Influence of Formulation Factors and Compression Force on Release Profile of Sustained Release Metoprolol Tablets using Compritol (R) 888ATO as Lipid Excipient

摘要

Tablets containing metoprolol succinate and Compritol (R) 888ATO in the ratio of 1: 2 yielded the desired sustained release profile in phosphate buffer pH 6.8 when evaluated using USP type II paddle apparatus and was selected as the optimized formulation. Robustness of optimized formulation was assessed by studying the effect of factors like varying source of metoprolol succinate and Compritol (R) 888ATO, compression force and hydroalcoholic dissolution medium on the release profile. No significant difference (P>0.05) in release profile was observed when metoprolol succinate from three different sources and Compritol (R) 888ATO from two different batches were used. Release profile of sustained release tablets of metoprolol succinate in media containing various concentrations of ethanol was comparable with media devoid of ethanol as evaluated by f2 test. This indicated that release profile of sustained release tablets of metoprolol succinate was reliable with no significant change due to variation in source of active pharmaceutical ingredient, particularly due to particle size distribution. Sustained release tablets of metoprolol succinate yielded release pattern within specifications irrespective of presence or absence of ethanol in the medium indicating that release properties of Compritol (R) 888ATO matrix are not affected by ethanol. Tablets compressed at compression force of <100 kg/cm(2) exhibited low hardness with total porosity of 15.39% and significantly increased (P<0.05) metoprolol succinate release as compared to tablets compressed at 2000 kg/cm(2) with 6.90% of total porosity revealing influence of compression force. Compritol (R) 888ATO holds great potential in providing reliable and controlled release profile of highly water soluble metoprolol succinate.