APPLICATION OF CENTRAL COMPOSITE DESIGN FOR OPTIMIZATION OF EFFERVESCENT FLOATING TABLETS USING HYDROPHILIC POLYMERS
The aim of the present study was to optimize effervescent floating tablets of Cefixime Trihydrate as model drug by optimization of polymers concentration using central composite design. Mean dissolution time (MDT), time required to release 50% of drug (t50%), drug release at 2Â h (R2h) and dissolution efficiency in 2 h (DE2h) were taken as target responses, where as the quantity of different polymers such as Carbopol 934P (viscoelastic agent), Sod.CMC (swelling agent) were considered as independent variables. A second-order polynomial equation was determined by the multiple regression analysis of the experimental data. The best fitting model was selected based on the comparisons of the coefficient of determination (r2), adjusted coefficient of determination (adj. r2). In addition, analysis of variance (ANOVA) was used to evaluate the statistical significance of the quadratic polynomial model. The optimum values for the critical components were obtained as 13.151% Carbopol 934P and 4.08% of Sod.CMC with predicted value of 4.926 h MDT, 5.257 h t50%, 27.6316% R2h and 16.5951% DE2h from desirability and overlay plot. Further the reliability of the model was checked by validating the observed responses from optimized formula. The drug release from characteristics of all formulations followed Higuchi model with a non-Fickian diffusion mechanism. Further the data of FTIR study showed there was no interaction of drug and excipients used for the preparation of floating tablets.
Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â ÂKey words: Central composite design, Cefixime Trihydrate, Mean dissolution time, Fickian diffusion, dissolution efficiency
2. Arora S, Ali J, Ahuja A, Khar RK, Baboota S. Floating drug delivery systems: A review. AAPS Pharm SciTech 2005 19;6(3):E372-90.
3. Ponchel G, Irache J. Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Adv Drug Deliv Rev 1998;34(2-3):191-219.
4. Davis SS, Stockwell AF, Taylor MJ, Hardy JG, Whalley DR, Wilson CG, et al. The effect of density on the gastric emptying of single- and multiple-unit dosage forms. Pharm Res 1986;3(4):208-13.
5. MoÃ«s AJ. Gastroretentive dosage forms. Crit Rev Ther Drug Carrier Syst 1993;10(2):143-95.
6. Fell JT, Whitehead L, Collet JH. Prolonged gastric retention using floating dosage forms. Pharm Technol 2000;24(3):82-90.
7. Anthony CM, Osselton MD, Widdep B. Clark Analysis of Drugs and Poisons. Vol. 2. No. 3. London, UK: Pharmaceutical Press of Great Britain; 2004. p. 763-4.
8. Indian Pharmacopoeia. New Delhi: Ministry of Health and Family Welfare, Government of India, Controller of Publications; 1996. p. 736.
9. Ozdemir N, Ordu S, Ozkan Y. Studies of floating dosage forms of furosemide: In vitro and in vivo evaluations of bilayer tablet formulations. Drug Dev Ind Pharm 2000;26(8):857-66.
10. Shah KU, Khan GM. Regulating drug release behavior and kinetics from matrix tablets based on fine particle-sized ethyl cellulose ether derivatives: An in vitro and in vivo evaluation. ScientificWorldJournal 2012;2012:842348.
11. Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13(2):123-33.
12. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol 1975;27(1):48-9.
13. Srikanthn MV, Rao NS, Sunil SA, Ram BJ, Kolapalli VR. Statistical design and evaluation of a propranolol HCl gastric floating tablet. Acta Pharm Sin B 2012;2(1):260-9.
14. Durrani MJ, Todd R, Andrew A. Proceedings of Controlled Release Bioactive Materials. 19th International Symposium; 1992. p. 19.411.
15. Châ€™ng HS, Park H, Kelly P, Robinson JR. Bioadhesive polymers as platforms for oral controlled drug delivery II: Synthesis and evaluation of some swelling, water-insoluble bioadhesive polymers. J Pharm Sci 1985;74:399-405
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.