Investigation of coated whey protein/alginate beads as sustained release dosage form in simulated gastrointestinal environment

Abstract

Aim: The biopharmaceutical behavior of new formulations based on both food-grade polymers, whey protein (WP) and alginate (ALG) was studied using different in vitro methods. The Biopharmaceutical Classification System (BCS) class I drug Theophylline was chosen as drug model. Method: Drug release was studied (i) at pH 1.2 (2 hours) followed by pH 7.5, and in simulated gastric fluid (SGF; 2 hours) followed by simulated intestinal fluid (SIF) using the paddle method and (ii) in an artificial digestive system. Results: Freeze-dried mixed WP/ALG (62/38) beads were coated with WP or ALG with encapsulation efficiency 34.9% and 18.3%, respectively. At pH 1.2, coated beads exhibited gastroresistant properties (< 10% of drug released after 2 hours) followed at pH 7.5 by a sustained release behavior (< 60% of drug released at 24 hours) controlled by an erosion mechanism. In SGF, despite enzyme hydrolysis, drug release was still controlled due to ALG shrinkage. After transfer in SIF, formulations were completely degraded in less than 2 h with total drug release. In an artificial digestive system, coated beads appeared gastroresistant, intestinal part sustained drug release was controlled by erosion. Conclusion: Combination of in vitro methods allowed prediction of the in vivo potentialities of WP- and ALG- coated WP/ALG beads as oral sustained release systems.

Keywords:

• Alginate
• beads
• controlled release
• in vitro gastrointestinal conditions
• whey proteins

Acknowledgment

This work was supported by the Minister of Foreign and European Affairs of France and the Minister of International Relations of Quebec (60^ème Commission Permanente de Coopération Franco-Québécoise—CPCFQ).