caa a22 4500 477126340 CHVBK 20180405111650.0 cr unu---uuuuu 170330e19970701xx s 000 0 eng 10.1023/A:1012147700014 doi (NATIONALLICENCE)springer-10.1023/A:1012147700014 Improved Activity of a New Angiotensin Receptor Antagonist by an Injectable Spray-Dried Polymer Microsphere Preparation [Elektronische Daten] [François-Xavier Lacasse, Patrice Hildgen, Jacqueline Pérodin, Emmanuel Escher, Nigel Phillips, Jean McMullen] Purpose. To characterize and evaluate in vitro and in vivo the release mechanisms involved in spray-dried biodegradable microspheres having differents Poly(D,L-lactide) blend formulations and containing an antihypertensive drug (L-158,809). Methods. Microspheres and blended polymers were characterized by DSC, SEM, confocal laser microspcopy and size analysis. In vitro release studies were evaluated by using microspheres made from various blends of high and low molecular weight polymer. In vivo studies were evaluated by L-158,809 antagonist ATI function versus the shift of the normal dose-response curve of blood pressure induced by Angio-tensine II. Results. The average yield of L-158,809 microspheres (10% (w/w)) was 95% of the theoritical loading. The average diameter of the microspheres was from 1 to 3 micrometers. In all release experiments, a significant burst effect (< 15%) was observed followed by a near zero-order release kinetics. In vivo studies with two different formulations show a strong shift of angiotensin II dose-response curve. Conclusions. The release kinetics and photomicrographs suggest that the system is best described as a multi-parameter controlled released system in which the drug is molecularly dispersed. In vivo results demonstrating the controlled release of L-158,809. Plenum Publishing Corporation, 1997 microspheres nationallicence spray-drying nationallicence polymer blend nationallicence polylactic acid nationallicence L-158-809 nationallicence Lacasse François-Xavier Faculty of Pharmacy, University of Montréal, Montréal, Québec, Canada aut Hildgen Patrice Faculty of Pharmacy, University of Montréal, Montréal, Québec, Canada aut Pérodin Jacqueline Department of Pharmacology, University of Sherbrooke, Québec, Canada aut Escher Emmanuel Department of Pharmacology, University of Sherbrooke, Québec, Canada aut Phillips Nigel Faculty of Pharmacy, University of Montréal, Montréal, Québec, Canada aut McMullen Jean Faculty of Pharmacy, University of Montréal, Montréal, Québec, Canada aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/7(1997-07-01), 887-891 0724-8741 14:7<887 1997 14 11095 https://doi.org/10.1023/A:1012147700014 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012147700014 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lacasse François-Xavier Faculty of Pharmacy, University of Montréal, Montréal, Québec, Canada aut NATIONALLICENCE 700 1- Hildgen Patrice Faculty of Pharmacy, University of Montréal, Montréal, Québec, Canada aut NATIONALLICENCE 700 1- Pérodin Jacqueline Department of Pharmacology, University of Sherbrooke, Québec, Canada aut NATIONALLICENCE 700 1- Escher Emmanuel Department of Pharmacology, University of Sherbrooke, Québec, Canada aut NATIONALLICENCE 700 1- Phillips Nigel Faculty of Pharmacy, University of Montréal, Montréal, Québec, Canada aut NATIONALLICENCE 700 1- McMullen Jean Faculty of Pharmacy, University of Montréal, Montréal, Québec, Canada aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/7(1997-07-01), 887-891 0724-8741 14:7<887 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer