepare drug-loaded conjugates with desired release characteristics and assess their targeting efficacy and bio-distribution. The plan involves preformulation studies, preparing the folic acid-chitosan conjugate, loading the conjugate with azithromycin, and characterizing the nanoparticles. In vitro and in vivo studies will evaluate particle properties, drug release, cytotoxicity, and the ability to treat colorectal inflammation in a rat model.
This document presents the development of nizatidine mucoadhesive microballoons for the treatment of peptic ulcers. Peptic ulcers occur in the stomach and duodenum due to an imbalance between aggressive and defensive factors. Nizatidine is an H2 receptor antagonist used to treat peptic ulcers. The objective is to develop microballoons to increase gastric residence time and bioavailability of nizatidine. Preformulation studies including solubility, compatibility and analytical method development were conducted. Microballoons will be formulated using different polymer combinations and evaluated for properties like mucoadhesion, drug release and stability. The formulation aims to localize delivery and prolong drug release for better management of
Application of preformulation consideration in the development ofArpan Dhungel
This document discusses preformulation studies for developing parenteral dosage forms. Preformulation involves studying a new drug's physicochemical properties to create stable, effective formulations. Key aspects of preformulation include assessing solubility through methods like changing pH, adding co-solvents or complexing agents, and evaluating stability under various conditions like heat, light and pH to determine a drug's degradation profile. The goal of preformulation is to obtain information to guide formulation development and ensure the drug molecule is most stable.
This document summarizes a study that used the liquisolid technique to enhance the dissolution rate of the poorly water soluble drug ketoprofen. Several liquisolid tablet formulations were prepared using ketoprofen as the drug and propylene glycol or tween 80 as liquid vehicles. Microcrystalline cellulose and dicalcium phosphate were used as carriers and silica gel as the coating material. The liquisolid tablets showed improved flow properties and higher drug release compared to marketed ketoprofen tablets. X-ray diffraction and FTIR analysis indicated no drug-excipient interactions. The liquisolid technique was effective in enhancing the dissolution of the poorly soluble drug ketoprofen.
This document provides an overview of preformulation studies for semisolid dosage forms. It begins with defining preformulation as the investigation of a drug substance's physical and chemical properties alone and when combined with excipients. The objectives of preformulation are to develop a safe, effective, stable pharmaceutical dosage form and to understand a drug's properties before formulation development. Key physicochemical parameters discussed include penetration, solubility, texture analysis, effect of light, salt formation, degradation pathways, partition coefficient, and hygroscopicity. The document concludes that preformulation is an important first step in rational dosage form development.
Cubosomal nanoparticles as an ocular delivery system of fluconazoleSidharth Mehta
The optimized cubosomal dispersion exhibited spherical nanosized particles and reasonable EE% along with higher
FCZ corneal permeation (twofold) as compared to that of FCZ solution.
Moreover, the in vivo study proved the efficacy and safety FCZ-loaded
cubosomal dispersion in treatment of induced keratomycosis
in rats compared to aqueous FCZ solution after topical ocular
application.
Based on the previous results, the use of
cubosomal dispersion as an ocular drug delivery system is
expected to improve antifungal activity of FCZ in treatment
of fungal keratitis.
This document summarizes a study on enhancing the dissolution rate of olanzapine, an antipsychotic drug with poor water solubility, using solid dispersion techniques. The study aimed to prepare solid dispersions of olanzapine with various carriers using physical mixture, solvent evaporation, and kneading methods. Dissolution tests found that the solid dispersions significantly increased the dissolution rate of olanzapine compared to the raw drug. Carriers like PEG 4000, PEG 6000, and HP-βCD were most effective at enhancing dissolution when prepared by the kneading or solvent evaporation methods. FT-IR analysis was used to evaluate drug-carrier interactions. The results of this study demonstrate that solid dispersion is an
This document discusses the importance of rheology in developing pharmaceutical formulations. Rheology considers how materials deform under stress, which directly impacts how drugs are formulated and how patients use medications. Viscosity and temperature dependence are key rheological concepts. Suspensions are multi-phase liquid dosage forms where particles are dispersed in a vehicle. Stabilizing suspensions requires controlling sedimentation, viscosity and rheology. Various excipients like thickeners, buffers, and preservatives are used to improve stability.
This document discusses preformulation for new drug development. A change in formulation, dosage, route of administration, or dosage form of an existing drug causes it to be considered "new" and requires safety and efficacy evaluation. Preformulation aims to optimize a drug's physical and chemical properties for a stable, effective dosage form. It involves characterizing the drug molecule and developing the dosage form. Some goals of preformulation include establishing the drug's physicochemical parameters, kinetic profile, physical characteristics, and compatibility with excipients. Polymorphism, or the ability of a drug to exist in different crystal forms, is also evaluated as it can impact properties like solubility, dissolution rate, and bioavailability.
Solid dispersion is an effective way of improving the dissolution rate of poorly water soluble drugs and hence its bioavailability. The water soluble carriers used in preparation of solid dispersion enhance the dissolution rate of the poorly water soluble drug. This work reflects the improvement of Dissolution Characteristics as well as Bioavailability of poorly aqueous soluble drug Hydrochlorothiazide. It belongs to BCS class 2 i.e. it has poor water solubility but good permeability.
Effect of hydrophilic polymers on solubility of some antihypertentives drugs ...SriramNagarajan19
The main aim of the present study is to carried out to enhance solubility of Felodipine. Felodipine.was selected as model drug and different carriers like Vitamin-E, Polyethylene Glycol 8000, Polyvinyl pyrrolidone K-30 were used in drug to carrier ratio 1:1, 1:2, 1:4 by weight respectively. Solid dispersions were prepared by physical mixing method and solvent evaporation method. Solid dispersions were evaluated by drug content, in-vitro release, FT-IR, DSC and XRD. The obtained data of solid dispersion prepared by solvent evaporation method were compared with physical mixing method. The result showed decrease in melting point change from crystalline to amorphous form and improved dissolution rate as compared to physical mixing as well as pure Felodipine. The finding of present study proposes that solid dispersion approach is beneficial in enhancing solubility of drug and bioavailability as well.
FORMULATION AND EVALUATION OF GELATIN MICROSPHERES LOADED WITH FENOFIBRATEReshma Fathima .K
The document summarizes the formulation and evaluation of gelatin microspheres loaded with the drug Fenofibrate. Two microsphere formulations were developed using a coacervation and phase separation method. Formulation F2 showed 97% drug encapsulation efficiency and released the drug over 12 hours, indicating it was suitable for oral sustained release. Evaluation tests on the microspheres showed they were spherical in shape, had good flow properties, and released the drug in a controlled manner without any burst release. The microspheres could facilitate the design of hard gelatin capsules for improved patient compliance.
The document summarizes research conducted on chia seeds and their mucilage. Key findings include:
- Chia seeds are a source of soluble fiber and nutrients. Extraction of mucilage from seeds yields 20-25%.
- Studies showed chia mucilage rapidly hydrates and swells in water. It exhibits pseudoplastic rheological behavior useful for emulsions and suspensions.
- Characterization found chia mucilage is a carbohydrate containing hydroxyl groups. It effectively suspended paracetamol in a paediatric formulation over 5 days without sedimentation.
Formulation and Evaluation of Pantoprazole Sodium Enteric Coated TabletsSriramNagarajan18
The document summarizes the formulation and evaluation of pantoprazole sodium enteric coated tablets. Pantoprazole is an acid-labile drug that requires enteric coating to protect it from degradation in the stomach. Various enteric coated tablet formulations were prepared using different concentrations of superdisintegrants and enteric coating polymers. Tablets were evaluated for hardness, thickness, weight variation, friability, drug content and in vitro drug release. Formulation EC8, coated with 6% Eudragit RS100, showed the best results with a thickness of 2.2mm, hardness of 3.52kg/cm2, drug release of 100.16% within 2 hours and 45 minutes, and acid resistance
Formulation and in-vitro Evaluation of Disclofenac Microspheres for Sustained...Sunil Vadithya
This document outlines a study to develop diclofenac microspheres for sustained drug delivery. Microspheres were prepared using various polymers via an ionotropic gelation method and evaluated for yield, particle size, drug entrapment efficiency, and in vitro drug release. Five formulations were developed using sodium alginate, HPMC, ethylcellulose, or eudragit alone or in combination. The microspheres were characterized for surface morphology, yield between 79-88%, and showed potential for sustained release of diclofenac.
Preformulation involves characterizing the physicochemical properties of a drug prior to formulation development. Key aspects of preformulation studied include determining solubility, stability, and bulk properties of the drug substance. Analytical methods are also developed to quantitatively analyze the drug. This information guides the selection of appropriate excipients and dosage forms that will deliver the drug safely and effectively.
Mucilage of basil seed can be employed as a potential ingredient in suspensions, emulsions, gels and tablets especially as viscosity enhancing agents, thickening agent, emulsifier or gelling agent and release retardant because of its good hydrophilic nature, physical stability, barrier properties, efficient control of release profile, extrudability and good spreadability.
Extensive characterisation of natural polymer in dosage form development for subsequent commercialisation has given rise to a new term “Naturapolyceutics”.
Preparation, In Vitro and In Vivo Characterization of Solid Dispersions of La...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Formulation of Rutin trihydrate Liposomes for Topical Deliveryprescottasia
1. Rutin trihydrate liposomes were formulated using the thin film hydration method to enhance topical delivery of the antioxidant rutin trihydrate.
2. The liposomes were characterized for parameters like entrapment efficiency, vesicle size, and zeta potential. The optimized formulation showed 88% entrapment efficiency.
3. In vitro and ex vivo release studies showed that the rutin trihydrate liposomal gel provided prolonged drug release over 12 hours and exhibited anti-elastase activity, demonstrating its potential for topical delivery applications.
The document discusses a study on enhancing the solubility of loratadine, a class II drug with low solubility and high permeability, through solid dispersion techniques. Loratadine's solubility decreases with increasing pH. The study prepares solid dispersions of loratadine with β-cyclodextrin, HPC, and PEG-6000 and finds their solubility is greatly improved, especially at higher pH levels. Solubility is tested in buffers from pH 1.2 to 7.4. The co-precipitation method provides better solubility results than physical mixing for the dispersions tested.
folic acid chitosan conjugate nanoparticle containing azithromycin for the tr...shivamgupta1083
The document presents a research proposal for developing folic acid-chitosan conjugate nanoparticles containing azithromycin for treating colorectal diseases. The objectives are to prepare drug-loaded conjugates with desired release characteristics and assess their targeting efficacy and bio-distribution. The plan involves preformulation studies, preparing the folic acid-chitosan conjugate, loading the conjugate with azithromycin, and characterizing the nanoparticles. In vitro and in vivo studies will evaluate particle properties, drug release, cytotoxicity, and the ability to treat colorectal inflammation in a rat model.
