Hassana Hsein1, Ghislain Garrait1, Fahima Tamani1, Eric Beyssac2, Valérie Hoffart1. 1. Univ Clermont 1, UFR Pharmacie, EA4678, Laboratoire de Biopharmacie, Clermont-Ferrand, F-63001, France. 2. Univ Clermont 1, UFR Pharmacie, EA4678, Laboratoire de Biopharmacie, Clermont-Ferrand, F-63001, France. eric.beyssac@udamail.fr.
Abstract
PURPOSE: In earlier study, we proposed denatured whey protein (DWP) powder obtained by atomization as a new excipient to promote oral drug delivery. In this work, we evaluate the possibility to formulate tablets based on DWP powders and to characterize their role as a matrix mucoadhesive excipient. METHODS: Tablets containing increased amount of DWP (10 to 30%) were produced by direct compression after mixing with theophylline, microcrystalline cellulose, Aerosil® and magnesium stearate. Dissolution behaviors of obtained tablets were evaluated in different USP buffers (pH 1.2, 4.5 and 6.8) and in simulated gastric and intestinal fluids and mechanisms analyzed by multiple mathematical models. Swelling, erosion and mucoadhesion were also evaluated. Finally, release and absorption were studied in the artificial digestive system (TIM 1). RESULTS: Tablets based on DWP and containing 300 mg of theophylline were obtained by direct compression. These tablets exhibited controlled release driven by diffusion starting from 15% DWP content whatever the pH studied. They also showed a great extent of swelling and water uptake while matrix weight loss was limited. Addition of enzymes accelerated drug release which became governed by erosion according to Peppas model. CONCLUSIONS: The present study shows that DWP powders can be successfully used as a pharmaceutical excipient, and in particular as a matrix mucoadhesive controlled release tablets.
PURPOSE: In earlier study, we proposed denatured whey protein (DWP) powder obtained by atomization as a new excipient to promote oral drug delivery. In this work, we evaluate the possibility to formulate tablets based on DWP powders and to characterize their role as a matrix mucoadhesive excipient. METHODS: Tablets containing increased amount of DWP (10 to 30%) were produced by direct compression after mixing with theophylline, microcrystalline cellulose, Aerosil® and magnesium stearate. Dissolution behaviors of obtained tablets were evaluated in different USP buffers (pH 1.2, 4.5 and 6.8) and in simulated gastric and intestinal fluids and mechanisms analyzed by multiple mathematical models. Swelling, erosion and mucoadhesion were also evaluated. Finally, release and absorption were studied in the artificial digestive system (TIM 1). RESULTS: Tablets based on DWP and containing 300 mg of theophylline were obtained by direct compression. These tablets exhibited controlled release driven by diffusion starting from 15% DWP content whatever the pH studied. They also showed a great extent of swelling and water uptake while matrix weight loss was limited. Addition of enzymes accelerated drug release which became governed by erosion according to Peppas model. CONCLUSIONS: The present study shows that DWP powders can be successfully used as a pharmaceutical excipient, and in particular as a matrix mucoadhesive controlled release tablets.
Authors: Juan Domínguez-Robles; Sarah A Stewart; Andreas Rendl; Zoilo González; Ryan F Donnelly; Eneko Larrañeta Journal: Biomolecules Date: 2019-08-28