Design and Optimization of Captopril Sublingual Tablets: Enhancement of Pharmacokinetic Parameters in Human

Abstract

Oral mucous membrane of drug delivery is considered to be a promising alternative to the oral route. Sublingual route is a useful when rapid onset of action is desired than orally administered tablets. The objective of this study was to develop the sublingual tablet of captopril and improve its bioavailability. Captopril is the drug of choice in treatment of hypertension crisis or acute heart failure. Improvement of drug absorption and bioavailability was achieved by decreasing the pH of the mouth using citric acid. A 3 2 full factorial design was applied to optimize the formulations. Nine batches were prepared and evaluated to developing and optimizing sublingual tablets of water soluble drug (captopril). The optimization design was used to obtained the concentration of mixture superdisintegrants X 1 (crosscarmellose sodium, crosspovidone and sodium starch glycolate at 1:1:1 ratio) and using microcrystalline cellulose containing silicon dioxide (Prosolv-SMCC®) as a diluent (X 2 ). Disintegration time and t 90 values used as dependent variables for optimization to obtain the desirable optimized formula. According to the results, the selected variables have a strong influence on disintegration time and T 90 of captopril sublingual tablets. The lowest disintegration time (13.04 sec) and t 90 (2.78 min) were showed by sublingual formulations composed of 7.82 % of superdisintegrants combination (X 1 ) with 30.50 % of prosolv-SMCC (X 2 ). So, this formula was chosen as the optimized formula. The F-optimized formula was compared with the marketed tablet pharmaburst® formula. It is clear from the result that the F-optimize formula had a very significant lower disintegration time than Fpharmaburst (12.2 and 16.3 sec respectively), and t 90 (3.2 and 5.0 minute respectively). The pharmacokinetic parameter for the F-optimized showed a significant (P ≤ 0.05) increase in maximum plasma concentration from 180.0 to 286.5ng/mL, and a shortening of the time taken to reach maximum plasma concentration to 45 min in comparison with the marketed tablet. Finally, the F-optimize improved oral absorption of captopril sublingual and a subsequent acceleration of clinical effect, which is favored for hypertensive crises and cardiac disorders.

Formulation and Characterization of Odt Using Different Co-Process Containing Daclatsvir: In Vitro and in Vivo Pharmacokinetics Study on Healthy Volunteers for Hepatitis C Treatment

“…In vitro dissolution tests were performed with a dissolution tester, set with a paddle speed of 50 rpm, using 300 ml of distilled water at 37±0.5 °C as a dissolution medium. At specified time intervals (5,10,15,20,30,45,60 min) aliquots of 3 ml of dissolution media were withdrawn and replaced with an equal volume of the fresh medium drug content was assayed spectrophotometrically at 214 nm. Drug concentration was expressed as the cumulative percent drug dissolved.…”