Influence of admixed 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 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%.
Espinoza
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R
Department of Pharmacy, Escuela Nacional de Ciencias Biológicas, National Polytechnic Institute of Mexico, Carpio y Plan de Ayala, Col. P. Elías Calles, C.P. 11340, D.F., Mexico, Mexico.
Hong
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E
Villafuerte
L
L
D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry; D019343:Citric Acid / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D010078:Oxazines; D011799:Quinazolines / Q000008:administration & dosage* / Q000737:chemistry; D012044:Regression Analysis; D012995:Solubility
D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010078:Oxazines; D011799:Quinazolines; D019343:Citric Acid; C043157:pelanserin; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose