CONTROLLED RELEASE FLOATING ORAL IN SITU GEL OF ITOPRIDE HYDROCHLORIDE USING PH SENSITIVE POLYMER
Keywords:
Gastro retentive drug delivery, Oral in situ gel, Sodium alginate, Calcium carbonateAbstract
Objective: In situ gels are suitable to overcome problems of immediate release and short gastrointestinal residence of liquids. These systems are liquids before administration and on contact with gastric contents are converted to gel. The present work deals with the formulation, evaluation and optimization of pH triggered floating oral in situ gel of Itopride hydrochloride by using sodium alginate as a gelling polymer and HPMC K100M as a release retardant polymer.
Methods: A 32 factorial designs was carried out and the effect of variation in concentrations of sodium alginate and calcium carbonate on percent drug release at 1 h, 6 h, gel strength and T50% i. e. time required for the release 50 % of loaded drug was evaluated. The gels were studied for their viscosity, in vitro buoyancy and drug release, in vitro gelling capacity, density, gel strength.
Results: The results of a 32 full factorial design revealed that the concentration of sodium alginate and concentration of calcium carbonate significantly affected the dependent variables. A controlled release profile was observed for these formulations. The dissolution data were fitted to various kinetic models which indicated diffusion controlled release profile. In vivo studies revealed higher Tmax of gel compared to plain drug which is suggestive of slower absorption. However, the AUC0-12 h was found to be nearly 90% higher than plain drug. Thus, bioavailability was found to be increased with in situ gel of Itopride hydrochloride.
Conclusion: Floating oral in situ gelling system of amoxicillin can be formulated using sodium alginate as a gelling polymer to sustain the drug release for 12 h with diffusion controlled release kinetics.
Downloads
References
Miyazaki S, Endo K, Kawasaki N, Kubo W, Watanabe H, Attwood D. Oral sustained delivery of paracetamol from in situ gelling xyloglucan formulations. Drug Del Ind Pharm 2003;29(2):113-9.
Rozier C, Mazuel J, Grove B, Plazonnet. Gelrite: a novel ion activated in situ gelling polymer for ophthalmic vehicles. Effect on bioavailability of timolol. Int J Pharm 1989;57:163–8.
Jadhav S Land, Banerjee SK. Formulation and evaluation of floating in situ gel of Nizatidine. Int J Res Pharm Sci 2013;4(2):250-5.
Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Del Rev 2001;53:321-39.
Concheiro Angel. Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery. Adv Drug Del Rev 2013;65:1148-71.
S Gupta, V Kapoor, B Kapoor. JK Science. J Med Edu Res 2004;6:106-08.
P Chippa, AM Pethe, S Upadhyay, A Tekade. J Pharm Res 2009;2(8)1404-08.
Miteshkumar J Patel. Strategy for development of pH triggered floating in-situ gel of Levetiracetam. Am J Pharm Tech Res 2012;2(3):828-41.
Wamorkar V, Varma MM, Manjunath SY. Formulation and optimization of in situ gel of metoclopramide using 32full factorial design. J Pharm Res 2011;4(8):2780-83.
Patel DM, Patel DK, Patel CN. Formulation and evaluation of floating oral in situ gelling system of amoxicillin. Int Scholarly Res Network 2011;8:1-8.
Jayswal BD, Yadav VT, Patel KN, Patel BA, Patel PA. Formulation and evaluation of floating in situ gel based gastro retentive drug delivery of Cimetidine. Int J For Pharm Res Schol 2012;9(1):327-37.
Mushiroda T, Douya R, Takahara E. The involvement of flavin-containing monooxygenase but not CYP3A4 in metabolism of itopride hydrochloride, a gastroprokinetic agent: comparison with cisapride and mosapride citrate. Drug Metab Dispos 2000;28(10):1231-37.
Attwood D, Kubo W, Miyazaki S. Int J Pharm 2003;25:855–64.
Attwood D, Kubo W, Miyazaki S, Itoh K, Fujiwara M, Tomohiro H, et al. Int J Pharm 2006;312:37–42.
Martin Alfred, James Swarbrick. Physical Chemical Principles in the Pharmaceutical Sciences, Physical Pharmacy, 3rd edition. Varghese Publishing House, Indian Edition; 1993. p. 513-6.
Dettmar PW, Hampson FC, Farndale A, Strugala V, Sykes J, Jolliffe I. Alginate rafts and their characterization. Int J Pharm 2005;294:137–147.
Rjalakshmi R, Sireesha A, Subash KV, Venkata PP, Mahesh K and Naidu KL, (2011), Development and evaluation of a novel floating in situ gelling system of levofloxacin hemihydrates. Int. J. Innov. Pharm. Res., 2(1), 102-108.
Miteshkumar J. Patel, Strategy for development of pH triggered floating in-situ gel of Levetiracetam, Am. J. PharmTech Res. 2012;2(3), 828-841.
Preetha PJ, Karthika K, Rekha NR, Elshafie K, Formulation and evaluation of in Situ ophthalmic gel of Diclofenac Sodium, J. of Chemical and Pharm. Res., 2010, 2(3), 528-535.
Miyazaki S, Endo K Kawasaki N, Kubo W, Watanabe H, Attwood D. Oral sustained delivery of paracetamol from in situ gelling xyloglucan formulations. drug dev Ind Pharm., 29, 2003. 113-119.
Higuchi T., J. pharm. Sci., (1963). 52, 1145-1149.
Korsmeyer R. W., Gurny R., Peppas N. A, Int. J. Pharm., (1983) 15, 25-35.
Vineeta Khanwilkar, Stability indicating high performance thin-layer chromatographic method for simultaneous estimation of Pantaprazole Sodium and itopride hydrochloride in combined dosage form, J. of Pharm. Analysis 2011;1(4):275-283.
A Suganthi, Simultaneous HPTLC Determination of Rabeprazole and itopride hydrochloride from their combined dosage form, Ind. J. of pharm. Sci., May-June 2008, 70(3):366-368.
Y Mahagen; V Patidhar; Y Balaram; P Gopkumar; G Sridevi, Res. and rev: J of pharm and pharm. Sci.,2014,3(1), 37-43.
B. Mishra Floating in situ gelling system for stomach site-specific delivery of Clarithromycin to eradicate H. pylori. J of cont rel., 2008., 34-41.
www. mri. medagencies. org/download (accessed on 13/08/2014).
Mushiroda T, Douya R, Takahara E, Nagata O. The involvement of flavin containing monooxygenase but not CYP3A4 in metabolism of itopride hydrochloride, a gastrokinetic agent: comparison with cisapride and mosapride citrate. Drug Metab Dispos 2000;28:1231-37.