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The effects of selected superdisintegrants on the dissolution behavior of several cationic drugs with varying water solubility were evaluated. All formulations were made with fixed disintegrant concentration and equal drug load using a model formulation. Tablets were made by direct compression and were compressed to equal hardness. Dissolution studies were carried out in dissolution media specified in the compendium (USP) or in media recommended by the U.S. Food and Drug Administration (FDA) for the respective actives. The effect of media pH on the dissolution of drugs was also evaluated.The use of crospovidone significantly improved the dissolution of the cationic drugs in the model formulation when compared with the other superdisintegrants studied. The compendial or the FDA recommended media, in most cases, was able to discriminate among the tablets containing different superdisintegrants.Crospovidone can be effectively used as a tablet disintegrant to improve the dissolution of either soluble or poorly soluble cationic drugs.

Metformin microspheres with sodium alginate alone and in combination with gellan were prepared using an emulsion-cross linking method. The prepared microspheres were evaluated for their physico-chemical characteristics like particle size, morphology using SEM, incorporation efficiency, equilibrium water content (swelling) and in vitro drug release. The effect of various formulation variables like polymer concentration (sodium alginate; and proportion of gellan in microspheres prepared by a combination of sodium alginate and gellan), drug loading, crosslinking agent concentration and cross-linking time on the in vitro dissolution of the prepared microspheres were evaluated. The results showed that both the particle size and the incorporation efficiency were proportional to the polymer concentration. In case of microspheres containing both sodium alginate and gellan, the mean diameter and the incorporation efficiency were higher than the corresponding microspheres containing only alginate, both increasing with an increase in proportion of gellan. The prepared microspheres were found to be discrete and spherical in shape and were successful in sustaining the drug release for 8 hours. Incorporation of gellan caused a significant decrease in drug release. The release followed a biphasic profile, in all cases, characterized by an initial phase of moderate drug release followed by a phase of higher release. Further, the kinetic treatment of the dissolution data revealed the prevalence of matrix diffusion kinetics.

Marshall and Warren discovered Helicobacter pylori, which is now recognized as a major gastric pathogen with worldwide distribution. H. pylori is a prevalent human-specific pathogen and a causative agent in chronic active gastritis, duodenal ulcers, and gastric adenocarcinoma.1-3) Although the microorganism is susceptible to many antimicrobial agents in vitro, clinical trials with a single antimicrobial agent have resulted in a low eradication rate of H. pylori. 3,4) This is because of the low concentration of the antibiotic reaching the bacteria under the mucosa; instability of the drug in the low pH of gastric fluid, and the short residence time of the antibiotic in the stomach. 5) Therefore, eradicating H. pylori is a prerequisite for curing a gastric or peptic ulcer and preventing a recurrence.3) Triple therapy consisting of combined use of antibiotics, such as amoxicillin, clarithromycin/metronidazole, and a proton pump inhibitor gives a high eradication rate, and is now frequently used for clinical treatment of H. pylori associated gastroduodenal disease. However, eradication is not always successful and harmful side effects, cost of therapy, and the lack of willingness to take many different drug products are the major drawbacks of the therapy. 5,6) Other than the multi-antibiotic therapy, other strategies that can completely eradicate H. pylori from the stomach have been examined. One way to improve the efficacy in eradicating the infection is to deliver the antibiotic locally in the stomach 5,7) by increasing residence time of antibiotics at infected site. Another way is to improve the stability of antibiotics in gastric environment. The antibiotics with better stability and longer residence time will allow more of the antibiotic to penetrate through the gastric mucus layer to act effectively on H. pylori. Gastroretentive drug delivery systems like floating and bioadhesive system would improve the therapeutic effect of antimicrobial drugs.8) Research into gastroretentive drug delivery systems has resulted in the development of several approaches including the use of tabletsin-capsule, 9) floating systems 10,11) in situ gelling systems, 12,13) mucoadhesive tablet, pH-sensitive excipient composition mucoadhesive microspheres 14,15) etc., which were able to reside in the gastrointestinal tract for an extended period of time for a more effective H. pylori eradication.Mucoadhesive drug carriers may prolong the residence time in the gastrointestinal tract (GI) tract because they can adhere to the mucus surface, resulting in an effective localized drug concentration.10,15) Among several mucoadhesive polymers, Carbopol usually has strong mucoadhesive properties and is known to be biocompatible and nontoxic. Multiple unit gastroretentive dosage forms, like floating microspheres or microcapsules, can be distributed widely throughout the GI tract, providing the possibility of achieving a longer lasting and more reliable release of drugs. 16,17) Clarithromycin is a macrolide, orally absorbed, broad-spectrum antibio...

Periodontal pocket inserts of niridazole (NZ) made with Resomer(R) (grades RG 503H and RG858, designated as RH and RG, respectively) were studied. Various formulation variables were evaluated to obtain a biodegradable delivery systems showing device degradation and drug depletion parallel to each other in vitro. Drug release from the prepared inserts was evaluated using a static dissolution setup (for 1 month). Incorporation of 3 parts of RG in 1 part of RH inserts caused a 50% decrease in the initial release rate. The RH-NZ inserts showed a spurt in release around the 10th day of the study, which coincided with the decrease in device weight, suggesting onset of device degradation. Pilot-scale clinical trials in 12 patients indicated improvements in clinical indices from the baseline values. The average pocket depth was reduced significantly (alpha = 0.05) from 6.34 +/- 1.86 mm at baseline to 5.94 +/- 0.28 mm after 28 days of treatment.

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Lamotrigine is a BCS class II drug with pH dependent solubility. The bilayered gastric mucoadhesive tablets of lamotrigine were designed such that the drug and controlled release polymers were incorporated in the upper layer and the lower layer had the mucoadhesive polymers. The major ingredients selected for the upper layer were the drug and control release polymer (either HPMC K15M or polyox) while the lower MA layer predominantly comprised of Carbopol 974P. A 2(3) full factorial design was constructed for this study and the tablets were optimized for parameters like tablet size, shape, ex vivo mucoadhesive properties and unidirectional drug release. Oval tablets with an average size of 14 mm diameter were set optimum. Maximum mucoadhesive bond strength of 79.3 ± 0.91 * 10(3) dyn/cm(2) was achieved with carbopol when used in combination with a synergistic resin polymer. All the tested formulations presented a mucoadhesion time of greater than 12 h. The incorporation of methacrylic polymers in the lower layer ensured unidirectional drug release from the bilayered tablets. The unidirectional drug release was confirmed after comparing the dissolution results of paddle method with those of a modified basket method. Model independent similarity and dissimilarity factor methods were used for the comparison of dissolution results. Controlled drug release profiles with zero order kinetics were obtained with polyox and HPMC K15M which reported t 90% at 6th and 12th hours, respectively. The "n" value with polyox was 0.992 and that with HPMC K15M was 0.946 indicating an approximate case II transport. These two formulations showed the potential for oral administration of lamotrigine as bilayered gastric mucoadhesive tablets by yielding highest similarity factor values, 96.06 and 92.47, respectively, between the paddle and modified basket method dissolution release profiles apart from reporting the best tablet physical properties and maximum mucoadhesive strength.