title: Inclusion of acitretin into cyclodextrins: phase solubility, photostability, and physicochemical characterization.
abstract: Acitretin, a retinoid for the treatment of severe psoriasis, exhibits extremely low aqueous solubility and high photosensitivity. This study investigated the effects of the complexation of acitretin with the respective hydroxypropyl-beta-cyclodextrin (HPBCD) and randomly substituted methyl-beta-cyclodextrin (RMBCD) on the aqueous solubility and photostability of the drug. Phase-Solubility studies indicated that the solubility of acitretin was dramatically improved by formation of complexes and further increased by pH adjustment. Stability constants were much higher for acitretin complexed with RMBCD than with HPBCD. Both cyclodextrins acted to decrease degradation of acitretin in solution. The physicochemical properties of solid inclusion complexes were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry. Molecular modeling with MMFF94s force field (SYBYL V6.6) was utilized to predict the preferred orientation of acitretin in the cyclodextrin cavity and the main structural features responsible for the enhancement of its solubility and photostability.
authors: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543.
authors: Xin
authors: X
authors: Liu
authors: Hai-Shu
authors: HS
authors: Lin
authors: J C
authors: JC
authors: Thenmozhiyal
authors: Sui Yung
authors: SY
authors: Chan
authors: Paul C
authors: PC
authors: Ho
mesh_terms: D017255:Acitretin / Q000032:analysis / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003505:Cyclodextrins / Q000032:analysis / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D008029:Lighting / Q000009:adverse effects*; D012995:Solubility
chemical_list: D003505:Cyclodextrins; D017255:Acitretin