Preparation and Evaluation of Directly-Compressed Indomethacin, Indomethacin Sodium and Indomethacin Meglumine Tablets

A formula containing Compactrol, Ac-Di-Sol, Aerosil 200 and talc was used to prepare directly-compressed tablets of indomethacin and its sodium and meglumine salts. The prepared tablets were evaluated for uniformity of weight and thickness, hardness, friability and content uniformity. Each batch was then divided into two, one was coated with an opaque non-enteric film coat and evaluated for coat thickness uniformity. The dissolution rates of the uncoated and coated tablets and the effect of shelf-storage, at room temperature for 11 months, on drug contents were also studied. Indomethacin meglumine tablets showed the least relative standard deviation of weight and thickness. They exhibited acceptable uniformity of content and coat thickness, and the highest hardness-friability ratio. Also exhibited, uncoated and coated, the best in-vitro release of its drug contents and the maximal stability.     

In-Vivo Evaluation of a Bioadhesive Containing Indomethacin Tablets

The relative bioavailability of a bioadhesive containing, directly compressed, tablet formulation against the commercial indomethacin capsules “Indocid, MSD” has been investigated in dogs. The tablets showed a prolongation of the time to reach maximum concentration to 3 hours compared to 2 hours in capsules. They also showed 39% and 184% increase in maximum and minimum plasma concentration, respectively. The relative bioavailability of the tablets is 152% compared to capsules where the tablets showed a mean area under the plasma concentration-time curve of 26 ug.hr/ml compared to 17 ug.hr/ml for capsules.     

In-Vivo Evaluation of a Bioadhesive Containing Indomethacin Tablets

The relative bioavailability of a bioadhesive containing, directly compressed, tablet formulation against the commercial indomethacin capsules “Indocid, MSD” has been investigated in dogs. The tablets showed a prolongation of the time to reach maximum concentration to 3 hours compared to 2 hours in capsules. They also showed 39% and 184% increase in maximum and minimum plasma concentration, respectively. The relative bioavailability of the tablets is 152% compared to capsules where the tablets showed a mean area under the plasma concentration-time curve of 26 ug.hr/ml compared to 17 ug.hr/ml for capsules.     

Preparation and Pharmacodynamic Evaluation of Liposomes of Indomethacin

The side effects of indomethacin, such as ulceration of the kidney and central nervous system (CNS) toxicity, limit its use as a drug for rheumatoid arthritis. Encapsulation of this drug in liposomes may reduce the toxic effects. The aim of this study was to determine the factors influencing encapsulation of indomethacin in liposomes and to determine anti-inflammatory potential of liposomal indomethacin. A series of liposomal formulations of indomethacin were prepared using various phospholipids. The effects of method of preparation, lipid composition, charge, and cholesterol (CH) on encapsulation of indomethacin in liposomes were investigated. A significant variation in encapsulation of the drug in liposomes was observed when prepared by different methods. With all the methods of preparation tried, the favorable lipid compositn for high encapsulation of this drug was egg phosphatidyl choline:CH:stearlyamine (PC:CH:SA) at a 1:0.5:0.1 molar ratio. Inclusion of cholesterol did not affect the encapsulation efficiency of the drug in liposomes. The drug release profile from the liposomes was biphasic, and the highest percentage drug release was observed with large unilamellar vesicles (LUVs) (100 nm). Inclusion of steary-Ujylamine (PC:CH:SA 1:0.5:0.1) and phosphatidyl glycerol (PG) (PC:CH:PG:1:0.5:0.2) in the liposomes reduced the release of the drug in comparison to the neutral liposomes (PC:CH 1:1). The slow release of the drug from stearylamine-containing liposomes may be explained by the electrostatic interaction between the acid moiety of the drug and the amine moiety of the lipid. It is assumed that the possible hydrogen bonding between –OH groups of phosphatidyl glycerol and the –COOH group of the drug might be the reason for the slow release of the drug from PC:CH:PG (1:0.5:0.2) containing liposomes. Pharmacodynamic evaluation of the liposomes was performed by carrageenan-induced rat paw edema (acute) and adjuvant arthritis (chronic) models. The anti-inflammatory activity was increased from the first to fifth hour PC:CH:PG (1:0.5:0.2) and PC:CH:SA(1:0.5:0.1) liposomes showed the highest percentage inhibition of edema. In both these models, anti-inflammatory activity of liposomal indomethacin was significantly higher than that of free indomethacin (p <. 01). The ulcer index of the free drug was about three times more than the encapsulated drug when administered at the same dose intraperitoneally to arthritic rats consecutively for 21 days.     

Preparation and Evaluation of Controlled Release Indomethacin Microspheres

Microspheres containing indomethacin were prepared with various combinations of polymers Eudragit RS and Eudragit L. The effects of different ratios of polymers, solvent-polymer ratio, polymer-drug ratio and evaporation temperature on the physical characteristics of the microspheres as well as the in vitro release rate of the drug were investigated. All the factors studied had an influence on the physical characteristics of the microspheres. In vitro dissolution results showed that all formulations gave prolonged release of indomethacin and the release followed apparent zero order kinetics until 80% of drug had been released.     

Preparation and Evaluation of Controlled Release Indomethacin Microspheres

Abstract

Microspheres containing indomethacin were prepared with various combinations of polymers Eudragit RS and Eudragit L. The effects of different ratios of polymers, solvent-polymer ratio, polymer-drug ratio and evaporation temperature on the physical characteristics of the microspheres as well as the in vitro release rate of the drug were investigated. All the factors studied had an influence on the physical characteristics of the microspheres. In vitro dissolution results showed that all formulations gave prolonged release of indomethacin and the release followed apparent zero order kinetics until 80% of drug had been released.     

Preparation and Evaluation of Sustained release Indomethacin Nonpareil Seeds

Abstract

A controlled release oral drug delivery system of Indomethacin was developed using nonpareil seeds as a matrix system. These seeds were coated with different concentrations of drug release controlling materials viz Eudragit RL100 and Eudragit RS100, and bees wax. The particle size of the seeds and the concentration as well as the type of the drug release controlling Eudragits has a pronounced effect on the release rate profile of Indomethacin. All types of formulations showed release rate pattern which can be described by both first-order and diffusion controlled mechanism.     

Preparation and Evaluation of Sustained release Indomethacin Nonpareil Seeds

A controlled release oral drug delivery system of Indomethacin was developed using nonpareil seeds as a matrix system. These seeds were coated with different concentrations of drug release controlling materials viz Eudragit RL100 and Eudragit RS100, and bees wax. The particle size of the seeds and the concentration as well as the type of the drug release controlling Eudragits has a pronounced effect on the release rate profile of Indomethacin. All types of formulations showed release rate pattern which can be described by both first-order and diffusion controlled mechanism.     

Preparation and in Vitro Evaluation of Controlled Release Dosage form of Indomethacin

A controlled release oral drug delivery system of Indomethacin was developed using gelatin as the matrix system, which was rigidized with different concentrations of formalin, without using alcohol. The proportion of drug and gelatin as well as the concentration of formalin had the pronounced effect on the Indomethacin release rate and the patterns of which depicted that they correlated with Lang primary requirements for drug release from controlled release dosage forms. All the types of formulations showed release rate patterns that could best be described by First Order Kinetics, indicating that First Order release was mainly operative.     

Preparation and in Vitro Evaluation of Controlled Release Dosage form of Indomethacin

Abstract

A controlled release oral drug delivery system of Indomethacin was developed using gelatin as the matrix system, which was rigidized with different concentrations of formalin, without using alcohol. The proportion of drug and gelatin as well as the concentration of formalin had the pronounced effect on the Indomethacin release rate and the patterns of which depicted that they correlated with Lang primary requirements for drug release from controlled release dosage forms. All the types of formulations showed release rate patterns that could best be described by First Order Kinetics, indicating that First Order release was mainly operative.     

Preparation and Evaluation of Fast-Disintegrating Effervescent Tablets of Glibenclamide

Fast-dissolving effervescent tablets (FETs) were prepared by the modification of nonreactive liquid-based wet granulation technique. Effervescent systems are not stable in the presence of trace amount of moisture, and elimination or inactivation of free water is the key to stability apart from manufacturing in controlled humidity environment. Our main objective of the project was to develop FETs of glibenclamide based on highly plastic granules that can be compressed at low pressure to form fast-melting pharmaceutical tablets. In this study, we have screened various acid and carbonate sources for the effervescent system. Citric acid was coated with plastic materials such as polyethylene glycol (PEG), which provide a physical barrier to the reaction. The inherent hygroscopic nature of PEG could decrease the affinity for moisture of effervescent mixtures and can provide a stabilizing effect. Sodium bicarbonate was blended with sugar alcohol like mannitol, which would give a protective coating. PEG 1000 melts at body temperature (～37°C) and thereby does not delay the reaction between the acid source and base. The present formulation using citric acid–sodium bicarbonate and citric acid–sodium glycine carbonate tablet with PEG and mannitol was found to have better reaction properties and reaction stability than does the standard citric acid–sodium bicarbonate tablet. FETs of glibenclamide might aid in dissolution due to increase in microenvironmental pH around the granules and saliva. Sensory study on disintegration time and mouth feel attributes ranked the present formulation based on grittiness, chalkiness, and overall preference as best.     

