1: Pharmazie. 2007 Jul;62(7):499-504. Prediction of drug solubility in amphiphilic di-block copolymer micelles: the role of polymer-drug compatibility. Latere Dwan'Isa JP, Rouxhet L, Préat V, Brewster ME, Ariën A. Johnson & Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Pharmaceutical Sciences, Beerse, Belgium. 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. PMID: 17718189 [PubMed - indexed for MEDLINE] Related Links Spontaneously self-assembled micelles from poly(ethylene glycol)-b-poly(epsilon-caprolactone-co-trimethylene carbonate) for drug solubilization. [Pharmazie. 2008] PMID:18444514 Biodegradable self-assembling PEG-copolymer as vehicle for poorly water-soluble drugs. [Pharm Res. 2004] PMID:15497683 Solubilization of hydrophobic drugs by methoxy poly(ethylene glycol)-block-polycaprolactone diblock copolymer micelles: theoretical and experimental data and correlations. [J Pharm Sci. 2008] PMID:17683080 Encapsulation of amphotericin B in poly(ethylene glycol)-block-poly(epsilon-caprolactone-co-trimethylenecarbonate) polymeric micelles. [Int J Pharm. 2006] PMID:16406402 Self-assembling PEG-p(CL-co-TMC) copolymers for oral delivery of poorly water-soluble drugs: a case study with risperidone. [J Control Release. 2005] PMID:15681087