Multiple response optimization of processing and formulation parameters of Eudragit RL/RS-based matrix tablets for sustained delivery of diclofenac

Abstract

Context: Multiple response optimization is an efficient technique to develop sustained release formulation while decreasing the number of experiments based on trial and error approach.

Objective: Diclofenac matrix tablets were optimized to achieve a release profile conforming to USP monograph, matching Voltaren^®SR and withstand formulation variables. The percent of drug released at predetermined multiple time points were the response variables in the design. Statistical models were obtained with relative contour diagrams being overlaid to predict process and formulation parameters expected to produce the target release profile.

Materials and methods: Tablets were prepared by wet granulation using mixture of equivalent quantities of Eudragit RL/RS at overall polymer concentration of 10–30%w/w and compressed at 5–15KN.

Results and discussion: Drug release from the optimized formulation E4 (15%w/w, 15KN) was similar to Voltaren, conformed to USP monograph and found to be stable. Substituting lactose with mannitol, reversing the ratio between lactose and microcrystalline cellulose or increasing drug load showed no significant difference in drug release. Using dextromethorphan hydrobromide as a model soluble drug showed burst release due to higher solubility and formation of micro cavities.

Conclusion: A numerical optimization technique was employed to develop a stable consistent promising formulation for sustained delivery of diclofenac.

Keywords:

• Controlled release
• desirability approach
• wet granulation
• factorial design
• stability
• diclofenac

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

The project was financially supported by King Saud University, Vice Deanship of Research Chairs, Kayyali Chair for Pharmaceutical Industry [Grant no. E-2015].