title: The effect of PEG molecular weights on the thermal stability and dissolution behaviors of griseofulvin-PEG crystalline inclusion complexes.
abstract: Co-crystals formed between small molecular drugs and hydrophilic co-formers have shown great potential to optimize the dissolution profiles of drug substances. So far most of the co-formers used are small molecules. However, linear polymers are also able to form drug-polymer crystalline inclusion complexes (ICs). In contrast to the small molecular co-formers, molecular weight of the polymer co-formers can be easily changed without disrupting the IC crystal structure, and hence represents an interesting approach to tune the IC properties. In this study, we investigated the effect of PEG molecular weights on the thermal stability and dissolution behavior of Gris-PEG ICs. It was found that the thermal stability of Gris-PEG IC crystals first increased with PEG molecular weight, and then reached a plateau value, while an optimized PEG molecular weight existed for the dissolution profile. The experimental results were explained by the formation of two types of crystal defects during the IC growth in PEG melt: the void defects and the grain boundary defects. This is the first study on the pharmaceutical profiles of drug-polymer crystalline inclusion complexes.
authors.affiliation: Key Laboratory of Advanced Materials (MOE), Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Advanced Materials (MOE), Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Advanced Materials (MOE), Department of Chemical Engineering, Tsinghua University, Beijing 100084, China. Electronic address: yanbin@tsinghua.edu.cn.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Huang
mesh_terms: D003460:Crystallization; D065546:Drug Liberation; D004355:Drug Stability; D006118:Griseofulvin / Q000737:chemistry*; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry*; D013696:Temperature
chemical_list: D006118:Griseofulvin; D011092:Polyethylene Glycols
keywords: Inclusion complex; Insoluble drug; Pharmaceutical co-crystals