TY - JOUR
T1 - Influence of admixed citric acid on the release profile of pelanserin hydrochloride from HPMC matrix tablets
AU - Espinoza, Rogelio
AU - Hong, Enrique
AU - Villafuerte, Leopoldo
PY - 2000/5/25
Y1 - 2000/5/25
N2 - 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%. Copyright (C) 2000 Elsevier Science B.V.
AB - 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%. Copyright (C) 2000 Elsevier Science B.V.
KW - Citric acid
KW - HPMC, Sustained release
KW - Pelanserin
KW - Release mechanism
KW - pH effect
UR - http://www.scopus.com/inward/record.url?scp=0034713306&partnerID=8YFLogxK
U2 - 10.1016/S0378-5173(00)00406-3
DO - 10.1016/S0378-5173(00)00406-3
M3 - Artículo
SN - 0378-5173
VL - 201
SP - 165
EP - 173
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 2
ER -