Formulation and in vitro Evaluation of Ondansetron Hydrochloride Matrix Transdermal Systems Using Ethyl Cellulose/Polyvinyl Pyrrolidone Polymer Blends
Authors: Rajan Rajabalaya, Li-Qun Tor, Sheba David
Abstract:
Transdermal delivery of ondansetron hydrochloride (OdHCl) can prevent the problems encountered with oral ondansetron. In previously conducted studies, effect of amount of polyvinyl pyrrolidone, permeation enhancer and casting solvent on the physicochemical properties on OdHCl were investigated. It is feasible to develop ondansetron transdermal patch by using ethyl cellulose and polyvinyl pyrrolidone with dibutyl pthalate as plasticizer, however, the desired flux is not achieved. The primary aim of this study is to use dimethyl succinate (DMS) and propylene glycol that are not incorporated in previous studies to determine their effect on the physicochemical properties of an OdHCl transdermal patch using ethyl cellulose and polyvinyl pyrrolidone. This study also investigates the effect of permeation enhancer (eugenol and phosphatidylcholine) on the release of OdHCl. The results showed that propylene glycol is a more suitable plasticizer compared to DMS in the fabrication of OdHCl transdermal patch using ethyl cellulose and polyvinyl pyrrolidone as polymers. Propylene glycol containing patch has optimum drug content, thickness, moisture content and water absorption, tensile strength, and a better release profile than DMS. Eugenol and phosphatidylcholine can increase release of OdHCl from the patches. From the physicochemical result and permeation profile, a combination of 350mg of ethyl cellulose, 150mg polyvinyl pyrrolidone, 3% of total polymer weight of eugenol, and 40% of total polymer weight of propylene glycol is the most suitable formulation to develop an OdHCl patch. OdHCl release did not increase with increasing the percentage of plasticiser. DMS 4, PG 4, DMS 9, PG 9, DMS 14, and PG 14 gave better release profiles where using 300mg: 0mg, 300mg: 100mg, and 350mg: 150mg of EC: PVP. Thus, 40% of PG or DMS appeared to be the optimum amount of plasticiser when the above combination where EC: PVP was used. It was concluded from the study that a patch formulation containing 350mg EC, 150mg PVP, 40% PG and 3% eugenol is the best transdermal matrix patch compositions for the uniform and continuous release/permeation of OdHCl over an extended period. This patch design can be used for further pharmacokinetic and pharmacodynamic studies in suitable animal models.
Keywords: Ondansetron hydrochloride, dimethyl succinate, eugenol.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1078378
Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 2459References:
[1] Frame DG: Best practice management of CINV in oncology patients: I. Physiology and treatment of CINV. J Support Oncol, 8(1):pp 5-9, 2010.
[2] Swain K, Pattnaik S, Sahu SC, Patnaik KK, Mallick S: Drug in adhesive type transdermal matrix systems of ondansetron hydrocloride: optimization of permeation pattern using response surface methodology. J Drug Target, 18(2):106-114, 2009.
[3] Chandrashekar NS, Rani RHS: Physicochemical and pharmacokinetic parameters in drug selection and loading for transdermal drug delivery. Indian J Pharm Sci, 70(1):94-96, 2008.
[4] Swain K, Pattnaik S, Sahu SC, Mallick S: Feasibility assessment of ondansetron hydrochloride transdermal systems: Physicochemical characterization and In vitro permeation studies. Dev Ind Pharm, 28(5):706-714, 2009.
[5] Rajabalaya R, Khanam J, Nanda A: Design of a matrix patch formulation for long-acting permeation of diclofenac potassium. Asian J of Pharm Sci, 3(1): pp 30-39, 2008.
[6] Gal A, Nussinovitch A: Plasticizers in the manufacture of novel skinbioadhesive patches. Int J Pharm 370 (1-2); pp 103-109, 2008.
[7] Pattnaik S, Swain K, Mallick S, Lin ZQ: Effect of casting solvent on crystallinity of ondansetron in transdermal films. Int J Pharm, pp 406:106-110, 2011.
[8] Shoaib MH, Tazeen J, Merchant HA, Yousuf RI: Evaluation of drug release kinetics from Ibuprofen matrix tablets using HPMC. J Pharm Sci, 19(2): pp 119-124, 2006.
[9] Rajabalaya R, Sheba R, Kajal G, Sanjoy K, Jasmina, Arunabha N: Design and in vitro evaluation of chlorpheniramine maleate from different eudragit based matrix patches: Effect of platicizer and chemical enhancers. Ars Pharm, 50 (4): pp 177-194, 2010.