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de Koninck P.,Center Biomedical | Archambault D.,University of Quebec at Montréal | Archambault D.,University of Montréal | Hamel F.,Center Biomedical | And 2 more authors.
Journal of Pharmacy and Pharmaceutical Sciences | Year: 2010

Purpose. The aim of this study was to develop a formulation for bioactive compounds using Carboxymethyl Starch (CMS) as excipient containing protease inhibitors. This formulation provided gastroprotection of peptidic bioactive agents afforded by CMS excipient and enhanced stability against pancreatic enzymes by coformulated inhibitors of proteolysis. Such stability is needed for formulation of oral vaccines with specific antigens. Methods. CMS was synthesized by treatment of starch with monochloroacetic acid in conditions leading to a substitution degree of about 1 meq/g and used as excipient for monolithic devices (300 mg tablets). Pefabloc SC and Aprotinin inhibitors were tested in dissolution media and in formulation to prevent the degradation of released bioactive materials. To evaluate the structural integrity and biological stability of plant proteins in the CMS formulation, albumin and lipase were added to the plant protein extract as protein and enzyme markers respectively. The amount of released and recovered proteins was evaluated by SDS-PAGE and densitometric analysis. Results. Release kinetics and protein stability of our alfalfa protein extract (APE) in simulated gastric fluid (SGF) with pepsin and in simulated intestinal fluid (SIF) with pancreatin allowed us to evaluate the capacity of our formulations to protect peptide active agents against acidity and proteolysis. It was found that 1.6% (w/w) of Pefabloc SC provides 98% protection of the released plant proteins for formulations of 30% APE with CMS. In addition, when bovine serum albumin (BSA) was added to the plant protein extract as a marker, 90% protection of the released BSA was observed. Furthermore, a much higher lipase activity was found in the releasing media when the formulations contained Pefabloc SC. Conclusion. Formulations with CM-Starch excipients and containing protease inhibitors prevents protein degradation and protect lipase activity, showing a marked potential to use for orally administered bioactive peptides and therapeutic enzymes.

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