This document presents the development of nizatidine mucoadhesive microballoons for the treatment of peptic ulcers. Peptic ulcers occur in the stomach and duodenum due to an imbalance between aggressive and defensive factors. Nizatidine is an H2 receptor antagonist used to treat peptic ulcers. The objective is to develop microballoons to increase gastric residence time and bioavailability of nizatidine. Preformulation studies including solubility, compatibility and analytical method development were conducted. Microballoons will be formulated using different polymer combinations and evaluated for properties like mucoadhesion, drug release and stability. The formulation aims to localize delivery and prolong drug release for better management of
This document presents the development of nizatidine mucoadhesive microballoons for the treatment of peptic ulcers. Peptic ulcers occur in the stomach and duodenum due to an imbalance between aggressive and defensive factors. Nizatidine is an H2 receptor antagonist used to treat peptic ulcers. The objective is to develop microballoons to increase gastric residence time and bioavailability of nizatidine. Preformulation studies including solubility, compatibility and analytical method development were conducted. Microballoons will be formulated using different polymer combinations and evaluated for properties like mucoadhesion, drug release and stability. The formulation aims to localize nizatidine delivery and maintain therapeutic drug
Design, Development, Evaluation and Optimization of Microballoons of TelmisartanSnehal Patel
Abstract: In present study an attempt was made to prepare microballoons of
Telmisartan by emulsion solvent diffusion technique for sustained delivery by
using polymers like Ethyl cellulose to extend the drug release for about 12 hours in
the upper GIT, which may result in enhanced absorption and there by improved
bioavailability. Formulation optimization of Telmisartan loaded microballoons was
carried out by using different concentration of Polyvinyl alcohol (PVA) and Ethyl
cellulose. Total 9 batches were formulated. All 9 batches were evaluated for
entrapment efficiency (EE) and buoyancy. Among all batches DP4 shows
maximum entrapment efficiency (EE) and buoyancy and was considered as
optimized formulation. DP4 batch was further used for process optimization. The
process optimization was carried out at three different stirring speeds i.e. 1300,
1500 and 1700 rpm for three different stirring time period i.e. 1hr, 2hr and 3 hr and
another 9 batches were formulated. Out of all the batches DP13 showed the
spherical shape of microballoons without formation of flakes. Optimized batch
DP13 was evaluated for Zeta Potential, Particle Size Distribution which show -
41.8mV and 1.344 μm particle size, SEM, XRD Analysis. Batch DP13 was
charged for stability and were placed in glass vials container and stored at ICH
storage condition (2°C - 4°C Refrigeration condition , 30 ± 2°C / 60% ± 5% RH ,
40 ± 2°C / 75% ± 5% RH ) for a period of 30 days. The samples were analyzed for
physical appearance, buoyancy and for the drug release after 30 days. After 1
months samples were withdrawn and microballoons showed no change in physical
appearances, buoyancy and drug release, which indicate that the microballoons
were stable.
Keywords: Telmisartan, Microballoons, Emulsion solvent diffusion technique,
Buoyancy, Entrapment Efficiency.
Development and in vitro evaluation of polyphenols (catechin) loaded mucoadhe...SriramNagarajan17
This document describes the development and in vitro evaluation of mucoadhesive buccal patches containing the polyphenol catechin. Various formulations were prepared using different polymers like HPMC, CMC, and chitosan, as well as an extract from Vinga radiata. The best performing formulation in terms of mucoadhesive properties and in vitro drug release was one containing a 1:1.5 ratio of chitosan and Vinga radiata extract. This formulation showed less erosion, faster hydration, an optimal pH, and released 66.2% of the drug within 6 hours in diffusion studies. Stability testing found it retained over 97% of the drug content after one month of storage.
Effervescent technique in development of floating tablets for antiviral drugsSriramNagarajan19
The purpose of this investigation was to prepare a regiospesific drug delivery system of Stavudine. Floating tablets of Stavudine were prepared by direct compression method employing different concentration of HPMC K15M by effervescent technique. Sodium bicarbonate was incorporated as a gas-generating agent. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, swelling studies, in vitro buoyancy and dissolution studies. The effect of different concentration of HPMC K15M on drug release profile and floating properties was investigated. The prepared tablets exhibited satisfactory physico-chemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for more than 12 hours. Increased in the HPMC K15M level, decreased the floating lag time but tablets floated for longer duration. The formulation with 1:1 drug: Polymer ratios were found to float for longer duration as compared with other formulations containing HPMC K15M. The drug release from the tablets was sufficiently sustained and non-Fickian transport of the drug from tablets was confirmed.
FORMULATION AND INVITRO EVALUATION OF COLON SPECIFIC DRUG DELIVERY SYSTEM BY ...alok prakash kar
The document describes the formulation and in vitro evaluation of a colon-specific drug delivery system containing metronidazole. Metronidazole tablets were prepared using different polymers like ethyl cellulose, cellulose acetate butyrate, and Eudragit polymers. The tablets were then coated with various polymer coating suspensions. The coated tablets were evaluated for film thickness, weight gain, hardness, disintegration time, and drug release. The results showed that the coating thickness and weight gain increased with increasing polymer concentration in the coating suspension. The coated tablets had suitable hardness and disintegration times while sustaining drug release in the acidic environment of the stomach.
Formulation and Evaluation of Moxifloxacin Loaded Alginate Chitosan Nanoparti...pharmaindexing
This document describes the formulation and evaluation of moxifloxacin-loaded alginate-chitosan nanoparticles for treating tuberculosis. Moxifloxacin nanoparticles were prepared using an ionic gelation method with varying polymer ratios and drug concentrations. Formulation MF3, with a drug concentration of 50 mg, exhibited the highest encapsulation efficiency, drug loading, and rate of recovery. In vitro drug release from MF3 was sustained over 96 hours with no significant changes observed after 3 months of stability testing. Scanning electron microscopy confirmed the nanoparticles had a discrete spherical structure without aggregation.
Spectrophotometric Oxidation Method for the Determination of Teneligliptin by...ijtsrd
A sensitive, precise, accurate, simple and rapid spectrophotometric method has been developed for the estimation of Teneligliptin in pharmaceutical formulations and in the drug dosage form. During the course of study, it is observed that acidic solution of the drug formed the oxidation product with Bromate "“ Bromide mixture. This property of the drug is exploited for the development of spectrophotometric method for the determination and analysis of the drug. The oxidation product showed ?max at 250 nm. The linearity range for Teneligliptin is found to be 10 µgml to 250 µgml. Recovery studies gave satisfactory results indicating that none of common additives and excipients interfere the assay method. The molar absorptivity and the sandell sensitivity of the method are evaluated and the values are found to be to be 1.1645×104 lit molecm and 0.0366 µg mlcm2 respectively. I. Lakshmi Prasanna | G. T. Naidu | G. Abdul Huq"Spectrophotometric Oxidation Method for the Determination of Teneligliptin by Using Bromate "“ Bromide Mixture" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-2 | Issue-5 , August 2018, URL: http://www.ijtsrd.com/papers/ijtsrd18253.pdf http://www.ijtsrd.com/physics/other/18253/spectrophotometric-oxidation-method-for-the-determination-of-teneligliptin-by-using-bromate---bromide-mixture/i-lakshmi-prasanna
Formulation and Evaluation of Sublingual Tablets of Asenapine Maleate By 32 F...PRASANTAKUMARMOHAPAT3
Objectives: The aim of this work was to formulate and evaluate sublingual tablets of Asenapine
maleate for the treatment of schizophrenia and the treatment of manic episodes associated with
bipolar I disorder. Methods: In the present work, the bitter taste of Asenapine maleate was
masked by using Kyron T-114 in 1:1.5 ratio. The Drug-Resin Complex was formulated as
sublingual tablets using Cross Povidone (X1) and Avicel PH102 (X2) by direct compression
method. The sublingual tablets were evaluated such as thickness, hardness, % Friability,
Wetting time, disintegration time, Water absorption ratio and % CDR.Results: In this study, the
fast release of tablets depends on the concentration of Cross Povidone (X1) and Avicel PH102
(X2). The selected formulation showed the fastest release of the tablets in 54 s. Stability study
was performed by taking an optimized formulation and it was observed stable. The sublingual
tablets showed acceptable results in all studies.Conclusion: The results indicate that the
formulation can be used for the treatment of schizophrenia and the treatment of manic episodes
associated with bipolar I disorder. Moreover, Asenapine maleate as sublingual tablets may
overcome the first pass effect, gives better bioavailability, rapid onset of action and patient
compliance.
This document summarizes a study that developed and optimized chitosan-alginate nanoparticles for oral delivery of the drug rosuvastatin calcium. The nanoparticles were prepared using ionotropic gelation and characterized for properties such as size, surface charge, drug loading efficiency, and in vitro drug release. The optimized nanoparticles had an average size of 349.3 nm, a zeta potential of +29.1 mV, high drug loading and entrapment efficiencies, and showed a fast initial release followed by more gradual release over 24 hours. The study demonstrated that the chitosan-alginate nanoparticle system improved rosuvastatin solubility and has potential to enhance its oral bioavailability and therapeutic efficacy.
Formulation Development and Characterization of Topical Gel for PsoriasisBRNSS Publication Hub
The purpose of this research work was to develop and characterize a tacrolimus (TAC) gel using different
polymers for the treatment of psoriasis. The physicochemical compatibility was confirmed between
TAC and other excipients by Fourier transfer infrared. Formulated gels were characterized for drug
content, viscosity, extrudability, skin irritation study, pH, in vitro diffusion study, and stability. Release
of TAC from all formulations using dialysis membrane into a phosphate buffer pH 6.8 at 37°C was
performed. Optimized batch was selected from this characterization study. Based on the data collected,
it was revealed that TAC has proven to be a promising candidate for delivery through gel in the treatment
of psoriasis.
This document summarizes research on developing a sustained release microencapsulated delivery system for the drug famotidine using a combination of mucoadhesive polymers. Famotidine microcapsules were prepared using an orifice ionic gelation technique with various polymer combinations, including carbopol-934 with hydroxypropyl methylcellulose, sodium carboxymethylcellulose, methylcellulose, or guar gum. The microcapsules were evaluated for properties like particle size, yield, drug entrapment efficiency, surface morphology, swelling properties, in vitro drug release, and mucoadhesion. The results showed that microcapsules prepared with sustained release polymers in combination exhibited slow release of famotidine over 9 hours with zero
This document describes research into the microbial synthesis of platinum nanoparticles using Saccharomyces boulardii and evaluation of the anticancer activity of the synthesized platinum nanoparticles. Key findings include:
1) Platinum nanoparticles were successfully synthesized using the cell free extract of S. boulardii when reacted with chloroplatinic acid.
