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]

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