Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100

• Published in: Acta Pharmaceutica 2014-03, Vol.64 (1), p.29-44
• Main Authors: Maghraby, Gamal Mohamed El, Elzayat, Ehab Mostafa, Alanazi, Fars Kaed
• Format: Article
• Language: English
• Subjects: alginate gels; Alginates - chemistry; Calorimetry - methods; Chemical Precipitation; Chemistry, Pharmaceutical; Delayed-Action Preparations - chemistry; dextromethorphan; Dextromethorphan - chemistry; Gels; Glucuronic Acid - chemistry; Hexuronic Acids - chemistry; in situ gelling; Polymethacrylic Acids - chemistry; solid dispersion; X-Ray Diffraction - methods
• ISSN: 1330-0075; 1846-9558
• DOI: 10.2478/acph-2014-0002

Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels