DESIGN AND OPTIMIZATION OF CAPTOPRIL SUBLINGUAL TABLETS: ENHANCEMENT OF PHARMACOKINETIC PARAMETERS IN HUMAN | ||||
| Al-Azhar Journal of Pharmaceutical Sciences | ||||
| Article 4, Volume 53, Issue 1 - Serial Number 53, March 2016, Page 90-107 PDF (877.76 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/ajps.2016.6889 | ||||
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| Authors | ||||
| Hossameldin Kadry1; Abdelsattar Omar* 2; Farag . Sherbiny3; Alaa Zaky4 | ||||
| 1Department of pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University | ||||
| 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Alsulaymanyah, Jeddah 21589, Saudi Arabia. | ||||
| 3Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt | ||||
| 4Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt. | ||||
| 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 32 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 X1 (crosscarmellose sodium, crosspovidone and sodium starch glycolate at 1:1:1 ratio) and using microcrystalline cellulose containing silicon dioxide (Prosolv-SMCC®) as a diluent (X2). Disintegration time and t90 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 T90 of captopril sublingual tablets. The lowest disintegration time (13.04 sec) and t90 (2.78 min) were showed by sublingual formulations composed of 7.82 % of superdisintegrants combination (X1) with 30.50 % of prosolv-SMCC (X2). 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 F-pharmaburst (12.2 and 16.3 sec respectively), and t90 (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. | ||||
| Keywords | ||||
| bioavailability; oral absorption; sublingual tablets; Response surface design; captopril; crosscarmellose sodium; crosspovidone; sodium starch glycolate; Superdisintegrant | ||||
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