Chronomodulated press-coated pulsatile therapeutic system for aceclofenac: optimization of factors influencing drug release and lag time

Abstract

Background:The objective of this study was to develop and evaluate a press-coated pulsatile drug delivery system intended for treatment of early morning stiffness and symptomatic relief from pain in patients with rheumatoid arthritis. Methods: The formulation involved press coating of a rupturable coat around a rapidly d isintegrating core tablet of aceclofenac. A three-factor, two-level, full factorial design was used to i nvestigate the influence of amount of glyceryl behenate, amount of sodium chloride in the coating c omposition, and the coating level on the responses, ie, lag time to release and amount of aceclofenac released in 450 minutes. Results: Glyceryl behenate and the coating level had a significant influence on lag time, while sodium chloride helped in the rupture of the coat by acting as a channeling agent. After the coat was ruptured, the core tablet showed a rapid release of aceclofenac due to the presence of Ac-Di-Sol ® . Graphical analysis of effects by Lenth's method and Bayesian analysis of coefficients enabled identification of variables active on the selected responses. The optimized formulation comprised 20% w/w glyceryl behenate and 2.2% w/w sodium chloride with a 650 mg coating level, and showed a desired lag time of 358.23 minutes, which mimics the fluctuating symptoms of rheumatoid arthritis, followed by rapid release of aceclofenac.