posted on 2016-11-23, 00:00authored byZhi Zhong, Xiaotong Yang, Bao-hua Guo, Jun Xu, Yanbin Huang
Multicomponent
crystals provide a promising strategy to modulate
and optimize the dissolution behaviors of drugs, among which pharmaceutical
cocrystals formed between drugs and small molecular coformers have
received much attention. Recent studies have shown that certain drugs
can also form crystalline inclusion complexes (ICs) with linear polymers,
representing a new subcategory of multicomponent pharmaceutical crystals.
In this study, we investigated in detail the dissolution behavior
and the structure evolution of a crystalline inclusion complex formed
by the drug diflunisal (DIF) and hydrophobic poly(ε-caprolactone)
(PCL). The dissolution profiles of DIF–PCL IC exhibited decreased
solubility and dissolution rate compared with the pure DIF crystals
at a low pH value. The PCL chains initially residing in the IC channels
coalesced and formed crystalline but porous PCL shells on the IC particles
during dissolution. These results demonstrated the possibility of
using drug–PCL ICs to slow down the drug dissolution, and the
in situ formation of an interesting core–shell structure with
a biodegradable PCL shell and a drug–PCL IC core.