ABSTRACT
Two new crystalline polymorphs of the widely used antifungal drug griseofulvin (phases II and III), which originate from the crystallization of the melt, have been detected recently. The crystal structure of phase II of griseofulvin {systematic name: (2S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H,4'H-spiro[1-benzofuran-2,1'-cyclohex-2-ene]-3,4'-dione}, C17H17ClO6, has been solved by powder X-ray diffraction (PXRD). The PXRD pattern of this new phase was recorded at room temperature using synchrotron radiation. The starting structural model was generated by a Monte Carlo simulated annealing method. The final structure was obtained through Rietveld refinement with soft restraints for interatomic bond lengths and angles, except for the aromatic ring, where a rigid-body constraint was applied. The symmetry is orthorhombic (space group P212121) and the asymmetric unit contains two molecules.
Subject(s)
Antifungal Agents/chemistry , Griseofulvin/chemistry , Antifungal Agents/pharmacology , Hydrogen Bonding , Synchrotrons , X-Ray DiffractionABSTRACT
In this paper, we present an investigation of the polymorphism of griseofulvin. In addition to the only reported crystalline form (form I), two new polymorphic forms (II and III) have been identified and characterized by differential scanning calorimetry and powder X-ray diffraction. Reasons why these two polymorphs were isolated during the present study, but not detected during the numerous previous studies on this drug, are also discussed.
Subject(s)
Griseofulvin/chemistry , X-Ray Diffraction/methods , Calorimetry, Differential Scanning/methods , Crystallization , Griseofulvin/analysisABSTRACT
In this paper we present a new protocol to determine faster the solubility of drugs into polymer matrixes. The originality of the method lies in the fact that the equilibrium saturated states are reached by demixing of supersaturated amorphous solid solutions and not by dissolution of crystalline drug into the amorphous polymer matrix as for usual methods. The equilibrium saturated states are thus much faster to reach due to the extra molecular mobility resulting from the strong plasticizing effect associated with the supersaturation conditions. The method is validated using the indomethacin/polyvinylpyrrolidone mixture whose solubility diagram was previously determined by usual techniques. The supersaturated states have been directly obtained in the solid state by comilling, and the investigations have been performed by differential scanning calorimetry and powder X-ray diffraction.
Subject(s)
Polymers/chemistry , Calorimetry , Indomethacin/chemistry , Povidone/chemistry , Solubility , X-Ray DiffractionABSTRACT
An amorphous solid of cyclomaltoheptaose (ß-cyclodextrin, ß-CD) was formed by milling its crystalline form using a high-energy planetary mill at room temperature. The glass transition of this amorphous solid was found to occur above the thermal degradation point of the material preventing its direct observation and thus its full characterization. The corresponding glass transition temperature (T(g)) and the ΔC(p) at T(g) have, however, been estimated by extrapolation of T(g) and ΔC(p) of closely related amorphous compounds. These compounds include methylated ß-CD with different degrees of substitution and molecular alloys obtained by co-milling ß-CD and methylated ß-CD (DS 1.8) at different ratios. The physical characterization of the amorphous states have been performed by powder X-ray diffraction and differential scanning calorimetry, while the chemical integrity of ß-CD upon milling was checked by NMR spectroscopy and mass spectrometry.