Development of In Situ Gelling Formulations for Per-Oral Sustained Delivery of Dextromethorphan

MastersPurpose: The aim of our work was to develop a modified in situ gelling oral liquid sustained release formulations of dextromethorphan using alginate based systems. These systems were further reinforced to provide sustained release behavior over different sites of the GIT through: A. Reinforcing the gel structure through incorporation of another polymer with sodium alginate, namely chitosan. B. Controlling the solubility of the drug through formation of solid dispersions of DM with Eudragit S 100 in different ratios, before dispersing the resultant microparticles in the alginate vehicle. Results: The alginate concentration of 2 % w/v (the most optimized vehicle) showed excellent flow properties and high gelling capacity in the physiological conditions. However, dose dumping is still a problem with all the forumlations. Alginate/Chitosan in situ gelling systems showed a pseudoplastic flow patterns. The in vitro release investigations revealed that the alginate/chitosan dispersion of concentration (2:1.5 % w/w alginate: chitosan) was found to be the most efficient one with release efficiency 32.76 % after 8 hr. The interaction studies revealed the occurrence of interaction between DM & Eudragit S 100. The in vitro release behavior of the formulations showed a sustained release effect & similarity with the marketed product. Conclusion: Improvement of the gelation & in vitro release characteristics of the alginate/chitosan mixture is possibly not only a result of a combination of two in situ gelling ion responsive polymers, but may also be due to a synergistic interaction between the two polymers resulting in the formation of a firm gel structure capable of holding the drug for a period of time up to 8 hr. The sustained release properties have been improved by the combined effect of the in situ gelation behavior of alginate solution & the partial coating of DM microparticles with ES 100 in the formulation