Preparation and Evaluation of Directly Compressed Medazepam Hydrochloride Tablets

Medazepam, the well known benzodiazepine derivative used as a transquillizer and in alcohol withdrawal, was prepared in directly compressed tablets. The directly compressible vehicles which were used. singly or in binary blends 1:1, were Avicel, Lactose, STA-Rx 1500 Emcompress and the recently introduced vehicle compactrol. It was found that Avicel and Emcompress represent the most suitable single vehicles used for the preparation of Medazepam hydrochloride tablets. In case of binary blends it was found that the best quality batches were prepared using Avicel Emcompress blend 1:1. Physical characteristics including uniformity of weight, thickness, hardness, friability were investigated for the prepared batches. The effect of directly compressible vehicle variation on the uniformity of drug content and the dissolution rates of Medazepam hydrochloride tablets was also studied.     

Influence of Sodium Lauryl Sulphate on Indomethacin Release Pattern from Zinc-Indcmethacin Complex and Indomethacin Capsules

Abstract

A study was carried out to investigate the drug release pattern from zinc-indomethacin capsules with sodium lauryl sulphate (0. 25-1. 0% by weight of indomethacin) using the rotating basket method (USP XXI). The Drug release data failed to follow commonly used kinetic models that could explain the release pattern. Hence, the results were interpreted on the basis of bi-exponential, first-order kinetic model and found a good correlation between calculated and observed values. It showed that sodium lauryl sulphate enhanced both the faster and slower rate constants of the bi-exponential, first-order kinetic model and the percentage of the drug dissolved according to the faster process was increased. Indomethacin capsules with sodium lauryl sulphate showed also a similar release pattern.     

Chitosan and Sodium Sulfate as Excipients in the Preparation of Prolonged Release Theophylline Tablets

The major objectives of this study were to monitor the effect of cross-linking of cationic chitosan in acidic media with sulfate anion during granules preparation by wet granulation method prior to tableting using theophylline (TPH) as a model drug. The prepared granules and the compressed tablets were subjected to in vitro evaluation. The properties of the prepared matrix granules and the compressed tablets were dependent on chitosan:sodium sulfate weight ratios, chitosan content, and molecular weight of chitosan. The prepared granules of all batches showed excellent to passable flowability and were suitable for compression into tablets. Most of the granules were hard and expected to withstand handling during the subsequent compression into tablets. Granules with high friabilities were only those prepared with a high amount of sodium sulfate or low amount of chitosan. Compression of granule batches yield nondisintegrating tablets that showed a decrease in tensile strength with the increase of sodium sulfate content at high chitosan:sodium sulfate weight ratio or with decrease of chitosan content. On the other hand, friability of tablets was increased in the presence of an excessive amount of sodium sulfate and low chitosan content as observed with granules. Slow TPH release from the formulated tablets was achieved at 1:0.5 and 1:1 chitosan:sodium sulfate weight ratios where all or most of the cationic chitosan and sulfate anions were used in a cross-linking reaction during wet granulation. Ratios of 1:2 and 1:3 showed fast drug release, which support the hypothesis that excessive unreacted water-soluble sodium sulfate might increase the porosity of the nondesintegrating tablets during dissolution. Slow drug release was also obtained with high molecular weight chitosan, whereas changing the hardness of the tablets did not significantly change the release profile of the drug as long as the tablets are intact during dissolution. Furthermore, slow drug release was observed as the total amount of chitosan was increased in the formulated tablets. A comparative in vivo study between the chosen formulated tablets (1:1 chitosan:sodium sulfate ratio that contains 10% high molecular weight chitosan) and the commercial Quibron® tablets indicated prolonged appearance of the drug in dogs' plasma for both formulations with no significant differences (p > 0.05) in rate and extent of drug absorption. The formulated tablets showed 103.16% bioavailability relative to that of the commercial tablets.     

Preparation and In-Vitro Evaluation of Powder Solution Tablets of Valproic Acid

A tablet dosage form of liquid valproic acid (VPA) was formulated using powder solution technology as an alternative to the manufacturing of soft elastic gelatin capsules (SEGs). Mixing of liquid VPA with suitable adsorbents followed by blending with other excipients resulted in a non-adherent, free flowing powder. Tableting was achieved through standard direct compression. The tablets were acceptable in terms of physical properties. Film coated tablets (FCTs) and sugar coated tablets (SCTs) were also prepared. The in-vitro dissolution rates of these VPA tablets were significantly greater than that of a marketed SEG product. There was no significant change in the dissolution rates of the plain and FCTs after storage under accelerated stability conditions. Powder solution technology was a viable alternative to the commercial preparation of SEGs.     

Preparation and In-Vitro Evaluation of Prolonged Release Tablets of Pheniramine Aminosalicylate

Prolonged release tablets of pheniramine aminosalicylate were prepared from co-precipitates of the drug in different types of Eudragit. The hardness of the tablet had a pronounced effect on the release rate of the drug. Tablets (500 mg, hardness 13 kg) and 375 mg tablets (hardness 6.5 kg) prepared from the co-precipitates containing 15% of the drug in Eudragit L 100, and 20% of the drug in Eudragit S 100 respectively, showed release rate patterns that were in agreement with Lang primary requirements for drug release from sustained release tablets.

Tablets (500 mg) prepared from the co-precipitates containing 15% of the drug in Eudragit L 100 or Eudragit S 100 and 375 mg tablets containing 20% of the drug in Eudragit S 100 showed release rate patterns that were best described by Higuchi equation, indicating that a diffusion controlled mechanism was mainly operative.     

Preparation and In-Vitro Evaluation of Powder Solution Tablets of Valproic Acid

Abstract

A tablet dosage form of liquid valproic acid (VPA) was formulated using powder solution technology as an alternative to the manufacturing of soft elastic gelatin capsules (SEGs). Mixing of liquid VPA with suitable adsorbents followed by blending with other excipients resulted in a non-adherent, free flowing powder. Tableting was achieved through standard direct compression. The tablets were acceptable in terms of physical properties. Film coated tablets (FCTs) and sugar coated tablets (SCTs) were also prepared. The in-vitro dissolution rates of these VPA tablets were significantly greater than that of a marketed SEG product. There was no significant change in the dissolution rates of the plain and FCTs after storage under accelerated stability conditions. Powder solution technology was a viable alternative to the commercial preparation of SEGs.     

Preparation and Evaluation of a Sustained-Release Formulation of Nifedipine HPMC Tablets

A nifedipine (NF) polyethylene glycol (PEG) solid dispersion was prepared. Using this solid dispersion, NF hydroxypropylmethylcellulose (HPMC) matrix tablets were prepared. Both the high-viscosity grade HPMC (Methocel K15M) and low-viscosity grade HPMC (Methocel K100) were applied in the tablets to form the matrix. The dissolution and absorption of NF from the tablet were evaluated as a formulation that had a sustained release over 24 hr. The Hixson-Crowell equation and Higuchi equation were used to investigate the dissolution mechanism, and the erosion and diffusion codependent mechanism was established. Adalat GITS 30 was used as a reference dosage form. Each beagle dog was also administered an intravenous injection to obtain the pharmacokinetics parameters. The Loo-Riegelman method was applied to study the in vitro/in vivo correlation of the tested tablets and Adalat GITS 30, and significant correlation was proved. Absolute bioavailability and comparative bioavailability of the tested tablet were studied. The results indicated that the NF HPMC tablet could be an ideal 24-hr sustained-release formulation.     

Evaluation of Pharmaceutical Quality of Phenytoin Sodium Capsules and Tablets from Multinational Markets*

This report presents the results obtained in the above-titled study for the quality of phenytoin sodium tablets and capsules (100 mg) available in the markets of various countries worldwide, especially members of the Official Laboratories and Medicines Control Services (OLMCS) section of FIP. The products were analyzed following a common protocol based on the methodologies described in the European (Ph.Eur.), British (BP), and/or United States Pharmacopeia (USP). Pharmacotechnic tests (uniformity of weight, disintegration), identification, assay, and dissolution of active ingredient were preformed by 23 laboratories from 20 countries that submitted data from 52 samples representing 37 products available in the local markets. Innovator products from 17 countries were analyzed in LEF. Most products tested &Wed the pharmacopeial requirements concerning uniformity of weight, disintegration, identity, and content. Marked differences were recorded in respect of in vitro dissolution behavior. This applies not only to the products of different brands but also among lots of the same brand name produced in difei-ent countries     

Evaluation of Xanthan Gum in the Preparation of Sustained Release Matrix Tablets

The objective of this study was to evaluate xanthan gum as a matrix former for the preparation of sustained release tablets. Preliminary experiments indicated that a fine particle sue of xanthan gum produced the slowest and most reproducible release profiles. Based on single surface experiments and tablet erosion studies, it was concluded that release of a soluble drug (chlorpheniramine maleate) and an insoluble drug (theophylline) from tablets containing low concentraions of xanthan gum was mainly via diffusion and erosion, respectively. Drug release from tablets containing xanthan gum was slightly faster in acidic media due to more rapid initial surface erosion than at higher pH. After hydration of the gum, drug release was essentially pH-independent. The amount released was directly proportional to the loading dose of drug and inversely proportional to gum concentration in tablets. Release profiles of chlorpheniramine maleate and theophylline remained unchanged after three months storage of the tablets at 40°C/80% RH and 40°C. Model tablets containing 5% xanthan gum exhibited release profiles similar to tablets containing 15% hydroxypropyl methylcellulose.