title: Prediction of drug solubility in amphiphilic di-block copolymer micelles: the role of polymer-drug compatibility.
abstract: The goal of the current study was to assess the value of predictive computational approaches for estimating drug solubility in hydrated micelles formed from di-block copolymers of polyethylene glycol (PEG) and random copolyesters of epsilon-caprolactone (CL) and trimethylene carbonate (TMC) using drug-polymer compatibility as assessed through the Flory-Huggins interaction parameter (chi). In order to accomplish this, the compatibility of several well-known model drugs (associated with the four biopharmaceutics classification system (BCS) classes) was assessed with both segments of the amphiphilic di-block copolymer PEG-b-P(CL-co-TMC). Compatibilities were estimated based on the Hansen modification of the Hildebrand approach using Molecular Modeling Pro software. Experimental solubilities for model drugs were determined using a shake-flask technique at various polymer concentrations. The solubilities of 8 compounds in 10% w/v micelle solutions were in relatively good agreement with the predicted drug-polymer compatibility. In addition, the approach allows for the selection of a suitable di-block copolymer for optimal solubilization of a specific drug. Furosemide was assessed as a model with results suggesting that it can be best entrapped in a di-block copolyester containing a relatively high CL content. The data suggests that prediction of drug solubilization of block copolymer-based micelles may be facilitated by assessing the compatibility of the drug for the component polymeric domains.
authors: Johnson & Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Pharmaceutical Sciences, Beerse, Belgium.
authors: J P
authors: JP
authors: Latere Dwan'Isa
authors: L
authors: L
authors: Rouxhet
authors: V
authors: V
authors: Préat
authors: M E
authors: ME
authors: Brewster
authors: A
authors: A
authors: Ariën
mesh_terms: D000465:Algorithms; D002208:Caproates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004146:Dioxanes / Q000737:chemistry*; D004232:Diuretics / Q000737:chemistry; D004344:Drug Incompatibility; D005665:Furosemide / Q000737:chemistry; D007783:Lactones / Q000737:chemistry*; D008823:Micelles; D008956:Models, Chemical; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers; D012995:Solubility
chemical_list: D002208:Caproates; D004146:Dioxanes; D004232:Diuretics; D007783:Lactones; D008823:Micelles; D011108:Polymers; D011092:Polyethylene Glycols; C443643:trimethylene carbonate; C121056:caprolactone; D005665:Furosemide