title: Solid-state amorphization of rebamipide and investigation on solubility and stability of the amorphous form.
abstract: Solid-state amorphization of crystalline rebamipide (RBM) was realized by ball milling and spray drying. The amorphous content of samples milled for various time was quantified using X-ray powder diffraction. Crystalline RBM and three amorphous RBM obtained by milling and spray drying were characterized by morphological analysis, X-ray diffraction, thermal analysis and vibrational spectroscopy. The crystal structure of RBM was first determined by single-crystal X-ray diffraction. In addition, the solubility and dissolution rate of the RBM samples were investigated in different media. Results indicated that the solubility and the dissolution rates of spray-dried RBM-PVP in different media were highly improved compared with crystalline RBM. The physical stabilities of the three amorphous RBM were systematically investigated, and the stability orders under different storage temperatures and levels of relative humidity (RH) were both as follows: spray dried RBM < milled RBM < spray dried RBM-PVP. A direct glass-to-crystal transformation was induced under high RH, and the transformation rate rose with increasing RH. However, amorphous RBM could stay stable at RH levels lower than 57.6% (25 °C).
authors.affiliation: a College of Chemical Engineering, Sichuan University , Chengdu , China.
authors.forename: Xinnuo
authors.initials: X
authors.lastname: Xiong
authors.affiliation: a College of Chemical Engineering, Sichuan University , Chengdu , China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
authors.affiliation: a College of Chemical Engineering, Sichuan University , Chengdu , China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: a College of Chemical Engineering, Sichuan University , Chengdu , China.
authors.forename: Peixiao
authors.initials: P
authors.lastname: Tang
authors.affiliation: a College of Chemical Engineering, Sichuan University , Chengdu , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: a College of Chemical Engineering, Sichuan University , Chengdu , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003890:Desiccation; D004355:Drug Stability; D011205:Povidone / Q000737:chemistry*; D011208:Powders; D015363:Quinolones / Q000737:chemistry*; D012995:Solubility; D000069453:Ultrasonic Waves; D014961:X-Ray Diffraction
chemical_list: D011208:Powders; D015363:Quinolones; D011205:Povidone; C052785:rebamipide; D000409:Alanine
keywords: Rebamipide; amorphous; dissolution rate; milling; quantification; solubility; spray drying; stability