DEVELOPMENT AND IN VITRO–IN VIVO EVALUATION OF GASTRORETENTIVE FLOATING TABLETS OF AN ANTIRETROVIRAL AGENT RITONAVIR
Objective: The present research work concerns the development of the extended release of Ritonavir floating matrix tablets, designed to prolong the gastric residence time, increase the drug bioavailability, and diminish the side effects of irritating drugs.
Methods: The floating tablets of Ritonavir were prepared by direct compression method using different grades of hydroxypropyl methylcellulose (HPMC), crospovidone, Polyox WSR 303, and sodium bicarbonate, as gas generating agent. Evaluation parameters and in vivo radiographic studies were conducted in suitable model.
Results: Among all formulations, F21 was chosen as optimized formulation based on evaluation parameters such as floating lag time (33 s), total floating time (>24 h), and in vitro dissolution studies. From in vitro dissolution studies, the optimized formulation F21 and marketed product were shown 98.67% and 91.46±5.02% of drug release, respectively. The main appliance of medication discharge follows zero-order kinetics and non- Fickian transport by coupled diffusion and erosion. In vivo experiments maintained the potentials in extending the gastric residence time in the fasted state in beagle dogs. The mean gastric residence time of the optimized formulation found to be 330 min±40 in the stomach, where longer gastric residence time is an important condition for prolonged or controlled drug release and also for enhanced bioavailability.
Conclusion: From in vitro and in vivo radiographic studies, Ritonavir floating tablets estimated to provide novel choice for harmless, inexpensive, and extended release for the effective management of AIDS.
2. Emara LH, Abdou AR, El-ashmawy AA, Mursi NM. Preparation and evaluation of metronidazole sustained release floating tablets. Int J Pharm Pharm Sci 2014;6:198-204.
3. Mojaverian P, Vlasses PH, Kellner PE, Rocci ML Jr. Effects of gender, posture, and age on gastric residence time of an indigestible solid: Pharmaceutical considerations. Pharm Res 1988;5:639-44.
4. Deshpande AA, Rhodes CT, Shah NH. Controlled release drug delivery system for prolonged gastric residence. Drug Dev Ind Pharm 1996;22:531-9.
5. Sawant K, Patel M, Patel J, Mundada P. Formulation, optimization, characterization and in vivo anti-ulcer activity of esomeprazole magnesium trihydrate gastro-resistant microspheres. Int J Pharm Pharm Sci 2014;6:198-204.
6. Hwang SK, Park H, Park K. Gastric retentive drug delivery systems. Crit Rev Ther Drug Carrier Syst 1998;15:243-84.
7. Gruber P, Rubinstein A, Li VH, Bass P, Robinson JR. Gastric emptying of nondigestible solids in the fasted dog. J Pharm Sci 1987;76:117-22.
8. Desai S, Bolton S. A floating controlled-release drug delivery system: In vitro-in vivo evaluation. Pharm Res 1993;10:1321-5.
9. Li S, Lin S, Chien YW, Daggy BP, Mirchandani HL. Statistical optimization of gastric floating system for oral controlled delivery of calcium. AAPS PharmSciTech 2001;2:E1.
10. Li S, Lin S, Daggy BP, Mirchandani HL, Chien YW. Effect of formulation variables on the floating properties of gastric floating drug delivery system. Drug Dev Ind Pharm 2002;28:783-93.
11. Sweetman SC. Martindale: The Complete Drug Reference. 35th ed. London: Pharmaceutical Press; 2007. p. 766-79.
12. Rao TR, Krishna KB, Hussain MA, Anjum M, Azizurrahman M. Formulation and evaluation of gastroretentive floating tablets of quetiapine fumarate. Res J Pharm Biol Chem Sci 2014;5:975-8585.
13. Nasrin N, Asaduzzaman M, Rumana M, Rizwan F, Alam A. A comparative study of physical parameters of selected ketorolac tromethamine tablets available in the pharma market of Bangladesh. J Appl Pharm Sci 2008;1:101-3.
14. Penners G, Lustig K, Jorg PVG. Expandable pharmaceutical forms. US Patent No. 5; 1997. p. 651-985.
15. Phuapradit W, Bolton S. Influence of tablet density on oral absorption of sustained release acetaminophen matrix tablets. Drug Dev Ind Pharm 1991;17:1097-107.
16. Phuapradit W. Influence of Tablet Buoyancy on Oral Absorption of Sustained Release Acetaminophen Matrix Tablets. Jamaica: St John’s University; 1989.
17. Ma?gorzata W, Marcin Z, Aleksandra A. Tasting cetirizine-based microspheres with an electronic tongue. Sens Actuators B Chem 2016;238:1190-8.
18. Janssen M, Timur UT, Woike N, Welting TJ, Draaisma G, Gijbels M, et al. Celecoxib-loaded PEA microspheres as an auto regulatory drug-delivery system after intra-articular injection. J Control Release 2016;244:30-40.
19. Kumar TL, Lal KM. Stability study and in-vivo evaluation of lornoxicam loaded ethyl cellulose microspheres. Int J Pharm Sci Drug Res 2014;6:26-30.
20. Singh K, Kumar A, Langyan N, Ahuja M. Evaluation of Mimosa pudica seed mucilage as sustained-release excipient. AAPS PharmSciTech 2009;10:1121-7.
21. Baumgartner S, Kristl J, Vrecer F, Vodopivec P, Zorko B. Optimisation of floating matrix tablets and evaluation of their gastric residence time. Int J Pharm 2000;195:125-35.
22. Siepmann J, Kranz H, Bodmeier R, Peppas NA. HPMC-matrices for controlled drug delivery: A new model combining diffusion, swelling, and dissolution mechanisms and predicting the release kinetics. Pharm Res 1999;16:1748-56.
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