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

PLoS One. 2021 Mar 16;16(3):e0246648. doi: 10.1371/journal.pone.0246648. eCollection 2021.


INTRODUCTION: Orally disintegrating tablet (ODT) is a dosage form that overcomes the problem of swallowing which is prevalent in about 35% of the general population. Co-trimoxazole (CTX) is given for patients with HIV for the prophylaxis of opportunistic infection (OI), commonly for pneumocystis carinii pneumonia. It was reported that CTX was associated with a 25-46% reduction in mortality among individuals infected with HIV in sub-Saharan Africa. Esophageal candidiasis which usually comes along with HIV/AIDS is one of AIDS defining illness affecting up to 1 in 5 of people with AIDS. This opportunistic illness is manifested by painful or difficulty of swallowing. In this respect, CTX ODT offer the advantages of both liquid dosage forms in terms of easy swallowing thereby improve patient compliance and solid dosage forms in terms of dose uniformity, stability, lower production, and transportation costs. The objective of this study was to formulate, characterize and optimize CTX ODT which could overcome swallowing problem and improve patient compliance. Co-trimoxazole ODTs were prepared by direct compression technique using a semi synthetic super disintegrant (crospovidone) along with other excipients. Two taste masking techniques were employed, addition of sweetening agent, and solid dispersion by using a pH sensitive polymer, 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 crospovidone, compression force (CF) and Hydroxypropyl cellulose (HPC) on disintegration time, friability and wetting time (WT). Factorial design was used as it enables simultaneous evaluation of formulation variables and their interaction effect. From the preliminary study, the factors that were found significant were further optimized using central composite design. Design-Expert software was employed to carry out the experimental design. 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 superdisintegrant 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. Central composite design was effectively used to model and optimize friability, DT and WT. The method was found effective for estimating the effect of independent variables on the dependent variables by using polynomial equation and surface plots. Optimization of the response variables was possible by using both numerical and graphical optimization and the predicted optimal conditions were confirmed experimentally and were found to be in good agreement within 5% of the predicted responses. The results of the study showed that CTX ODT had significantly rapid disintegration, less than 1% friability and enhanced dissolution profiles. The successful formulation of CTX ODT can solve difficulty of swallowing of conventional tablets for some group of patients which are unable to swallow solid oral dosage form.

PMID:33725014 | DOI:10.1371/journal.pone.0246648