配制200毫克剂量的氢氯噻嗪亲水性缓释骨架片。30%ww.PDF

Barrier Membrane Coating of Hydrophilic Matrices: A Strategy to Reduce Drug Release Variability and Possible Food Effect Raxit Y. Mehta, Sandip B. Tiwari, Thomas P. Farrell and Ali R. Rajabi-Siahboomi Poster Reprint CRS 2011 Abstract Summary Extended release, hydrophilic matrix tablets of hydrochlorothiazide (HCTZ) at 200 mg dose were formulated using low viscosity hypromellose (hydroxypropyl methylcellulose, HPMC) as a rate controlling polymer at 30% w/w level. In vitro dissolution studies of this formulation indicated variability in drug release rate at agitation speeds of 50, 100 and 150 rpm (ƒ250). Such an in vitro behavior may indicate a possible food effect. Application of a barrier membrane (BM) coating with Surelease® aqueous ethylcellulose dispersion (E-7-19010) including a pore-former (Opadry® complete film coating system) resulted in consistent and robust drug release profiles at agitation speeds of 50, 100 and 150 rpm (ƒ 60). Near zero order drug release profiles were obtained. Coating weight gain and level of pore 2 former in the BM coating were found to be critical in achieving robust and stable drug release profiles. Introduction Hydrophilic matrix systems are most popular among different technologies used in the manufacture of oral controlled release systems because of the simplicity of formulation, ease of manufacturing, low cost, regulatory acceptance, and applicability to drugs with wide range of dose and solubility. Low viscosity hypromellose (METHOCEL™ K100LV Premium CR) is generally recommended for formulating matrices of low solubility APIs, for example BCS Class II drugs. As the release of such low solubility APIs from the matrix predominantly occurs via an erosion mechanism, control over the matrix erosion is necessary to achieve con