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


METHODS
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.


CONCLUSIONS
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.
Université Clermont1, UFR Pharmacie, Centre de Recherche en Nutrition Humaine, Equipe de Recherche Technologique Conception, Ingénierie et Développement de l'Aliment et du Médicament, Clermont-Ferrand, France.
Géraldine
G
Hébrard
Valérie
V
Hoffart
Jean-Michel
JM
Cardot
Muriel
M
Subirade
Monique
M
Alric
Eric
E
Beyssac
D000464:Alginates / Q000737:chemistry*; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D008894:Milk Proteins / Q000737:chemistry*; D053758:Nanoparticles; D010316:Particle Size; D019999:Pharmaceutical Solutions; D012015:Reference Standards; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000067816:Whey Proteins
D000464:Alginates; D003692:Delayed-Action Preparations; D005079:Excipients; D008894:Milk Proteins; D019999:Pharmaceutical Solutions; D014665:Vasodilator Agents; D000067816:Whey Proteins; D013806:Theophylline