Abstract
The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing metoprolol tartrate (MT) as a model drug by the optimization technique. A 23 factorial design was employed in formulating the GFDDS with total polymer content-to-drug ratio (X1), polymer-to-polymer ratio (X2), and different viscosity grades of hydroxypropyl methyl cellulose (HPMC) (X3) as independent variables. Four dependent variables were considered: percentage of MT release at 8 hours, T50%, diffusion coefficient, and floating time. The main effect and interaction terms were quantitatively evaluated using a mathematical model. The results indicate that X1 and X2 significantly affected the floating time and release properties, but the effect of different viscosity grades of HPMC (K4M and K10M) was nonsignificant. Regression analysis and numerical optimization were performed to identify the best formulation. Fickian release transport was confirmed as the release mechanism from the optimized formulation. The predicted values agreed well with the experimental values, and the results demonstrate the feasibility of the model in the development of GFDDS.
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References
Hoffman BB. Catecholamines, sympathomimetics drugs, and adrenergic receptor antagonists. In: Hardman JG, Limbird LE, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill: 2001:255–256.
Kendall MJ, Maxwell SR, Sandberg A, Westergren G. Controlled release metoprolol. Clinical pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 1991;21:319–330.
Jobin G, Cortot A, Godbillon J, et al. Investigation of drug absorption from the gastrointestinal tract of man, I: metoprolol in stomach, duodenum, and jejunum. Br J Clin Pharmacol. 1985;19:97S-105S.
Moes AJ. Gastroretentive dosage forms. Crit Rev Ther Drug Carrier Syst. 1993;10:143–159.
Baumgartner S, Kristl J, Vrecer F, Vodopivec P, Zorko B. Optimization of floating matrix tablets and evaluation of their gastric residence time. Int J Pharm. 2000;195:125–135.
Deshpande AA, Shah NH, Rhodes CT, Malick W. Development of a novel controlled-release system for gastric retention. Pharm Res. 1997;14:815–819.
Singh BN, Kim KH. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. J Control Release. 2000;63:235–259.
Li S, Lin S, Daggy BP, Mirchandani HL, Chien YW. Effect of HPMC and Carbopol on the release and floating properties of Gastric Floating Drug Delivery System using factorial design. Int J Pharm. 2003;253:13–22.
Nur AO, Zhang JS. Captopril floating and/or bioadhesive tablets: design and release kinetics. Drug Dev Ind Pharm. 2000;26:965–969.
Hilton AK, Deasy PB. In vitro and in vivo evaluation of an oral sustained-release floating dosage form of amoxycillin trihydrate. Int J Pharm. 1992;86:79–88.
Jimenez-Castellanos MR, Zia H, Rhodes CT. Design and testing in vitro of a bioadhesive and floating drug delivery system for oral application. Int J Pharm. 1994;105:65–70.
Wei Z, Yu Z, Bi D. Design and evaluation of a two-layer floating tablet for gastric retention using cisapride as model drug. Drug Dev Ind Pharm. 2001;27:469–474.
Korsmeyer RW, Doelker GEP, Peppas NA. Mechanisms of potassium chloride from compressed, hydrophilic, polymeric matrices: effect of entrapped air. J Pharm Sci. 1983;72:1189–1191.
Hwang SJ, Park H, Park K. Gastric retentive drug-delivery systems. Crit Rev Ther Drug Carrier Syst. 1998;15:243–284.
Fessi H, Marty JP, Puisieux F, Carstensen JT. Higuchi square root equation applied to matrices with high content of soluble drug substance. Int J Pharm. 1978;1:265–274.
Fonner DE Jr, Buck JR, Banker GS. Mathematical optimization techniques in drug product design and process analysis. J Pharm Sci. 1970;59:1587–1596.
Xu G, Sunada H. Influence of formulation change on drug release kinetics from hydroxypropylmethylcellulose matrix tablets. Chem Pharm Bull (Tokyo). 1995;43:483–487.
Ingani HM, Timmermans J, Moes AJ. Conception and in vivo investigation of peroral sustained release floating dosage forms with enhanced gastrointestinal transit. Int J Pharm. 1987;35:157–164.
Menon A, Ritschel WA, Sakr A. Development and evaluation of a monolithic floating dosage form for furosemide. J Pharm Sci. 1994;83:239–245.
Smart JD, Kellaway IW, Worthing HEC. An in vitro investigation of mucoadhesive materials for use in controlled drug delivery. J Pharm Pharmacol. 1984;36:295–299.
Chueh HR, Zia H, Rhodes CT. Optimization of sotalol floating and bioadhesive extended release tablet formulations. Drug Dev Ind Pharm. 1995;21:1725–1747.
Velasco MV, Ford JL, Rowe P, Rajabi-Siahboomi AR. Influence of drug: hydroxypropylmethylcellulose ratio, drug and polymer particle size and compression force on the release of diclofenac sodium from HPMC tablets. J Control Release. 1999;57:75–85.
Sheth PR, Tossounian JL, inventors. Sustained release tablet formulation. US patent 4 140 755. February 20, 1979.
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Published: April 7, 2006
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Narendra, C., Srinath, M.S. & Babu, G. Optimization of bilayer floating tablet containing metoprolol tartrate as a model drug for gastric retention. AAPS PharmSciTech 7, 34 (2006). https://doi.org/10.1208/pt070234
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DOI: https://doi.org/10.1208/pt070234