In Vitro Release Kinetics and Bioavailability of Gastroretentive Cinnarizine Hydrochloride Tablet
First Online: 25 February 2010 Received: 22 July 2009 Accepted: 12 January 2010 DOI:
Cite this article as: Nagarwal, R.C., Ridhurkar, D.N. & Pandit, J.K. AAPS PharmSciTech (2010) 11: 294. doi:10.1208/s12249-010-9380-5 Abstract
An oral sustained release dosage form of cinnarizine HCl (CNZ) based on gastric floating matrix tablets was studied. The release of CNZ from different floating matrix formulations containing four viscosity grades of hydroxypropyl methylcellulose, sodium alginate or polyethylene oxide, and gas-forming agent (sodium bicarbonate or calcium carbonate) was studied in simulated gastric fluid (pH 1.2). CNZ release data from the matrix tablets were analyzed kinetically using Higuchi, Peppas, Weibull, and Vergnaud models. From water uptake, matrix erosion studies, and drug release data, the overall release mechanism can be explained as a result of rapid hydration of polymer on the surface of the floating tablet and formation of a gel layer surrounding the matrix that controls water penetration into its center. On the basis of
in vitro release data, batch HP1 (CNZ, HPMC-K100LV, SBC, LTS, and MgS) was subjected to bioavailability studies in rabbits and was compared with CNZ suspension. It was concluded that the greater bioavailability of HP1 was due to its longer retention in the gastric environment of the test animal. Batch no. HP1 of floating tablet in rabbits demonstrated that the floating tablet CNZ could be a 24-h sustained release formulation. Key words bioavailability cinnarizine HCl floating tablet HPMC kinetic models References
Ahmed IS, Ayres JW. Bioavailability of riboflavin from a gastric retention formulation. Int J Pharm. 2007;330:146–54.
Williams MF, Dukes GE, Heizer W, Han Y, Herman DJ, Lampin T,
. Influence of gastrointestinal site of drug delivery on the absorption characteristics of ranitidine. Pharm Res. 1992;9:1190–4.
Hwang SJ, Park H, Park K. Gastric retentive drug-delivery systems. Crit Rev Ther Drug Carrier Syst. 1998;15:243–84.
Desai S, Bolton S. A floating controlled-release drug delivery systems:
in vitro–in vivo
evaluation. Pharm Res. 1993;10:1321–5.
Hilton AK, Deasy PB.
evaluation of an oral sustained-release floating dosage form of amoxycillin trihydrate. Int J Pharm. 1992;86:79–88.
Matharu RS, Singhavi NM. Novel drug delivery system for captopril. Drug Dev Ind Pharm. 1992;18:1567–74.
Sheth PR, Tossounian J. The hydrodynamically balanced system (HBSE): a novel drug delivery system for oral use. Drug Dev Ind Pharm. 1984;10:313–39.
Chen GL, Hao WH.
performance of floating sustained-release capsule of verapamil. Drug Dev Ind Pharm. 1998;24:1067–72.
Fukuda M, Peppas NA, McGinity JW. Floating hot-melt extruded tablets for gastroretentive controlled drug release system. J Control Release. 2006;115:121–9.
Wei Z, Yu Z, Bi D. Design and evaluation of a two-layer floating tablet for gastric retention using cisapride as a model drug. Drug Dev Ind Pharm. 2001;27:469–74.
Xiaoqiang X, Minjie S, Feng Z, Yiqiao H. Floating matrix dosage form for phenoporlamine hydrochloride based on gas forming agent:
evaluation in healthy volunteers. Int J Pharm. 2006;310:139–45.
Ichigawa M, Watanabe S, Miyake Y. A new multiple-unit oral floating dosage system. I: preparation and
evaluation of floating and sustained-release characteristics. J Pharm Sci. 1991;80:1062–106.
Baumgartner S, Tivadar A, Vrečer F, Kristl J. Development of floating tablets as a new approach to the treatment of Helicobacter pylori infections. Acta Pharm. 2001;51:21–33.
Cedillo-Ramirez E, Villafuerte-Robles L, Hernandez-Leon A. Effect of added pharmatose DCL11 on the sustained-release of metronidazole from methocel K4M and carbopol 971 NF floating matrices. Drug Dev Ind Pharm. 2006;32:955–65.
Sopimath SK, Kulkarni AR, Rudzinski WE, Aminabhavi TM. Microspheres as floating drug delivery systems to increase gastric retention of drugs. Drug Metab Rev. 2001;33:149–60.
Hasan SM, Elmosallamy AF, Abbas AB. LC and TLC determination of cinnarizine in pharmaceutical preparations and serum. J Pharm Biomed Anal. 2002;28:711–9.
Roy DS, Rohera BD. Comparative evaluation of rate of hydration and matrix erosion of HEC and HPC and study of drug release from their matrices. Eur J Pharm Sci. 2000;16:193–9.
Ebube NK, Hikal AH, Jones AB. Sustained release of acetaminophen from heterogeneous matrix tablets: influence of polymer ratio, polymer loading, and co-active on drug release. Pharm Dev Technol. 1997;2:161–70.
Choi BY, Park HJ, Hwang SJ, Park JB. Preparation of alginate beads for floating drug delivery system: effects of CO2 gas-forming agents. Int J Pharm. 2002;239:81–91.
Parikh RK, Parikh CP, Delvadia RR, Patel SM. A novel multicompartment dissolution apparatus for evaluation of floating dosage form containing poorly soluble weakly basic drug. Dissolution Technologies. 2006;13:14–9.
Wan LS, Heng PW, Wong LF. Relationship between swelling and drug release in a hydrophilic matrix drug. Dev Ind Pharm. 1993;19:1201.
Colombo P, Bettini R, Santi P, Ascentiis A, Peppas NA. Analysis of the swelling and release mechanisms from drug delivery systems with emphasis on drug solubility and water transport. J Control Release. 1996;39:231.
Mitchell K, Ford JL, Armstrong DJ, Elliot PN, Hogan JE, Rostron C. The influence of drugs on the properties of gels and swelling characteristics of matrices containing methylcellulose or hydroxypropylmethylcellulose. Int J Pharm. 1993;100:165–73.
Yan G, Li H, Zhang R, Ding D. Preparation and evaluation of a sustained-release formulation of nifedipine HPMC tablets. Drug Dev Ind Pharm. 2000;26:681–6.
Conti S, Maggi L, Segale L, Ochoa Machiste E, Conte U, Grenier P,
. Matrices containing NaCMC and HPMC: 1. Dissolution performance characterization. Int J Pharm. 2007;333:136–42.
Harland R, Gazzaninga A, Sangalli M, Colomb P, Peppas NA. Drug/polymer matrix swelling and dissolution. Pharm Res. 1988;5:488.
Bain J, Tan S, Gandarton D, Solomon M. Comparison of the
release characteristics of a wax matrix and a hydrogel sustained release diclofenac sodium tablet. Drug Dev Ind Pharm. 1991;17:215.
Alderman DA. A review of cellulose ethers in hydrophilic matrices for oral controlled-release dosage forms. Int J Pharm. 1984;5:1–9.
Hodson AC, Mitchell JR, Davies MC, Melia CD. Structure and behavior in hydrophilic matrix sustained release dosage forms: 3. The influence of pH on the sustained-release performance and internal gel structure of sodium alginate matrices. J Control Release. 1995;33:143–52.
Costa C, Lobo CJM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13:123–33.
Hasan EI, Amro BI, Arafat T, Badwan AA. Assessment of a controlled release hydrophilic matrix formulation for metoclopramide HCl. Eur J Pharm Biopharm. 2003;55:339–44.
Paulson SK, Vaughn MB, Jessen SM, Lawal Y, Gresk CJ, Yan B,
. Pharmacokinetics of celecoxib after oral administration in dogs and humans: effect of food and site of absorption. J Pharmacol Exp Ther. 2001;297(2):638–45.
PubMed Copyright information
© American Association of Pharmaceutical Scientists 2010