高剂量易溶于水的药物,酒石酸美托洛尔骨架的膜控包衣.PDFVIP

Barrier Membrane Coating of Hydrophilic Matrices of a Very Soluble Drug, Metoprolol Tartrate at High Dose: A Strategy to Eliminate the Initial Burst Release Poster Reprint Raxit Y. Mehta, Shahrzad Missaghi, Thomas P. Farrell and Ali R. Rajabi-Siahboomi CRS 2012 Abstract Summary Extended release hydrophilic matrix tablets of metoprolol tartrate were formulated using high viscosity hypromellose (METHOCEL™ premium cellulose ethers, K15M) as a rate-limiting polymer. In vitro dissolution studies of the tablets indicated initial burst, followed by a sustained drug release pattern. Application of barrier membrane (BM) coating, using aqueous ethylcellulose dispersion (Surelease® aqueous ethylcellulose dispersion, E-7-19010) with a pore- former (Opadry® complete film coating system), resulted in elimination of the burst effect, followed by near zero order release. The findings of the study indicated robust and consistent drug release when the BM coated matrices were exposed to bio-relevant media and different agitation rates. Introduction Hydrophilic matrix systems are the most popular technology used in oral extended release drug delivery. For the purpose of achieving extended release of a high dose and highly water soluble drug, such as metoprolol tartrate, rapid hydration and strong gel layer formation of the rate controlling polymer are essential. Generally a high viscosity grade of hypromellose is used. However, the highly soluble drug available at and adjacent to the surface of the matrix dissolves immediately upon contact with the dissolution media and released, prior to formation of the gel layer. This gives rise to an initial burst release followed by controlled release of the drug.1