title: Influence of formulation composition and process on the characteristics and in vitro release from PLGA-based sustained release injectables.
abstract: Understanding and controlling the in vitro release behavior of a formulation is a first step toward rationalized selection of a solubility enhancing formulation strategy with a desired release profile in vivo. Therefore six model formulations, representing three different formulation strategies, were physicochemically analyzed and their in vitro release was determined. Solid dispersions based on a PLGA/PVP matrix were compared to solid dispersions in a pure PLGA matrix. Additionally these solid dispersion strategies were compared to the strategy of particle size reduction by means of an API microsuspension. Depending on composition and manufacturing method, formulations varied in particle size, porosity, phase behavior, surface coverage and physical state of the API. This resulted in observed differences in their in vitro release profile. For the various formulation strategies tested both a porous PLGA-based formulation and PLGA/PVP-based formulations, resulted in vitro in sustained release of the poorly soluble API with over 50% of drug released after 24h. For PLGA-based formulations the porosity was identified as a critical parameter influencing in vitro drug release. For the PLGA/PVP-based formulations the release rate can be tailored by the amount of PLGA present. Particle size reduction resulted in immediate total drug release.
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Joke
authors.initials: J
authors.lastname: Meeus
authors.affiliation: Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Scurr
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Appeltans
authors.affiliation: Pharmaceutical Companies of Johnson & Johnson, Janssen, Discovery Sciences, PD&S_PDM, Beerse, Belgium.
authors.forename: Katie
authors.initials: K
authors.lastname: Amssoms
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Annaert
authors.affiliation: Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham, United Kingdom.
authors.forename: Martyn C
authors.initials: MC
authors.lastname: Davies
authors.affiliation: Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham, United Kingdom.
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Roberts
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium. Electronic address: guy.vandenmooter@pharm.kuleuven.be.
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D007267:Injections; D019344:Lactic Acid / Q000737:chemistry*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D016062:Porosity; D011759:Pyrrolidines / Q000737:chemistry; D012995:Solubility
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D011108:Polymers; D011145:Polyvinyls; D011759:Pyrrolidines; C505150:poly(N-vinylpyrrolidine); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Controlled release; Dissolution; MDSC; Microspheres; PLGA; PVP; Solid dispersions; Surface analysis; ToF-SIMS