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

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 swelling-control 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.