2) Various parameters like metal salt concentration, temperature, cellmass concentration, pH, and reaction time were optimized to control the yield and properties of the synthesized nanoparticles.
3) The synthesized platinum nanoparticles showed anticancer activity against A431 and MCF-7 cell lines with IC50 values between 57-100 μg/ml, indicating potential for use as an antic
Formulation and invivo evaluation of mucoadhesive microspheres embedded clero...SriramNagarajan19
In this study an attempt was made to prepare mucoadhesive microcapsules of Clerodendrum phlomidis extract using alginate polymers for prolonged release. Encapsulation of extract into sodium alginate polymer was done by ionic-gelation technique. In vivo testing of the mucoadhesive microcapsules in diabetic albino rats demonstrated significant antidiabetic effect of extract. The hypoglycemic effect obtained by mucoadhesive microcapsules was for more than 16 h whereas plain CP extract produced an antidiabetic effect for only 4 h suggesting that mucoadhesive microcapsules are a valuable system for the long term delivery of CP extract. In-vivo data obtained over a 120-h period indicate that CP extract loaded alginate microspheres from batch F7 showed the better glycemic control than control and a commercial brand of the drug.
A poloxamer /chitosan in situ forming gel with prolonged retention time for o...veeranna-bhukya
The document summarizes research on developing an in-situ forming ocular gel made of poloxamer and chitosan polymers for prolonged drug retention time. Key points:
- A poloxamer/chitosan gel was formulated to be liquid at instillation and undergo sol-gel transition in the eye cul-de-sac. Rheological tests showed the gel had elastic properties at ocular surface temperature.
- In vitro tests found the gel had appropriate gelation temperature and increased mechanical strength and mucoadhesion over poloxamer alone.
- In vivo scintigraphy on human volunteers showed the gel remained in contact with the cornea longer (65% at 2 min) than saline control
In vitro and in vivo evaluation of positively charged liposaccharide derivati...Adel Abdelrahim, PhD
This document describes a study evaluating positively charged liposaccharide derivatives as oral absorption enhancers for delivering anionic drugs. Positively charged liposaccharide derivatives were synthesized and combined with the anionic model drug piperacillin through ion pairing. The conjugates were evaluated in vitro and in vivo to assess antimicrobial activity, plasma stability, permeability across Caco-2 cell monolayers, and oral absorption. Results showed that ion pairing the liposaccharide derivatives with piperacillin improved permeability in Caco-2 cells without altering antimicrobial activity, indicating potential as oral absorption enhancers.
Royal jelly accelerates recovery from oral mucositisBee Healthy Farms
Great news for cancer patients who suffer from oral mucositis. However, individuals undergoing this type of intense therapy also need to consume large quantities of propolis to protect their weakened immune system.
Mucoadhesive microcapsules of rifampicin were prepared using sodium alginate, sodium carboxymethyl cellulose, and chitosan polymers to provide controlled release of the drug. Microcapsules were discrete and spherical with sizes ranging from 780-882nm. Encapsulation efficiency was 75-88%. In vitro drug release studies showed release was sustained over longer periods, from 26-46 hours depending on the polymer ratio, and followed zero-order kinetics. Formulation F11 using a 1:2:2 ratio of sodium alginate and chitosan provided the longest release time of 46 hours, making it suitable for an oral controlled release product.
Preparation and Evaluation of Dermal Patch Containing Calendula Officinalis f...Suraj Mohan
The document describes the development and evaluation of dermal patches containing Calendula Officinalis for antimicrobial activity. Five formulations of dermal patches with varying drug content were prepared using HPMC and SCMC as polymers and polyethylene glycol as a plasticizer. The patches were evaluated for thickness, weight uniformity, folding endurance and moisture content. Scanning electron microscopy showed the patches had an irregular, rough surface which could aid in drug release. The patches were also tested for antimicrobial activity against Staphylococcus aureus using the disc diffusion method.
Similar to The effect of conjugation on different polymers in bioadhesive films of losartan (20)
Stability indicating method and validation for the simultaneous estimation of...SriramNagarajan18
Stability indicating method and validation for the simultaneous estimation of metformin and empagliflozin by using RP-HPLC in a bulk and pharmaceutical dosage forms
Carnilitye capsule; Enhances body's ability to convert fat into energySriramNagarajan18
This document summarizes research on L-carnitine and its effects on athletic performance and energy production. It finds that L-carnitine transports fatty acids to mitochondria to be burned for energy, helps spare glycogen stores, and may improve lactate clearance and blood flow. Supplementing with L-carnitine was shown to increase fatty acid utilization, aerobic power, and exercise performance while decreasing fatigue. The document also reviews the suggested benefits and safety of L-carnitine supplementation for athletes and others needing increased energy production.
Synthesis and characterization of new benzotriazole derivatives for possible ...SriramNagarajan18
This document describes the synthesis and characterization of new benzotriazole derivatives (Va-Vg) for potential central nervous system (CNS) activity. The derivatives were synthesized in multiple steps starting from O-phenylenediamene. The intermediates and final compounds were characterized using techniques like IR, 1H NMR, mass spectrometry and elemental analysis. All compounds were screened for CNS activity through gross behavioral studies and locomotor activity tests. Compound Vb containing a 4-chloro substitution showed the most promising depressant activity among the test compounds, followed by Vg and Ve.
Stability indicating method development and validation for the estimation of ...SriramNagarajan18
Stability indicating method development and validation for the estimation of Doxorubicin by using RP-HPLC method in a bulk and pharmaceutical dosage form
LACTOWHEY powder: Provides body’s defense against cancerSriramNagarajan18
Lactowhey powder is a whey protein supplement that provides several potential health benefits. It contains amino acids that help stimulate immunity and increase glutathione levels, which enhances the body's defense against cancer, free radicals, and carcinogens. Pre-clinical and clinical studies have shown that Lactowhey powder may help prevent muscle loss and weight loss in cancer patients by improving nutritional status and appetite. The whey proteins and other components in Lactowhey powder are easily absorbed and can promote muscle strength and immune function.
FORMULATION AND EVALUATION OF GEL LOADED MICROSPONGES OF DICLOFENAC SODIUM FO...SriramNagarajan18
This document describes the formulation and evaluation of diclofenac sodium-loaded microsponges for topical delivery. Microsponges were prepared using ethyl cellulose polymer by a quasi-emulsion solvent diffusion method. The microsponges were spherical and porous in structure as seen under SEM. Particle size ranged from 23.9-45.9 μm depending on the drug:polymer ratio. Yield increased from 10.85-41.03% with increasing polymer content. Drug content was highest for formulation M4 at 74.03% and decreased with higher polymer ratios. The microsponges were then dispersed in a carbopol gel and evaluated for properties like pH, viscosity and spreadability. In vitro drug
Formulation and In vitro evaluation of Fosinopril fast dissolving tabletsSriramNagarajan18
This document summarizes a study that formulated and evaluated fast dissolving tablets containing the drug fosinopril. Nine formulations of fosinopril tablets were prepared using different concentrations of superdisintegrants like croscarmellose sodium (CCS), crospovidone (CP), and sodium starch glycolate (SSG). The tablets were evaluated for pre-compression and post-compression parameters. In vitro drug release studies found that formulation F7, containing 20% SSG, showed maximum drug release within 30 minutes. Fourier transform infrared spectroscopy confirmed no drug-excipient interactions. The study developed fast dissolving fosinopril tablets using superdisintegrants and evaluated their characteristics.
Formulation and evaluation of rapimelts of EletriptanSriramNagarajan18
This document describes the formulation and evaluation of rapid-melting tablets containing the drug Eletriptan. Twelve formulations were created using different superdisintegrants like crospovidone, cros carmellose sodium, and sodium starch glycolate. The tablets were prepared by direct compression method and evaluated for properties like hardness, thickness, friability, drug content and in-vitro drug release. Formulation F3 with 10% crospovidone showed maximum drug release of 99.9% within 6 minutes and was selected as the optimized formulation based on rapid disintegration time of 16.33 seconds and high drug release. Fourier transform infrared spectroscopy confirmed no drug-excipient interactions in the optimized formulation.
Design, development and evaluation of Itraconazole loaded transfersomal gelSriramNagarajan18
This document describes the design, development, and evaluation of an itraconazole-loaded transfersomal gel for transdermal drug delivery. Transfersomes are deformable lipid vesicles that can improve skin permeation of drugs. The researchers prepared various transfersome formulations containing itraconazole, lecithin, and different ratios of surfactants (Span 80 and Tween 80). They characterized the transfersomes for vesicle shape, size, drug entrapment efficiency, and in vitro permeation. Transfersomal gel was then prepared by dispersing the optimized transfersome formulation in carbopol gel. Evaluation showed the transfersomal gel was a promising candidate for transdermal delivery of itraconazole with
Formulation and evaluation of tramadol using pulsincap technologySriramNagarajan18
This document describes the formulation and evaluation of tramadol pulsincaps using pulsincap technology for colon-specific delivery. Tramadol granules were prepared by blending the drug with polymers like HPMC K4M and ethyl cellulose. Hard gelatin capsules were treated with formaldehyde to make them insoluble in the stomach and small intestine. The granules were filled into the treated capsule bodies and sealed with a hydrogel plug. The formulations were evaluated for flow properties, drug content, and in vitro dissolution. Dissolution studies showed the formulations released drug in a pulsatile manner with a lag time followed by rapid release. Formulation F3 with 30% polymer showed the highest drug release of 96
An overview on Gastroretentive drug delivery systemsSriramNagarajan18
This document provides an overview of gastroretentive drug delivery systems (GRDDS). It discusses how GRDDS are designed to prolong the gastric retention time of orally administered drugs to improve their bioavailability. The document describes various approaches for GRDDS, including floating systems that float in the stomach, high density systems that sink to the bottom of the stomach, bioadhesive systems that adhere to the stomach lining, and unfoldable systems that expand in the stomach. It also discusses factors that influence gastric retention and the advantages of GRDDS for drugs that need to remain in the stomach.
Formulation and In Vitro characterization of transdermal patches of EtodolacSriramNagarajan18
This document summarizes the formulation and characterization of transdermal patches containing etodolac. Etodolac patches were prepared using different polymers like HPMC and EC alone and in combinations. The patches were evaluated for thickness, drug content, in vitro permeation, and kinetic studies. The patch containing HPMC E5 and EC in a 5:5 ratio (F7) showed the maximum drug release of 87.825% within 24 hours. The results suggest that etodolac transdermal patches can be successfully formulated using various ratios of EC and HPMC E5 polymers.
The Left atrial appendage closure - A watchman deviceSriramNagarajan18
The document summarizes the left atrial appendage closure device called the Watchman. It is used as an alternative to oral anticoagulation drugs for preventing stroke in atrial fibrillation patients. The Watchman device is implanted via catheter into the left atrial appendage to block blood clots from forming there and causing strokes. The document describes the implantation procedure and compares the Watchman device to another left atrial appendage closure device. It concludes that the Watchman device appears safe and effective for reducing stroke risk in atrial fibrillation patients who cannot safely take oral anticoagulants.
Phytochemical screening and estimation of sun protection factor from fruits a...SriramNagarajan18
This document discusses a study that performed phytochemical screening and determined the sun protection factor (SPF) of ethanolic extracts from various fruits and plants, including cucumis sativus, carica papaya, citrus sinensis, and solanum lycoperisum. The study found that all of the ethanolic extracts showed some UV protection capability. Phytochemical screening revealed the presence of various compounds including alkaloids, carbohydrates, glycosides, tannins, phytosterols, and flavonoids in the different plant extracts. The SPF of each extract was determined using spectrophotometry to measure absorbances between 290-320 nm according to international methods.
Formulation and evaluation of ciclopirox using ethosomal gelSriramNagarajan18
This document summarizes a study that formulated and evaluated a ciclopirox ethosomal gel for transdermal drug delivery. Twelve ethosomal formulations were prepared with varying concentrations of phospholipids (2-4% w/v) and ethanol (20-50% w/v). Formulation EF7, containing 3% lecithin and 40% ethanol, was optimized based on drug release kinetics and characterized for particle size. The optimized ethosomes were incorporated into a gel base and the ethosomal gel was evaluated for various properties like physical appearance, pH, drug content uniformity, rheological behavior and in-vitro drug release. Results showed that ethosomal formulations were able to deliver ciclopi
Development and Evaluation of gastroretentive matrix tablets of NateglinideSriramNagarajan18
This document summarizes research on developing and evaluating gastroretentive matrix tablets containing nateglinide, an oral drug used to treat diabetes. Nine floating tablet formulations were created using different polymers (xanthan gum, HPMC, carbopol) in various ratios. Tablets were evaluated for properties like drug release kinetics, buoyancy, and hardness. Formulation F4 containing HPMC K100M showed the best controlled drug release and floating properties over 12 hours. Drug release from F4 best fit the Korsmeyer-Peppas and Higuchi models, indicating non-Fickian (anomalous) diffusion. The polymers were effective at prolonging the release of nateglinide from the floating tablets to increase
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.
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.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
The effect of conjugation on different polymers in bioadhesive films of losartan
1. Ravuri Sandeep et al / Int. J. of Farmacia, 2017; Vol-(3) 1: 25-43
25
International Journal of Farmacia
Journal Home page: www.ijfjournal.com
The effect of conjugation on different polymers in bioadhesive films of
losartan
Ravuri Sandeep*
, Sivakumar S
National College of Pharmacy, Department of Pharmaceutics, Shimoga - 577 201 Karnataka,
India
Corresponding Author: Ravuri Sandeep
*
E-mail: ravuri_sandeep@yahoo.co.in
ABSTRACT
The objective of the present study was to develop mucoadhesive buccal films of losartan potassium using sodium
alginate, chitosan, and their conjugated derivatives at different concentrations by solvent casting technique. Glycerin
was used as plasticizer, at different weight ratios. The conjugation of polymers (sodium alginate-cysteine and
chitosan-thioglycolic acid) was confirmed by FTIR study. The resulted conjugated sodium alginate and chitosan
displayed 475.64±24.31 and 305±31.21 μmol thiol groups per g conjugate, respectively. The developed films were
evaluated by different parameters such as weight uniformity, thickness, surface pH, swelling index, in vitro
residence time, mucoadhesive strength, in vitro and ex vivo drug permeation. The results indicated that the
formulations S5, C4, Cs and Cc showed better characteristic properties and drug permeation. Good results were
obtained both in vitro and ex vivo conditions for optimized film. A higher glycerin percent in films increased the
drug permeation, particularly at a polymer concentration of 10 to 30% w/v (S2-S4 and C2-C4). A further increase of
glycerin (40 to 50% w/v) did not improve losartan potassium permeation (S6 and C6). Formulations Cs and Cc
containing conjugated sodium alginate and chitosan resulted in a significantly higher bioadhesion, swelling with
better drug permeation over long period than films comprising unmodified polymers. Stability studies on optimized
formulations indicated that the formulations are stable as no significant difference was observed in either drug
content or drug release.
Keywords: Buccal drug delivery, Sodium alginate–cysteine conjugate, Chitosan-thioglycolic acid conjugate,
Losartan potassium, Permeation study, Sustained release.
INTRODUCTION
Within the last decade, the concept of
mucoadhesive polymeric excipients has gained a new
dimension by introducing thiolated polymers at the
pharmaceutical arena. Thiolated polymers or
designated thiomers are new generation
mucoadhesive basis polymers, which display thiol
bearing side chains. Thiomers, represent a new class
of efficient mucoadhesive polymers with improved
mucoadhesive and permeation enhancing properties.
In this study thiolated chitosan and thiolated
sodium alginate was chosen as a polymeric drug
carrier. Only a few studies have so far been
performed on the usefulness of thiolated polymers as
drug delivery systems and no buccal applications has
been investigated for these films yet. Few researchers
have tried to deliver a drug systemically by using
thiolated polymers through the oral cavity including
peptide drug delivery [1], microparticles [2]. In the
present study, Losartan potassium was chosen as the
model drug. Losartan potassium is an orally active
angiotensin II receptor antagonist indicated for the
treatment of hypertension. [3] The conventional oral
dosage form of Losartan potassium undergoes
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26
substantial first pass metabolism and the systemic
bioavailability is only about 33%. Peak plasma
concentrations are achieved in 1 h. The
antihypertensive effect, measured at trough using
once daily dosing, is inadequate. A twice daily
regimen at the same daily dose, may give a more
satisfactory response. Twice daily regimen, however,
leads to patient incompliance, fluctuations in the drug
blood level and other adverse effects associated with
the conventional drug delivery system. [4] All these
properties, such as extensive hepatic first pass
metabolism (67%), short biological half-life (2 h), low
dose (25– 50 mg), low oral bioavailability (33%)
MATERIALS AND METHODS
All the materials obtained and used are of
analytical grade. Losartan potassium obtained from
Karnataka antibiotics Pvt Ltd., Bangalore. Sodium
alginate and Chitosan obtained from Sigma-Aldrich
chemicals Pvt Ltd., Mumbai. Carbodiimide
hydrochloride and Thiogycolic acid obtained from
Spectrochem Pvt Ltd., Mumbai. L-Cysteine Loba
obtained from Chemicals Pvt Ltd., Mumbai. Glycerin
obtained from S.D. Fine Chem. Pvt Ltd., Mumbai.
Dialysis membrane 110 obtained from Himedia
private Pvt Ltd., Mumbai
Methodology
Preparation of phosphate buffer pH 6.8
6.8 g of potassium dihydrogen phosphate was
dissolved in 250 ml of distilled water and this solution
was diluted to 1000 ml in a volumetric flask. To it 1.2
gm of NaOH in 112 ml distilled water was added.
Then the volume was made up to 1000 ml with
distilled water.
Calibration curve of losartan potassium in
phosphate buffer pH 6.8
Calibration curve of losartan potassium was
developed by suitably diluting the previously
prepared stock solution (1000 μg/ml) of drug using
phosphate buffer pH 6.8. Absorbance of serially
diluted (1-10 μg/ml) solutions were measured using a
UV-spectrophotometer (UV-1601, SHIMADZU,
Japan) at 227 nm against a suitable blank. A
calibration curve was plotted using Microsoft Excel
software.
Synthesis of conjugated polymers
Conjugation of polymer chitosan - thioglycolic
acid [5, 6]
500 mg of chitosan was hydrated in 4 ml of 1 M
HCl and dissolved by the addition of demineralized
water in order to obtain a 1 % w/v solution of chitosan
hydrochloride. Thereafter, EDAC was added in a final
concentration of 50 mM. After EDAC was completely
dissolved in the chitosan hydrochloride solution, 500
mg of TGA was added. The pH was adjusted to 4.0
using 1 M NaOH. The reaction mixture was incubated
for 3 h at room temperature. The resulting chitosan –
thioglycolic acid conjugate was isolated by dialyzing
at 10 ºC against 1mM HCl, followed by two times
against the same medium but also containing 1%
NaCl and then exhaustively against 1 mM HCl.
Thereafter, sample was stored in a desiccator under
vacuum until completely dried. The dried conjugated
chitosan was powdered using glass mortar-pastel and
passed through sieve number 60 and stored in
desiccator until further use.
Conjugation of polymer sodium alginate-L-
cysteine [7, 8]
1 gm of sodium alginate was dissolved in 100ml
demineralized water in order to obtain a 1 % w/v
polymer solution. Thereafter, EDAC was added in a
final concentration of 50 mM. After EDAC was
completely dissolved in the chitosan hydrochloride
solution, 500 mg of L- cysteine monohydrate
hydrochloride was added and the pH was adjusted to
4.0 with 1 M HCl. The reaction mixture was
incubated for 2 h under stirring at room temperature.
The pH was adjusted to 6.0 using 1 M NaOH. The
reaction mixture was incubated for 3 h at room
temperature under permanent stirring. The resulting
alginate–cysteine conjugate was isolated by dialyzing
at 10 ºC against 1mM HCl, followed by two times
against the same medium but also containing 1%
NaCl and then exhaustively against 1 mM HCl.
Thereafter, sample was dried in desiccator under
vacuum. The dried conjugated chitosan was powdered
and stored in desiccator until further use.
Confirmation of prepared polymer conjugates
FT-IR Spectrophotometric analysis
The sample of drug and drug-polymer mixture
were subjected to attenuated total refraction and
scanned from 4000 cm-1
to 500 cm-1
using FT-IR
spectrophotometer (Bruker-α-T, Germany)
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Determination of charring point
The charring point of the polymer conjugates were
determined by taking approximately 5 mg of the
sample in a glass capillary tube sealed at one end. The
sample-containing capillary was placed in melting
point apparatus and the temperature was increased
gradually. The temperature at which sample charred
completely was noted down as the charring point of
that sample.
Determination of the thiol group content
The thiol concentration on polymer conjugates and
controls were determined by iodometric titration. [9]
Each polymer (3.0 mg) was hydrated in 1.0 ml of
demineralized water. The pH was adjusted to between
2 and 3 by adding 1 M HCl. After the addition of
200μl of aqueous starch solution (1%; m/ v), samples
were titrated with an aqueous iodine solution 1.00
mM until a permanent light blue colour maintained.
