methylcellulose and pelanserin

Pelanserin is a weakly basic experimental drug with a short half-life and a prolonged release formulation was developed using hydroxypropyl methylcellulose (HPMC) and citric acid to set up a system bringing about gradual release of this drug. For this purpose powder mixtures were wet granulated with water and compressed with a hydraulic press at 55 MPa. Dissolution studies were made using 900 ml HCl 0.1 N, the first 3 h, and phosphate buffer pH 7.4, h 3-8. Dissolution curves were described by M(t)/M(inf)=kt(n), applied separately for each dissolution medium. The dissolution mechanism involved a coupled diffusion/relaxation with a trend favoring the diffusion mechanism with increasing citric acid concentrations. Increasing concentrations of citric acid produced increasing values of the kinetic constants, in a cubic relationship. Higher HPMC proportions produced slower dissolution rates but with a citric acid compensating more clearly a decreased solubility of pelanserin at pH 7.4. Individually calculated dissolution curves showed experimental 8 h pelanserin dissolution in a range of 65-99% for matrices with 100 mg HPMC/tab., while those with 200 mg HPMC/tab. were in the range 57-73%.

Topics: Antihypertensive Agents; Citric Acid; Delayed-Action Preparations; Drug Carriers; Hydrogen-Ion Concentration; Lactose; Methylcellulose; Oxazines; Quinazolines; Regression Analysis; Solubility