Formulation and Pharmacokinetic Evaluation of Controlled-Release Oxybutynin Tablets in Dogs

J Bae,Jw Park

doi:10.4314/tjpr.v14i3.2

Abstract

Purpose: To develop and optimize controlled-release (CR) oxybutynin chloride matrix tablets. Methods : Oxybutynin CR tablets were prepared by embedding drug-containing granules into a hydrogel matrix of hydroxypropyl methylcellulose (HPMC). A coating layer was then applied with a mixture of HPMC, ethylcellulose, shellac, and HPMC phthalate. The effect of several formulation variables on in vitro drug release was studied; furthermore, the drug release kinetics of the optimized formulation was evaluated. The in vivo pharmacokinetics of the optimized formulation was compared with those of commercial immediate-release and CR tablets in dogs. Results : The core tablets exhibited extended release consisting of drug release from the embedded granules through the erodible hydrogel matrix. Release rate was controlled by the amounts of swellingcontrol agent and hydrogel used. The optimized formulation followed zero-order release up to 24 h after an initial lag time. Maximum plasma drug concentration for the optimized and commercial CR tablets was 5.90 ± 1.42 and 6.47 ± 3.73 ng/mL, respectively, while the area under the plasma concentration– time curve was 101.40 ± 51.41 and 112.68 ± 65.89 ng∙h/mL, respectively. Conclusion : The formulated oxybutynin CR tablets exhibit prolonged drug release, thus rendering it a potentially suitable once-daily oral formulation for improved patient compliance. Keywords: Oxybutynin, Matrix tablet, Hydrogel, Oral controlled-release, Zero-order release,Pharmacokinetics

Highlights

Forms of drug administration that are capable of controlling drug release have become an important factor in medical treatment with respect to improved treatment effects, reduced side effects, and enhanced convenience for patients [1].Oxybutynin chloride is an anticholinergic agent that is commonly prescribed to treat symptoms of urge incontinence, urgency, and frequency arising from over-activity of the detrusor muscle [2]
The objective of the present study was to design a controlled-release (CR) oxybutynin form comprising drug-containing granules, granules embedded with an erosive hydrogel matrix core, and a coating layer to provide constant drug release with minimum dependence on pH or GI mobility
Zero-order release was apparently achieved for tablets containing 1 % swelling-control agent, and the formulation OXY/CR1 showed almost zero-order release and > 90 % drug release at 24 h

Summary

Introduction

Forms of drug administration that are capable of controlling drug release have become an important factor in medical treatment with respect to improved treatment effects, reduced side effects, and enhanced convenience for patients [1].Oxybutynin chloride is an anticholinergic (antimuscarinic) agent that is commonly prescribed to treat symptoms of urge incontinence, urgency, and frequency arising from over-activity of the detrusor muscle (overactive bladder) [2]. Oxybutynin is usually given at 15 mg/day in divided doses, and dry mouth secondary to its anticholinergic nature is the most commonly cited reason that patients either discontinue oxybutynin treatment or titrate to a lower dose [3] To overcome these limitations, an extended-release oxybutynin tablet comprising a two-part core tablet surrounded by a semi-permeable membrane with a laser-drilled orifice on the drug-containing side of the tablet was developed. An extended-release oxybutynin tablet comprising a two-part core tablet surrounded by a semi-permeable membrane with a laser-drilled orifice on the drug-containing side of the tablet was developed Because this delivery system is primarily governed by osmosis, the drug is delivered into the gastrointestinal (GI) tract at a constant and controlled rate over a 24-h period, independent of pH and GI mobility [4]. This system can minimize the peak/trough fluctuations in the plasma drug level associated with repeated dosing, disadvantages include the complicated nature of the system, high cost, and restricted drug release sites

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