1 To Study the Effect of Hydroalcoholic Dissolution Media for Integrity of Sustained Release Polymer

Abstract : In July 2005, the FDA issued an alert for healthcare professionals regarding dissolution media effects on drug release from a SR dosage form not involving a hydrophilic matrix, i.e., alcohol-Palladone interaction1. Hence, the aim of present works was to check the effect of Hydro alcoholic dissolution media in sustained release polymer and investigate the influence of hydro-alcoholic media on drug release for metoprolol Succinate sustained release tablets. Metoprolol succinate is a drug used for Hypertension and it is suitable drug candidate for extended release due to its short Half-life. Combination of HPMC K4M and HPMC K100M, Carbopol 934 P, Chitosan, HPMC K100 M: Ethyl Cellulose (4:1), Sodium-Carboxyl Methyl Cellulose were used as a polymer matrix to control the release of Metoprolol succinate up to 12 hrs. The Sustained release tablets of Metoprolol succinate were prepared by Wet granulation method. All the tablets were evaluated for the Pre-compression and post Compression Parameter. In-vitro dissolution study was done in Normal Dissolution Media, Phosphate Buffer pH 6.8 and also in 10 %, 20 %, 30 % and 40% v/v ethanol solutions for up to 12 hrs. All HPMC, Chitosan, Sodium-CMC preparation did not fail in hydro-alcoholic media, while Carbopol 934 P preparation show highest differences compare to all other. The highest dissolution was found to be more than 80 % in 12 hours for 40 % v/v ethanol solution in Carbopol 934 P ,which was not comply with standard range of drug release by USFDA and show dose dumping of Formulation. Kinetic model application confirmed that the release of Metoprolol succinate follows zero order as well as Korsmeyer-Peppas model. From these studies it was concluded that Carbopol 934 P formulation indicated highest signs of a potential dose dumping compare with other formulation.

Keyword : Dose dumping, Sustained Release Polymer, Hydroalcoholic Dissolution Media.