Influence of admired citric acid on the release profile of pelanserin hydrochloride from HPMC matrix tablets

Pelanserin is a weakly basic experimental drug with a short half-life and a prolonged release formulation was developed using hydroxypropyl methylcell ulose (HPMC) and citric acid to set up a system bringing about gradual rele ase 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 mi 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 s eparately 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 c itric 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 pel anserin at pH 7.4. Individually calculated dissolution curves showed experi mental 8 h pelanserin dissolution in a ran ge of 65-99% for matrices with 1 00 mg HPMC/tab., while those with 200 mg HPMC/tab. were in the range 57-73% . (C) 2000 Elsevier Science B.V. All rights reserved.