The guest polymer effect on the dissolution of drug-polymer crystalline inclusion complexes.

Abstract

A drug–polymer crystalline inclusion complex (IC) is a novel solid form of drug, in which drug molecules form parallel channels, and linear polymer chains reside in these channels. In this study, we used carbamazepine (CBZ) as a model drug, and directly studied the effect of different types of guest polymers on the dissolution properties of drug–polymer ICs. We successfully prepared ICs formed from CBZ with hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(ε-caprolactone) (PCL), respectively, and confirmed that these two drug–polymer ICs both had the same channel-type crystal structure as CBZ form II. During the dissolution test, CBZ–PEG IC showed a faster dissolution rate compared to CBZ form II under both sink and non-sink conditions. CBZ–PCL IC was confirmed to be more stable in aqueous medium, as the guest polymer PCL delayed its transformation to less-soluble crystals during dissolution.