TY - JOUR
T1 - Influence of enteric citric acid on the release profile of 4-aminopyridine from HPMC matrix tablets
AU - Martínez González, Ilona
AU - Villafuerte Robles, Leopoldo
PY - 2003/1/30
Y1 - 2003/1/30
N2 - A weakly basic experimental drug, 4-aminopyridine (4-AP), was taken as a model to study the influence of enteric citric acid (ECA) on the release profile from hydroxypropyl methylcellulose (HPMC) matrices, to set up a system bringing about gradual release of the 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 first 900 ml HCl 0.1 N, and then phosphate buffer pH 7.4. Dissolution curves were described by Mt/Minf=ktn. As physically expected, increasing proportions (2-9%) of the in acid insoluble ECA decreased the release rate. In an acid medium, ECA acts as a physical barrier obstructing the diffusion path, dissolving after the pH change to 7.4. Both circumstances flattening the release profile. Apparent zero order release was observed at ECA concentrations of about 10%. The presence of ECA compensates the effect of decreased solubility of 4-AP at pH 7.4. Unexpectedly, higher ECA proportions (10-50%) act increasing the dissolution rate. This is attributed to a void space formation around the insoluble ECA, after HPMC hydration, which percolates after a critical ECA proportion of approximately 10%. Moreover, decreasing release constant values (k) show a logarithmic relationship with increasing values of the exponent (n). This indicates that an apparent zero-order release can be obtained at a given release constant.
AB - A weakly basic experimental drug, 4-aminopyridine (4-AP), was taken as a model to study the influence of enteric citric acid (ECA) on the release profile from hydroxypropyl methylcellulose (HPMC) matrices, to set up a system bringing about gradual release of the 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 first 900 ml HCl 0.1 N, and then phosphate buffer pH 7.4. Dissolution curves were described by Mt/Minf=ktn. As physically expected, increasing proportions (2-9%) of the in acid insoluble ECA decreased the release rate. In an acid medium, ECA acts as a physical barrier obstructing the diffusion path, dissolving after the pH change to 7.4. Both circumstances flattening the release profile. Apparent zero order release was observed at ECA concentrations of about 10%. The presence of ECA compensates the effect of decreased solubility of 4-AP at pH 7.4. Unexpectedly, higher ECA proportions (10-50%) act increasing the dissolution rate. This is attributed to a void space formation around the insoluble ECA, after HPMC hydration, which percolates after a critical ECA proportion of approximately 10%. Moreover, decreasing release constant values (k) show a logarithmic relationship with increasing values of the exponent (n). This indicates that an apparent zero-order release can be obtained at a given release constant.
KW - 4-Aminopyridine
KW - Enteric citric acid
KW - HPMC
KW - Release mechanism
KW - pH effect
UR - http://www.scopus.com/inward/record.url?scp=0037472340&partnerID=8YFLogxK
U2 - 10.1016/S0378-5173(02)00598-7
DO - 10.1016/S0378-5173(02)00598-7
M3 - Artículo
SN - 0378-5173
VL - 251
SP - 183
EP - 193
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -