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 disintegrating core tablet of aceclofenac. A three-factor, two-level, full factorial design was used to investigate the influence of amount of glyceryl behenate, amount of sodium chloride in the coating composition, 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.

Keywords::

• chronotherapy
• pulsatile delivery
• rupturable coat
• aceclofenac