Solubility enhancement of poorly water soluble domperidone by complexation with the large ring cyclodextrin.

The water solubility of domperidone (DMP) could be improved by complexation with large ring cyclodextrins (LR-CDs). LR-CDs contain a relatively hydrophobic cavity that is capable of entrapping the molecules to form inclusion complexes. The complex formation capability of mixture LR-CDs having a degree of polymerization (DP) of 22-48, with DMP was investigated. The phase solubility profile of mixture LR-CD/DMP was classified as AN-type, resulting in increased DMP solubility in water by 3-fold. Various physicochemical techniques confirmed the mixture LR-CD/DMP complex formation. Single LR-CD with DP of 26, 27, 28, 29, 30, 33 and 34 (CD26 ~ CD34) were isolated from LR-CD mixtures using ODS column for HPLC separation. The CD33/DMP complex has demonstrated the most significant improvement compared to other single LR-CD complexes with a 2.7-fold increase in DMP solubility. The molecular dynamic result revealed that DMP formed stable complexes with CD33 by positioned fully encapsulated inside the cavity and covered by 13-14 subunits of CD33.