title: PLGA in situ implants formed by phase inversion: critical physicochemical parameters to modulate drug release.
abstract: In situ forming implants (ISI) based on phase separation by solvent exchange represent an attractive alternative to conventional preformed implants and microparticles for parenteral applications. They are indeed easier to manufacture and their administration does not require surgery, therefore improving patient compliance. They consist of polymeric solutions precipitating at the site of injection and thus forming a drug eluting depot. Drug release from ISI is typically divided into three phases: burst during precipitation of the depot, diffusion of drug through the polymeric matrix and finally drug release by system degradation. This review gives a comprehensive overview on (i) the theoretical bases of these three phases, (ii) the parameters influencing them and (iii) the remaining drawbacks which have to be addressed to enlarge their commercial opportunities. Indeed, although some of them are already commercialized, ISI still suffer from limitations: mainly lack of reproducibility in depot shape, burst during solidification and potential toxicity. Nevertheless, depending on the targeted therapeutic application, these shortcomings may be transformed into advantages. As a result, keys are given in order to tailor these formulations in view of the desired application so that ISI could gain further clinical importance in the following years.
authors.affiliation: Université de Lorraine, CITHÉFOR, EA 3452, Faculté de Pharmacie, BP 80403, F-54000 Nancy Cedex, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Parent
authors.affiliation: Université de Lorraine, Laboratoire de Chimie Physique Macromoléculaire (LCPM), FRE 3564, ENSIC, BP 20451, F-54000 Nancy Cedex, France; Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Physique Macromoléculaire (LCPM), FRE 3564, ENSIC, BP 20451, F-54000 Nancy Cedex, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Nouvel
authors.affiliation: Freie Universität Berlin, College of Pharmacy, Kelchstraße 31, 12169 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Koerber
authors.affiliation: Université de Lorraine, CITHÉFOR, EA 3452, Faculté de Pharmacie, BP 80403, F-54000 Nancy Cedex, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Sapin
authors.affiliation: Université de Lorraine, CITHÉFOR, EA 3452, Faculté de Pharmacie, BP 80403, F-54000 Nancy Cedex, France. Electronic address: philippe.maincent@univ-lorraine.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maincent
authors.affiliation: Université de Lorraine, CITHÉFOR, EA 3452, Faculté de Pharmacie, BP 80403, F-54000 Nancy Cedex, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Boudier
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D044367:Phase Transition; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019736:Prostheses and Implants
chemical_list: D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: 2-pyrrolidone; 2P; BA; BB; DMSO; Drug delivery system; EA; GA; GRAS; IIG; ISI; ISM; In situ forming implants; In situ precipitation; LA; LD50; N-methyl-2-pyrrolidone; NMP; PDLA; PEO; PGA; PLA; PLGA; PLLA; PPO; PVP; Phase separation; Solvent exchange; TA; benzyl alcohol; benzyl benzoate; dimethyl sulfoxide; ethyl acetate; generally recognized as safe; glycolide; in situ forming implants; in situ forming microparticles; inactive ingredient; lactide; lethal dose 50; poly(d,l-lactide); poly(ethylene oxide); poly(glycolide); poly(l-lactide); poly(lactide); poly(lactide-co-glycolide); poly(propylene oxide); polyvinylpyrrolidone; triacetin