Release Adjustment of Two Drugs with Different Solubility Combined in a Matrix Tablet.

The objective of this study was to modify the release of two drugs having different solubility in a combined matrix tablet as a fixed-dose combination for extended release. Propranolol HCl (freely soluble) and carbamazepine (very slightly soluble) were used as model drugs, water-soluble hydroxypropyl methylcellulose (HPMC) and water-insoluble ethylcellulose (EC) were used as matrix-forming polymers. Tablets were prepared by direct compression of powder blends, or propranolol HCl was first granulated with one of the matrix-forming polymers (1:1) followed by compression with carbamazepine and matrix former. Propranolol HCl release from directly compressed tablets was faster than carbamazepine because of its higher solubility. The release of both drugs was fast when HPMC-propranolol HCl granules were compressed with carbamazepine into EC matrix tablet. Conversely, the release of both drugs was decreased when HPMC-propranolol HCl granules and carbamazepine were compressed into HPMC matrices. The desired release of both drugs was approached when EC-propranolol HCl granules were compressed with carbamazepine into HPMC matrix. Erosion of the HPMC matrix and, therefore, drug release were adjusted by varying the molecular weight of HPMC. A burst release of propranolol HCl decreased when it was granulated with EC in a fluidized bed coater followed by compression with carbamazepine into HPMC matrix.