title: Thermally-prepared polymorphic forms of cilostazol.
abstract: Prior to this study, cilostazol, an antithrombotic drug, was thought to exist as a single crystalline phase with a melting point of approximately 159 degrees C (Form A). On cooling, melts often form a glass that, when heated, may crystallize as additional crystalline polymorphic forms. Cilostazol, when reheated, subsequently forms polymorphs that melt at approximately 136 degrees C (Form B) and 146 degrees C (Form C). Free-energy temperature diagrams estimated from calorimetry data reveal that each pair of the cilostazol polymorphs (A-B, B-C, and A-C) is monotropic. Essentially pure samples of suitable crystalline shape and size permitted single crystal structural analysis of Forms A and C. Theoretical solubility ratios calculated using calorimetry data indicate that at 37 degrees C, Form B should be more than four times more soluble and Form C should be more than two times more soluble than Form A. Forms B and C could not be crystallized from solvents. Metastable forms from super cooled melts analyzed by intrinsic dissolution and Fourier transform-Raman experiments demonstrated that Forms B and C undergo a rapid, solvent-mediated recrystallization to Form A, making dissolution rate measurements difficult.
authors.affiliation: aaiResearch, Inc., 2320 Scientific Park Drive, Wilmington, North Carolina 28405, USA.
authors.forename: Grayson W
authors.initials: GW
authors.lastname: Stowell
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Behme
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Denton
authors.forename: Inigo
authors.initials: I
authors.lastname: Pfeiffer
authors.forename: Frederick D
authors.initials: FD
authors.lastname: Sancilio
authors.forename: Linda B
authors.initials: LB
authors.lastname: Whittall
authors.forename: Robert R
authors.initials: RR
authors.lastname: Whittle
mesh_terms: D002151:Calorimetry / Q000379:methods; D002626:Chemistry, Pharmaceutical; D000077407:Cilostazol; D004055:Differential Thermal Analysis / Q000379:methods; D006358:Hot Temperature; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D013777:Tetrazoles; D000077407:Cilostazol