Title: Formulation, in vitro characterization and optimization of taste masked orally disintegrating co-trimoxazole tablet by direct compression

Abstract

Background: Orally disintegrating tablet (ODT) is a dosage form that overcomes the problem of swallowing which is very prevalent. Co-trimoxazole (CTX) is given for patients with HIV as prophylaxis of opportunistic infection. Esophageal candidiasis, one of AIDS defining opportunistic infection (OI), affects up to 1 out 5 people with AIDS. This OI is manifested by painful swallowing. Therefore, CTX ODT offers the advantage of easy swallowing thereby improving patient compliance. Objective: The objective of this study was to formulate, characterize & optimize CTX ODT. Method: Co-trimoxazole ODTs were prepared by direct compression. Two taste masking techniques were employed, addition of sweetening agent, and solid dispersion by using Eudragit E-100 at different ratios (1:1, 1:2 and 1:3). Taste masking was determined by comparing taste threshold value and in vitro drug release. Preliminary study was used to investigate the effect of three independent variables on Disintegration time, friability and wetting time (WT). From the preliminary study, the factors that were found significant were further optimized using central composite design (CCD). Design-Expert 8.0.7.1 software was employed to carry out the experimental design. Result: The bitterness threshold concentration of Trimethoprim was found to be 150 μg/ml and the in vitro drug release of the three batches of drug to polymer ratio (F1:1, 1:2 and 1:3) was 2.80±0.05, 2.77±0.00 and 2.63±0.00 respectively. From the optimization study, the optimal concentration for the super Disintegrant was 8.60% w/w and a CF of 11.25 KN which gave a rapid disintegration and WT of 13.79 and 23.19 seconds respectively and a friability of 0.666%. Conclusion: In this study, co-trimoxazole ODT was formulated successfully. Optimization of the response variables was possible and the predicted optimal conditions were confirmed experimentally and were found to be in good agreement within 5% of the predicted responses. The successful formulation of CTX ODT can solve difficulty of swallowing of conventional tablets for some group of patients.