Captopril gastrointestinal therapeutic system coated with cellulose acetate pseudolatex: evaluation of main effects of several formulation variables

Maintenance of constant drug levels in the body for those drugs that are us ed in management of hypertension is extremely beneficial. This can be succe ssfully achieved by delivering the antihypertensives as osmotically-control led drug-delivery system that essentially eliminates the influence of pH on the drug release. The main objective of this study was to evaluate the mai n effects of the formulation variables on the release of captopril from osm otically-controlled drug-delivery system coated with a custom-made cellulos e acetate (CA) pseudolatex reported earlier. A secondary objective was to i dentify a suitable antioxidant for incorporating in the formulation as the drug undergoes metal-catalyzed oxidative degradation. The drug showed good stability (greater than or equal to 90% intact captopril) in solution in th e presence of ascorbic acid for a period of 48 h. A seven-factor, 12-run Pl ackett-Burman screening design was employed to study the main effects of am ounts of Polyox(R) N10 and N80, Carbopol(R) 934P and 974P, sodium chloride, orifice size, and % coating weight gain. The response variable was cumulat ive percent of drug released in 12 h, Y-3, with constraints on lag time Y-1 and time for 50% drug released Y-2. Quantitative evaluation of the screeni ng design variables revealed that Polyox(R) N10, Carbopol 974P, and % coati ng weight gain had a greater influence on the drug release than the rest of the factors. The main effects decreased in the order: Polyox(R) N10 (-8.07 ) = % Coating weight gain (-8.07) > Carbopol(R) 974P (6.83) > Carbopol(R) 9 34P (-5.3) > Polyox(R) NgO (5) > orifice size (2.6) > amount of sodium chlo ride (1.97). (C) 2000 Elsevier Science B.V. All rights reserved.