Preparation of plain and conjugated
mucoadhesive buccal films
Buccal patches were prepared using solvent
casting technique [10, 11] using plain and conjugated
polymers. Different concentrations of polymers and
plasticizer glycerin were used in preparation of films;
the films of respective compositions were fabricated
using polymers along with drug and solvent. The
compositions of the formulated films were given in
the Table 1. Initially, films were prepared using only
plain chitosan and sodium alginate. The polymers
were weighed accurately, added to 30 ml of acetic
acid (1% v/v) and distilled water respectively, and
soaked for overnight and triturated until to form a
homogenous system then glycerin was added. The
drug was added to the above gel and triturated to form
a homogenous gel. In order to avoid entrapment of the
air bubbles inside the film, the entire gel was
subjected to sonication. Then these gels were cast into
poly ethylene coated glass petridish and allowed to
dry in a hot air oven with levelled surface maintained
at 40 °C till a flexible film was formed (48 h). The
dried films were cut into patches of 1cm2
and packed
in aluminium foil then stored in airtight desiccator
prior to use. These films were examined in order to
select the film having the best characteristics to
prepare conjugated buccal films.
EVALUATION OF THE PREPARED
FILMS
Content uniformity
To ensure uniform distribution of losartan
potassium in film, a content uniformity test was
performed. The film of 1cm2
was added to 50 ml of
Phosphate buffer (pH 6.8) contained in a 100 ml
volumetric flask was placed on mechanical shaker and
continuously shaked for 24 h. Then the solution was
filtered and the filtrate was examined for the drug
content by using UV-spectrophotometer (UV-1601,
SHIMADZU, Japan) at 227 nm. The experiments
were carried out in triplicate for the films of all
formulations and average values were taken as final
reading.
Film thickness
The diverging thickness of the films can
drastically alter the drug content. Uniform thickness is
highly important for the films composed of potent
drugs. The thickness of film was measured at different
positions with the help of Dail micrometer (Mitutoyo,
Japan) with the smallest possible unit measurement
count of 0.1 mm. The measurement was done for
about three films of each formulation and average
values were taken.
Weight variation
The formulated films were evaluated for their
uniformity in weights. Three films of every
formulation were randomly taken and weighed
individually on a digital balance. Average weight of
the films was noted as weight of the films.
Surface pH
Buccal patches were left to swell for 2 h on the
surface of an agar plate. The surface pH was
measured by means of a pH paper placed on the
surface of the swollen patch. A mean of three readings
was recorded.
Swelling studies [12]
Three patches were tested for each formulation.
The films of 1cm2
were weighted individually (Wo)
and placed separately in Petri dishes containing 5 ml
of phosphate buffer (pH 6.8) solution. At regular
intervals (1, 2, 3, 4, 5, 6, 7 and 8 h), the films were
removed from the Petri dishes and excess surface
water was removed care fully using the filter paper.
The swollen films were then reweighed (Wt) and
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28
swelling index (%S) was calculated using the
following formula:
Folding endurance
A modified USP tablet disintegrating tester was
used to determinine the folding endurance of the
membrane. [13] It consisted of fixed and movable
jaws that could be moved up and down at the rate of
30 strokes per minute. The distance between the 2
jaws at their farthest and closest were 6 centimeter
and 0.5 centimeter respectively. The membrane (6 cm
length) was clamped between the jaws in such a way
that the jaws were at their closest, the membrane
stretch across its middle and when at their farthest, the
membrane was in a stretched condition. Thus for
every stroke of the movable jaw the membrane went
through one cycle of bending and stretching. The
folding endurance is expressed as the number of
strokes required to either break or develop visible
cracks on the membrane. The test was conducted for
20 min equating 600 strokes. The examination was
done for about three films of each formulation and
average values were taken.
Bioadhesion force
The tensile strength required to detach the
bioadhesive film from the mucosal surface was
applied as a measure of the bioadhesive performance.
The apparatus was locally assembled and was a
modification of the apparatus previously described by
Parodi et al. [14] The device was mainly composed of
a two-arm balance. The left arm of the balance was
replaced by a small platinum lamina vertically
suspended through a wire. At the same side, a
movable platform was maintained in the bottom in
order to fix the model mucosal membrane. For
determination of the bioadhesion force, the
mucoadhesive film was fixed to the platinum lamina
using cyanoacrylate adhesive. A piece of goat buccal
mucosa, 3 cm long, was also glued to the platform.
The exposed film surface was moistened with 30 µl of
phosphate buffer (pH 6.8) and left for 30 seconds for
initial hydration and swelling. The platform was then
raised upward until the hydrated film was brought
into contact with the mucosal surface. A preload of 20
g was placed over the platinum lamina for 3 min as
initial pressure. On the right pan, a constant weight of
5 g was added at 2 min intervals. The total weight
required for complete detachment of the film was
recorded and the bioadhesion force was calculated per
unit area of the film as follows
Where “F” is the bioadhesion force (kgm-1
s-2
),
“Ww” is the mass applied (g), “g” is the acceleration
due to gravity (cm s-2
), and A is the surface area of the
film (cm2
). The adhesion force data reported represent
the mean of three determinations.
Residence time
The in vitro residence time was determined using
a locally modified USP disintegration apparatus. [15]
The disintegration medium was composed of 500
phosphate buffer (pH 6.8) maintained at 37 °C. A
segment of goat buccal mucosa, 3 cm long, was glued
to the surface of a glass slab, vertically attached to the
apparatus. The mucoadhesive film was hydrated from
one surface using 15 µl Phosphate buffer (pH 6.8) and
then the hydrated surface were brought into contact
with the mucosal membrane. The glass slab was
vertically fixed to the apparatus and allowed to move
up and down so that the film was completely
immersed in the buffer solution at the lowest point
and was out at the highest point. The time necessary
for complete erosion or detachment of the film from
the mucosal surface was recorded (mean of triplicate
determinations).
In vitro permeation studies
The modified Franz diffusion cell was used to
permeation studies, it consists of two compartments,
one is donar compartment and another is receptor
compartment of 18 ml capacity and having 0.785 cm2
effective surface area. The receptor compartment was
covered with jacket to maintain temperature 37 ºC.
The study was carried out on formulations using
dialysis membrane. [16] The dialysis membrane was
previously soaked for 12 h in the phosphate buffer
(pH 6.8). Then the film formulations of 1cm2
were
mounted between two chambers and in receptor
chamber phosphate buffer pH 6.8 was filled and tied
firmly with the help of rubber band to the specially
designed diffusion cell. The whole assembly was
placed on a magnetic stirrer, and the solution in the
receptor compartment stirred with the help of a teflon
coated bead at a constant speed and the temperature of
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29
whole assembly was maintained at 37 ± 0.5 ºC by
circulating hot water inside the water jacket. The
release study was carried out for 8 h. The samples (5
ml) were withdrawn and filtered at predetermined
intervals up to 8 h and replaced with Phosphate buffer
(pH 6.8) to maintain the sink conditions. The drug
content was analyzed with the help of UV-
spectrophotometer (UV-1601, SHIMADZU, Japan) at
227 nm. The experiment was repeated in triplicate for
all formulations.
Ex-vivo permeation studies
From the local slaughterhouse the buccal mucosa
was collected and immediately transported to the
laboratory in Ringer's solution. [17] The buccal
mucosa, with a part of submucosa, was carefully
separated from fat and muscle using scalpel. Then
buccal epithelium was isolated from the underlying
tissue and stabilized in phosphate buffer (pH 6.8). The
buccal epithelium was used with in 2 h upon removal.
The study was carried out on formulations using
buccal epithelium. This experiment was carried out
based on same procedure give in section.
Release Kinetics
In vitro release data were fit to following kinetic
equation to determine the order and mechanism of
drug release. [18, 19]
Zero order kinetics : Qt = Kot
First order kinetics : Qt = Qoe-Kt
Higuchi‟s square root model : Qt = KH√t
Where, Qt is amount of drug released at a time t,
Qo is the initial amount of drug in the dissolution
medium. K, Ko and KH are release constants.
In order to further determine the mechanism of
drug release, data was fit to Korsemeyer-Peppas
empirical power law equation. [20]
Mt/M∞ = Ktn
Where Mt/M∞ is the fraction of drug released at
time„t’, K is the structural and geometrical constant
and „n‟ is the release exponent.
When n = 0.5, fickian diffusion is observed and
the release rate is dependent on t, while in other
conditions 0.5 < n < 1 is consider to release drug by a
combination of drug diffusion as well as polymeric
chain relaxation (anomalous or non fickian transport).
When n=1, the drug release is considered to show
linearity towards zero order release kinetics.
Stability studies and ageing
Plain and drug loaded patches were packaged in
aluminium foil and stored in glass bottles closed with
screw caps. These bottles were subjected to
accelerated stability testing using stability chamber
(Remi instruments Ltd., Mumbai) maintained at 37º C
and 75 ± 5% RH for 1 month. Fresh and 1 month aged
medicated patches were evaluated.
RESULTS & DISCUSSION
Table 1: Composition of losartan potassium mucoadhesive buccal films
Formulation S1 S2 S3 S4 S5 S6 C1 C2 C3 C4 C5 C6 Cs Cc
Losartan
potassium (mg)
70 70 70 70 70 70 70 70 70 70 70 70 70 70
Sodium
alginate (mg)
450 600 600 600 600 600 0 0 0 0 0 0 0 0
Chitosan (mg) 0 0 0 0 0 0 450 600 600 600 600 600 0 0
Glycerin w/v 10% 10% 20% 30% 40% 50% 10% 10% 20% 30% 40% 50% 30% 30%
Conjugated
sodium alginate
(mg)
0 0 0 0 0 0 0 0 0 0 0 0 600 0
Conjugated
chitosan (mg)
0 0 0 0 0 0 0 0 0 0 0 0 0 600
Distilled water
(ml)
30 30 30 30 30 30 0 0 0 0 0 0 30 30
1% Acetic Acid
(ml)
0 0 0 0 0 0 30 30 30 30 30 30 0 0
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Calibration curve of losartan potassium
In this study, mucoadhesive buccal films of
losartan potassium were developed using polymers
like sodium alginate, chitosan, conjugated sodium
alginate and conjugated chitosan at different
concentrations. Glycerin was used as plasticizer, at
different weight ratios. The mucoadhesive buccal
films were prepared by solvent casting technique.
The calibration curve of losartan potassium was
developed in the range of 1 to 10 µg/ml at 227 nm.
Good linearity with a regression coefficient of 0.999
(r2
value) was observed. The tested concentration
range obeyed Beer‟s law (Figure 1).
Table 2: Concentration and absorbance obtained for calibration curve of losartan potassium.
Sl No Concentration (µg/ml) Absorbance (at 227 nm)
1 0 0
2 1 0.104±0.004
3 2 0.190±0.006
4 3 0.257±0.011
5 4 0.341±0.003
6 5 0.435±0.001
7 6 0.505±0.015
8 7 0.587±0.001
9 8 0.682±0.002
10 9 0.757±0.007
11 10 0.832±0.004
Values are mean±SD, n=3
Figure 1: Calibration curve of losartan potassium
CHARACTERISATION OF POLYMER
CONJUGATES
FT-IR study
The FTIR spectra of sodium alginate and thiolated
sodium alginate are shown in Figure 2 and 3, FTIR
spectrum of sodium alginate is attributed to its
saccharide structure. In addition, the bands at 1602
cm-1
and 1406 cm-1
are assigned to asymmetric and
symmetric stretching peaks of carboxylate salt groups.
In the spectra of conjugated sodium alginate the peak
at 1581.27 cm-1
was caused by carbonyl (C=O)
stretching of the amide and the absorption band at
2577.88 cm-1
corresponded to the thiol group (S-H)
y = 0.0824x + 0.0144
R² = 0.9991
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0 2 4 6 8 10
Absorbance
Concentration (µg/ml)
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31
stretching which were compared with the IR spectra
of the pure sodium alginate polymer and found that
these characteristic peaks were absent in pure sodium
alginate polymer. [21, 22] It was observed from the
spectra of the conjugated sodium alginate that the
band represented thiol group (S-H) stretching (at
2577.88 cm-1
) confirmed the conjugation of sodium
alginate with cysteine and the peak caused by
carbonyl (C=O) stretching of amide bond (at
1527.67 cm-1
) which has confirmed that the
conjugation has occurred through the amide linkage
only. The FTIR spectra of conjugated chitosan,
showed the bands representing the -C=O stretching of
amide bond (at 1645.45 cm-1
) and -SH stretching (at
2664.24 cm-1
) which were absent in the FTIR spectra
of the chitosan. [23] The additional peaks in the FTIR
spectra of the conjugated chitosan have confirmed the
conjugation of chitosan with TGA. The FT-IR spectra
of chitosan and conjugated chitosan are shown in
figure 4 and 5.
Figure 2: FT-IR spectrum of pure sodium alginate polymer
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32
Figure 3: FT-IR spectrum of conjugated sodium alginate polymer
Figure 4: FT-IR spectrum of pure chitosan polymer
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33
Figure 5: FT-IR spectrum of conjugated chitosan polymer
Determination of the thiol group content
The degree of modification by the covalent
attachment of cysteine to alginate and thioglycolic
acid to chitosan was quantified by iodometric
titration, to determine free thiol groups and
conformation of polymer conjugates. The alginate–
cysteine conjugate displayed 475.64±24.31 µmol thiol
groups per g polymer. The chitosan thoglycolicacid
conjugate displayed 305±31.21 µmol thiol group per
g polymer. The presence of thiol groups in both
polymers confirmed sodium alginate-cysteine and
chitosan-thioglycolic acid conjugation (Figure 6).
Figure 6: Resulted thiol group content of conjugated polymers
0
100
200
300
400
500
600
Conjugated sodium
alginate
Conjugated chitosan
Thiolgroupsµmolpergram
polymer
Conjugated sodium alginate
Conjugated chitosan
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Characteristics of developed formulations
Physical characteristics of the formulated
losartan potassium mucoadhesive buccal
films.
Table 3 summarizes the physical characteristics of
the formulated films. All the formulations exhibited
fairly uniform drug content and ranged from 95.29 ±
0.01% to 98.63 ± 0.21%. The drug content in each of
the film was found to be high (>90 %) suggesting a
high retaining capacity of losartan potassium that will
be available to permeate transbuccally. Formulation
procedures involve fewer processing steps, no major
drug loss was observed during the preparation of the
films. All the films were found to be with uniform
thickness and weight variation. The uniform thickness
and weight of the films suggested the uniform
distribution of drug and polymer over the surface
selected for film-forming. The thicknesses of all
formulated films were observed to be in the range of
0.37±0.12mm to 0.61±0.05mm and weight was found
to be in the range of 19±0.61 mg to 43±0.78 mg.
From this study it was observed that with increase in
plasticizer concentration the thickness and weight was
found to increase gradually.
Considering the fact that acidic or alkaline pH
may cause irritation to the buccal mucosa and
influence the degree of hydration of polymers, the
surface pH of the buccal films was determined to
optimize both drug permeation and mucoadhesion.
The surface pH of all formulations was observed to be
in the range of 6.4±0.12 to 6.9±0.27 which are within
the range of salivary pH. No significant difference
was found in surface pH of different films.
Swelling studies and mechanical properties of
formulated losartan potassium mucoadhesive
buccal films.
Hydration is required for a mucoadhesive polymer
to expand and create a proper macromolecular mesh
of sufficient size, and also to induce mobility in the
polymer chains in order to enhance the
interpenetration process between polymer and mucin.
Polymer swelling permits a mechanical entanglement
by exposing the bioadhesive sites for hydrogen
bonding and/or electrostatic interaction between the
polymer exists where optimum swelling and
bioadhesion occurs. [24]
Effect of polymer concentration and
composition on swelling in non-conjugated
polymers
Table 4 showed the swelling index % of losartan
potassium mucoadhesive films containing different
bioadhesive polymers (sodium alginate, chitosan). It
was found that sodium alginate films (S1 to S6) had
the highest swelling index % in range of 136.24±0.32
to 153.18±0.31 after 8 h and chitosan films (C1 to C6)
had the least swelling index % in range of 89.55±0.12
to 92.64±0.24 after 8 h. The low solubility of chitosan
above pH 6 might have limited the swelling of films
and Chitosan has a rigid structure and can allow little
amount of water molecules to penetrate the matrix.
The hydrophilic polymer sodium alginate increased
the surface wettability and consequently water
penetration within the matrix. As sodium alginate is
hydrophilic polymer and has ability to absorb water
so maximum swelling index % was seen with
Formulations containing sodium alginate (S1 to S6) as
compared with formulations containing chitosan (C1
to C6).
The rate and extent of swelling of films increased
with an increasing concentration of sodium alginate.
Formulation S2 containing sodium alginate 600 mg
exhibited the highest swelling index 155.21±0.13
while formulation S1 having lowest concentration of
sodium alginate 450 mg exhibited swelling index
136.24±0.32 after 8 h. It was found that chitosan films
containing chitosan 600 mg had the swelling index
92.46±0.47 after 8 h and films containing 450 mg of
chitosan had the swelling index 79.55±0.12. It was
observed that the films containing more amount of
polymer shows more swelling index, this would be
due to more swelling of polymers and hold more
amount of water in their network.
Effect of conjugation on Swelling
The effect of conjugation on the swelling behavior
of various mucoadhesive polymers was observed
(table 4). The conjugated polymeric films showed
high swelling index in comparison to films containing
non-conjugated polymers. The conjugated sodium
alginate films (Cs) showed the swelling index of
298.46±0.13 after 8 h, whereas those made with pure
sodium alginate (S1 to S6) showed maximum
swelling index 154.46±0.12 after 8 h, respectively.
The conjugated chitosan films (Cc) showed the selling
index 238.43±0.21 after 8 h, whereas those made with
pure chitosan (C1 to C6) showed maximum swelling
index 93.68±0.16 after 8 h.
In case of conjugated sodium alginate conjugated
chitosan due to presence of thiol group in place of
primary amino group of chitosan the polymer chain
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35
gets opened and forms a loose matrix which allows
more number of water molecules to penetrate. Hence
the swelling index of film with conjugated polymer
was found to be increased compared with films
contained pure polymers.25
Folding endurance
The folding endurance measures the breaking
ability of the films during use. Sufficient folding
endurance (> 300) times was found for the all
formulated films of each batch, suggesting the use of
the system for a period of 24 h or more without
breaking or cracking (Table 4). This might be due to
adequate content of glycerin which provides it with
high mechanical strength and good elasticity.
Table 3: Physical characteristics of losartan potassium mucoadhesive buccal films.
Formulation Weight (mg) Thickness (mm) Surface pH Drug content (%)
S1 19±0.61 0.37±0.12 6.7±0.23 98.63±0.21
S2 22±0.48 0.41±0.24 6.6±0.25 97.34±0.07
S3 26±0.37 0.43±0.15 6.7±0.31 96.21±0.17
S4 29±0.21 0.46±0.07 6.8±0.38 98.28±0.31
S5 32±0.05 0.49±0.14 6.7±0.12 97.12±0.08
S6 36±0.14 0.51±0.08 6.6±0.35 98.29±0.47
C1 21±0.42 0.39±0.02 6.4±0.12 95.13±0.14
C2 24±0.16 0.43±0.24 6.5±0.14 94.14±0.02
C3 29±0.08 0.46±0.17 6.5±0.12 96.29±0.25
C4 33±0.67 0.48±0.21 6.4±0.26 94.03±0.13
C5 36±0.29 0.52±0.04 6.6±0.18 93.43±0.18
C6 39±0.07 0.56±0.11 6.5±0.07 95.29±0.01
Cs 41±0.54 0.59±0.24 6.9±0.27 98.21±0.24
Cc 43±0.78 0.61±0.05 6.8±0.16 97.44±0.54
Values are mean±SD, n=3
Table 4: Swelling studies and mechanical properties of losartan potassium mucoadhesive buccal films.
Formulation Swelling Index
(%)
After 8 h
Bioadhesive
Strength (g)
Force of
Adhesion (N)
Folding
Endurance
In vitro residence
time (h)
S1 136.24±0.32 19.67±0.32 0.192±0.07 300 7.43±0.43
S2 155.21±0.13 21.83±0.43 0.214±0.01 300 8
S3 154.11±0.08 21.66±0.37 0.212±0.04 300 8
S4 154.46±0.12 22.21±0.56 0.217±0.12 300 8
S5 154.23±0.03 21.43±0.27 0.210±0.17 300 8
S6 153.18±0.31 21.33±0.16 0.209±0.08 300 8
C1 79.55±0.12 13.34±0.34 0.130±0.26 300 8
C2 92.46±0.47 14.52±0.54 0.142±0.04 300 6.32±0.75
C3 93.68±0.16 14.15±0.21 0.138±0.42 300 8
C4 92.91±0.02 14.42±0.19 0.141±0.18 300 8
C5 93.07±0.18 14.84±0.47 0.145±0.13 300 8
C6 92.64±0.24 14.53±0.37 0.142±0.24 300 8
Cs 298.46±0.13 32.32±0.26 0.317±0.27 300 8
Cc 238.43±0.21 28.92±0.12 0.283±0.06 300 8
Values are mean±SD, n=3
12. Ravuri Sandeep et al / Int. J. of Farmacia, 2017; Vol-(3) 1: 25-43
36
BIOADHESIVE STUDIES
Effect of polymer concentration and
composition on bioadhesive strength in non-
conjugated polymers
Table 4 showed the bioadhesive strength of
losartan potassium mucoadhesive films containing
different bioadhesive polymers (sodium alginate,
chitosan). From comparision studies between these
two polymers, it was found that sodium alginate films
(S1 to S6) had the highest bioadhesive strength in
range of 19.67±0.32 (g) to 21.33±0.16 (g) and
chitosan films (C1 to C6) had the least bioadhesive
strength in range of 13.34±0.34 (g) to 14.53±0.37 (g).
The polymeric nature of sodium alginate provides
the polymer with unique gelling characteristics, which
in turn are responsible for its adhesive properties, in
addition to its rapid swelling, high mechanical
strength, high water uptake, and high elasticity.
Linear chains of sodium alginate exhibit strong
bioadhesive behavior either because of hydrogen
bonding due to hydroxyl groups or because of
significant chain penetration. Chitosan is a promising
bioadhesive material at neutral or slightly alkaline pH,
which is found to be advantageous for adsorption on
the mucosal surface. It was suggested that, at this pH,
chitosan has numerous amine and hydroxyl groups as
well as a number of amino groups that may increase
the interaction with the negative mucin. Additionally,
chitosan in general has mucoadhesive properties
because of its positive charge. [26] The electrostatic
attraction between the positively charged chitosan and
the negatively charged mucus was demonstrated.
Chitosan has less swelling and gelling properties as
compared to sodium alginate this is may be the reason
that the chitosan films showed less bioadhesive
properties towards porcine buccal mucosa than
sodium alginate films (figure 7).
Effect of conjugation on bioadhesive strength
The effect of conjugation on the bioadhesive
properties of various mucoadhesive polymers was
observed (table 4). The conjugated polymeric films
showed high bioadhesive strength and work of
adhesion in comparision to films containing non-
conjugated polymers.
In Figure, the conjugated sodium alginate films
(Cs) showed the bioadhesive strength (g) 32.32±0.26,
whereas those made with pure sodium alginate (S1 to
S6) showed maximum bioadhesive strength
22.21±0.56 (g), respectively. The conjugated chitosan
films (Cc) showed the bioadhesive strength
238.43±0.21 (g), whereas those made with pure
chitosan (C1 to C6) showed maximum bioadhesive
strength 93.68±0.16 (g).
Bioadhesive studies carried out with alginate,
chitosan and the alginate–cysteine conjugate and
chitosan-thioglycolic revealed a strong influence of
covalently attached cysteine and thioglycolic acid on
the mucoadhesive properties of the polymer. Because
of the immobilized thiol groups being capable of
forming disulfide bonds with mucus glycoproteins the
mucoadhesiveness of the conjugated polymer was
more than that of the unmodified original polymer.
The results of adhesion studies are shown in figure 7.
A rapid swelling behaviour of mucoadhesive
polymers favours the interdiffusion process between
the polymer and the mucus layer providing stronger
adhesion than it is the case for poorly swelling
polymers. [27] Accordingly, the swelling behaviour
has an influence on the adhesive properties of a
polymer. Swelling studies were therefore carried out
with the conjugated polymers and un- modified
polymers. The results as shown in figure 7
demonstrate that the covalent attachment of cysteine
to the polymer leads to a significant increase in the
swelling behaviour of the polymer. This improved
water uptake of the conjugate should contribute to the
mucoadhesiveness of the thiolated polymer.
In vitro residence time
In vitro residence time data as represented in
Table 4, none of the formulations were detached from
the oral mucosa over the study period, which
indicated that the bioadhesion values of all
formulations were satisfactory to retain the film on
the buccal mucosa.
13. Ravuri Sandeep et al / Int. J. of Farmacia, 2017; Vol-(3) 1: 25-43
37
Figure 7: Bioadhesive studies of formulated losartan potassium mucoadhesive buccal films
In vitro permeation studies of formulated
losartan potassium mucoadhesive buccal films
The release profile of losartan potassium films
were illustrated in figures 8 and 9. The cumulative
percent drug permeated from the formulations S1, S2,
S3, S4, S5 and S6 was found to be 96.07±0.64%,
88.58±0.23%, 91.72±021%, 93.34±0.52%,
97.33±0.18% and 89.61±0.48%, respectively in 6 h.
The cumulative percent drug permeated of films
decreased with an increasing concentration of sodium
alginate (figure 8). Formulation S2 containing sodium
alginate 600 mg exhibited the cumulative percent
drug permeation of 96.07 ±0.64 while formulation S1
having lowest concentration of sodium alginate 450
mg exhibited drug permeation of 88.58±0.23.
Conversely, a higher glycerin percent increased the
drug permeation, [28] particularly at a polymer
concentration of 10 to 30% w/v (S2, S3, S4 and S5).
A further increase of glycerin percent (40 to 50% w/v)
did not improve losartan potassium permeation (S6).
From drug permeation studies of the formulations S1,
S2, S3, S4, S5 and S6 it was found that all the
formulation showed burst drug permeation at end of 2
h followed by sustained drug permeation up to 6 h.
This could be attributed to the higher rate and extent
of swelling of the hydrophilic polymer, sodium
alginate and also due to the hydrophilic nature of
drug.
Chitosan-containing films (C1 to C6) produced
sustained permeation of drug up to 8 h in all
formulations (Figure 9). The cumulative percent drug
permeated from the formulations C1, C2, C3, C4, C5
and C6 was found to be 57.52±0.87%, 46.49±0.64%,
48.78±0.31%, 52.34±0.47%, 50.73±0.62% and 46.98
±0.81%, respectively in 8 h. The cumulative percent
drug permeated of films decreased with an increasing
concentration of chitosan (figure 9). Formulation C2
containing chitosan 600 mg exhibited the cumulative
percent drug permeation of 46.49±0.64 % while
formulation C1 having lowest concentration of
sodium alginate 450 mg exhibited drug permeation of
57.52±0.87%. Conversely, a higher glycerin percent
increased the drug permeation, particularly at a
polymer concentration of 10 to 30% (w/v) (C2, C3,
and C4). A further increase of glycerin percent (40 to
50% w/v) did not improve losartan potassium
permeation (C5 and C6). From drug permeation
studies of the formulations C1, C2, C3, C4, C5 and
C6 it was found that all the formulation showed
sustained drug permeation up to 8 h. This could be
attributed to the low rate and extent of swelling of the
water insoluble polymer, chitosan. The effect of
polymer composition on drug permeation of various
mucoadhesive polymers was observed (sodium
alginate and chitosan). The sodium alginate films (S1
to S6) showed high drug permeation in the range of
89.61±0.48% to 97.33±0.18% with in 6 h where as
0
5
10
15
20
25
30
35
SI S2 S3 S4 S5 S6 C1 C2 C3 C4 C5 C6 Cs Cc
Bioadhesivestrength(g)
Formulation code
14. Ravuri Sandeep et al / Int. J. of Farmacia, 2017; Vol-(3) 1: 25-43
38
those films which containing chitosan (C1 to C6)
showed sustained drug permeation in the range of
46.49±0.64% to 57.52±0.87% up to 8 h. From the
release profile it is clearly evident that the drug
permeation was more and quick for hydrophilic and
rapid swellable polymer polymer as compare to
hydrophobic and less swellable polymer chitosan
(Figures 8 and 9). The effect of conjugation on the
drug permeation of various mucoadhesive polymers
was observed (sodium alginate and conjugated
sodium alginate). The conjugated polymeric films
showed sustained and slow drug release in
comparisons to films containing non-conjugated
polymers. In Figure 9, the conjugated sodium alginate
films (Cs) showed the cumulative percent drug
permeation of 82.87±0.53% after 8 h whereas those
made with pure sodium alginate (S1 to S6) showed
maximum cumulative percent drug permeation of
97.33±0.18% respectively, within 6 hours.(figure 12).
The formation of disulfide bonds just within the
thiolated polymer itself, leading also to an increase of
viscosity. [29] Due to the high viscosity, high
bioadhesion properties and high cohesiveness of
conjugated sodium algnate (Cs) showed sustained and
slow release up to 8 h. In Figure 9, the conjugated
chitosan films (Cc) showed the cumulative percent
drug permeation of 74.48±0.69% after 8 h whereas
those made with pure chitosan (S1 to S6) showed
maximum cumulative percent drug permeation of
57.52±0.43% respectively, within 8 hours. The
conjugated polymeric films showed sustained and
more drug release in comparision to films containing
non-conjugated polymers. This is due to the property
of conjugated chitosan in which the primary amino
group is replaced by thiol group of thioglycolic acid,
which results in opening of polymer chain and
increasing swelling index, moisture content, moisture
uptake, permeation coefficient and results in increased
drug permeation. [30] Formulations S5, C4, Cs and
Cc showed good swelling, high bioadhesive
properties, a convenient residence time as well as
promising drug permeation pattern. On the basis of
drug permeation pattern, swelling, bioadhesion
properties and residence time, S5, C4, Cs and Cc
formulations were selected for ex vivo study.
Ex vivo permeation studies of formulated
losartan potassium mucoadhesive buccal films
In ex vivo study, drug permeation through the goat
buccal mucosa was determined for optimized
formulations S5, C4, Cs and Cc. The optimized
formulations S5, C4, Cs and Cc cumulative
percentage drug permeation rates are 97.33±0.18%,
48.78±0.31%, 82.87±0.53% and 74.48±0.69%
through the dialysis membrane and the cumulative
percentage drug permeation rates through goat buccal
mucosa are 92.33±0.265%, 45.78±0.52%,
77.87±0.43%, and 70.48±0.76% respectively; results
of the same are shown in figures 10-13. From the
results we can conclude that the permeation through
the biological membrane is less than that of dialysis
membrane because of the presence of epithelial
membrane.
In vitro permeation studies of formulated losartan potassium mucoadhesive buccal films
Figure 8: In vitro drug permeation of formulations S1 to S6 and Cs
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8
Cumulative%drugrelease
Time (h)
S1
S2
S3
S4
S5
S6
Cs
15. Ravuri Sandeep et al / Int. J. of Farmacia, 2017; Vol-(3) 1: 25-43
39
Figure 9: In vitro drug permeation of formulations C1 to C6 and Cs
Ex vivo permeation studies of formulated losartan potassium mucoadhesive buccal films
Figure 10: Comparision of in vitro and ex vivo permeation of formulation S5
0
10
20
30
40
50
60
70
80
0 1 2 3 4 5 6 7 8
Cumulative%drugrelease
Time (h)
C1
C2
C3
C4
C5
C6
Cc
0
20
40
60
80
100
120
0 1 2 3 4 5 6 7
Cumulative%drugrelease
Time (h)
In-vitro
Ex-vivo
16. Ravuri Sandeep et al / Int. J. of Farmacia, 2017; Vol-(3) 1: 25-43
40
Figure 11: Comparision of in vitro and ex vivo permeation of formulation Cs
Figure 12: Comparision of in vitro and ex vivo permeation of formulation C3
Figure 13: Comparison of in vitro and ex vivo permeation of formulation C
0
10
20
30
40
50
60
70
80
90
0 1 2 3 4 5 6 7 8 9
Cumulative%drugrelease
Time (h)
In-vitro
Ex-vivo
0
10
20
30
40
50
60
0 1 2 3 4 5 6 7 8 9
Cumulative%drugrelease
Time (h)
In-vitro
Ex-vivo
0
10
20
30
40
50
60
70
80
0 1 2 3 4 5 6 7 8 9
Cumulative%drugrelease
Time (h)
In-vitro
Ex-vivo
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41
Kinetics of drug permeation from formulated
losartan potassium mucoadhesive buccal films
Release data analysis
To analyse the mechanism of drug release from
losartan potassium mucoadhesive buccal films, the
drug permeation data were fitted to various kinetics
models (table 5). Formulations S1 to S6 of pure
sodium alginate followed first order kinetics and the
formulation contains conjugated sodium alginate Cs
also followed first order kinetics. Formulations C2,
C3, C4 and C6 of pure chitosan followed zero order
kinetics, while the formulations C1 followed first
order kinetics. In case of conjugated chitosan
containing formulation Cc also followed zero order
kinetics.
The results of drug release mechanism are
represented in Table 5. This claim was made on the
basis of the n values obtained by Korsmeyer‟s plot,
for non-Fickian release, the value of n falls between
0.5 and 1.0; while in the case of Fickian diffusion, n =
0.5; and for (super case II), n >1. Sodium alginate
containing films (S1 to S6) showed n values in the
range of 0.755 to 0.798, these values indicated the
mechanism of drug permeation was found to be by
non-Fickian diffusion. In case of chitosan containing
films (C1 to C6) showed n values in the range of
1.003 to 1.050, these values indicated the mechanism
of drug permeation was found to be by super case II
kinetics. While in case of conjugated chitosan and
conjugated sodium alginate containing films (Cs and
Cc) showed n values 0.742 and 0.750, these values
indicated the mechanism of drug permeation was
found to be by non-Fickian diffusion.
Table 5: Drug release kinetics from different formulations of losartan potassium mucoadhesive buccal
films.
Formulation Zero order First order Higuchi Release exponent (n)
S1 0.921 0.979 0.977 0.798
S2 0.923 0.999 0.978 0.779
S3 0.939 0.995 0.978 0.787
S4 0.934 0.993 0.979 0.773
S5 0.918 0.981 0.978 0.776
S6 0.929 0.997 0.982 0.755
C1 0.986 0.994 0.967 1.024
C2 0.997 0.996 0.934 1.003
C3 0.998 0.995 0.928 1.050
C4 0.998 0.992 0.922 1.044
C5 0.997 0.994 0.926 1.019
C6 0.994 0.995 0.926 1.046
Cs 0.988 0.987 0.965 0.742
Cc 0.957 0.996 0.988 0.750
Stability studies
Stability studies were carried out for the selected
formulations (S5, C4, Cs and Cc). Results of the
stability studies are shown in figures and it was found
that, there was no significant difference in drug
content and in vitro permeation profiles of both
formulations and they were almost similar to release
profiles of both formulations and they were almost
similar to release profiles obtained during initial
studies as shown in figures 18-21.
Table 8: Drug content of formulations S5, C4, Cs and Cc before and after stability studies
Drug content
Formulation initially After stability studies
S5 97.12±0.08 96.48±0.12
C4 94.03±0.13 92.36±0.08
Cs 98.21±0.24 97.72±0.16
Cc 97.44±0.54 96.14±0.05
18. Ravuri Sandeep et al / Int. J. of Farmacia, 2017; Vol-(3) 1: 25-43
42
CONCLUSION
The conjugation of polymers (sodium alginate-
cysteine and chitosan-thioglycolic acid) were
confirmed by FTIR study. Good results were obtained
both in vitro and ex vivo conditions for optimized
films. A higher glycerin percent in films increased the
drug permeation, particularly at a polymer
concentration of 10 to 30% w/v. A further increase of
glycerin percent (40 to 50% w/v) did not improve
losartan potassium permeation. Formulations
containing conjugated sodium alginate and chitosan
resulted in a significantly higher bioadhesion,
swelling with better drug permeation over long period
than films comprising unmodified polymers. The ex
vivo studies has shown promising results and further
in vivo studies need to be designed and executed to
substantiate further in vitro–in vivo correlation.
BIBLIOGRAPHY
[1]. Krauland AH, Guggi D, Schnurch AB. Thiolated chitosan microparticles: A vehicle for nasal peptide drug
delivery. Int J Pharm.307, 2006, 270–77.
[2]. Dunnhaupt S, Barthelmes J, Hombach J, Sakloetsakun D, Arkhipov V, SchnurchAB. Distribution of thiolated
mucoadhesive nanoparticles on intestinal mucosa. Int J Pharm.408, 2011, 191-99.
[3]. Johnston C. Angiotensin receptor antagonists: focus on losartan. Lancet.346, 1995, 1403-07.
[4]. Thakur R, Anwer MK, Shams MS, Ali A. Proniosomal transdermal therapeutic system of losartan potassium:
development and pharmacokinetic evaluation. J Drug Target. 17(6), 2009, 442-49.
[5]. Palmberger TF, Hombach J, Schnurch AB. Thiolated chitosan: Development and in vitro evaluation of an oral
delivery system for acyclovir. Int J Pharm. 348, 2008, 54-60.
[6]. Kast CE, Schnurch AB. Thiolated polymers- thiomers: development and in vitro evaluation of chitosan
thioglycolic acid conjugates. Biomaterials. 22, 2001, 2345-52.
[7]. Schnurch AB, Scholler S, Biebel RG. Development of controlled drug release systems based on thiolated
polymers. J Control Rel. 66, 2000, 39-48.
[8]. Schnurch AB, Kast CE, Richter MF. Improvement in the mucoadhesive properties of alginate by the covalent
attachment of cysteine. J Control Rel. 71, 2001, 277-85.
[9]. Langoth N, Kalbe J, Schnurch AB. Development of buccal drug delivery systems based on a thiolated polymer.
Int J Pharm. 252, 2003, 141-48.
[10]. Grabovac V, Foger F, Schnurch AB. Design and in vivo evaluation of a patch delivery system for insulin based
on thiolated polymers. Int J Pharm. 348, 2008, 169-74.
[11]. Nafee NA, Ismail FA, Boraie NA, Mortada LM. Mucoadhesive buccal patches of miconazole nitrate: in vitro/in
vivo performance and effect of ageing. Int J Pharm. 264, 2003, 1-14.
[12]. Patel RS, Poddar SS. Development and characterization of mucoadhesive buccal patches of salbutamol
sulphate. Current Drug Del. 6, 2009, 140-44.
[13]. Satishbabu BK, Srinivasan BP. Preparation and valuation of buccoadhesive films of Atenolol. Ind J Pharm Sci.
2008, 175-79.
[14]. Nafee NA, Boraie NA, Ismail FA, Mortada LM. Design and characterization of mucoadhesive buccal patches
containing cetylpyridinium chloride. Acta Pharm. 53, 2003, 199-212.
[15]. Semalty M, Semalty A, Kumar G. Formulation and characterization of mucoadhesive buccal films of glipizide.
Ind J Pharm Sci. 70(1), 2008, 43-48.
[16]. Averineni RK, Sunderajan SG, Mutalik S, Nayak U. Development of mucoadhesive buccal films for the
treatment of oral sub-mucous fibrosis: a preliminary study. Pharm Dev Tech. 14(2), 2009, 199-207.
[17]. Hassan N, Ali M, Ali J. Novel buccal adhesive system for anti-hypertensive agent Nimodipine. Pharm Dev
Tech. 15(2), 2010, 124-130.
[18]. Krauland AH, Guggi D, Schnurch AB. Thiolated chitosan microparticles: A vehicle for nasal peptide drug
delivery. Int J Pharm. 307, 2006, 270-77.
[19]. Chandrasekar MJN, Kumar SM, Manikandan D, Nanjan MJ. Isolation and evaluation of a polysaccharide from
Prunus amygdalus as a carrier for transbuccosal delivery of Losartan potassium. Int J Biological
Macromolecules. 48, 2011, 773-78.
19. Ravuri Sandeep et al / Int. J. of Farmacia, 2017; Vol-(3) 1: 25-43
43
[20]. Shams MS, Alam MI, Ali A, Sultana Y, Aqil M, Shakeel F. Pharmacokinetics of a losartan potassium released
from a transdermal therapeutic system for the treatment of hypertension. Pharmazie. 65, 2010, 679-82.
[21]. Ping Li, Dai YN , Zhang JP, Wang AQ, Wei Q. Chitosan-alginate nanoparticles as a novel drug delivery system
for nifedipine. Int J Biomed Sci. 4(3), 2008, 221-28.
[22]. Silverstein RM, Webster FX. Spectrometric identification of compounds. John Wiley and Son‟s, Inc. 6, 96-107.
[23]. Osman Z, Arof AK. FTIR studies of chitosan acetate based polymer electrolytes. Electrochimica Acta. 48,
2003, 993-99.
[24]. Mohanan A, Vishlakshi B. Swelling and diffusion characteristics of interpenetrating network film composed of
sodium alginate and gelatin: transport of azure B. Int J Polym Mat. 58, 2009, 561-80.
[25]. Schnurch AB, Krauland AH, Leitner VM, Palmberger T. Thiomers: potential excipients for non-invasive
peptide delivery systems. Eur J Pharm Biopharm. 58, 2004, 253-63.
[26]. Yehia SA, Basalious EB. Fluconazole mucoadhesive buccal films: In Vitro/In Vivo Performance. Current Drug
Del. 6, 2009, 17-27.
[27]. Schnurch AB, Hornof M, Zoidl T. Thiolated polymers-thiomers: synthesis and in viro evaluation of chiosan-2-
iminothiolane conjugates. Int J Pharm. 260, 2003, 229-37.
[28]. Pignatello R, Basile L, Puglisi G. Chitosan glutamate hydrogels with local anesthetic activity for buccal
application. Drug Del. 16(3), 2009, 176-81.
[29]. Schnurch AB. Thiomers: A new generation of mucoadhesive polymers. Adv Drug Del Rev. 57, 2005, 1569-82.
[30]. Rahmat D, Sakloetsakun D, Shahnaz G, Perera G. Design and synthesis of novel cationic thiolated polymer. Int
J Pharm. 2011, 1-8.