Characterization of the Polymorphic Behavior of an Organic Compound Using a Dynamic Thermal and X-ray Powder Diffraction Technique

Abstract

The crystalline polymorphic forms of several samples of an organic compound produced by Dowpharma were characterized using differential scanning calorimetry (DSC); X-ray powder diffraction (XRPD); combined, simultaneous, and dynamic differential scanning calorimetry/X-ray powder diffraction (DSC/XRPD); and high performance liquid chromatography (HPLC). A total of 10 crystalline polymorphs were identified, six of which are anhydrous. Form l is a heptahydrate that reversibly converts to anhydrous Form I under dry conditions and also undergoes a reversible solid-solid phase transition at about 110 °C to convert to Form II. Form Il is anhydrous and melts at approximately 220 °C. Form III crystallizes as a hexahydrate, which reversibly converts to the monohydrate Form III and then to an anhydrous Form III above 120 °C. Anhydrous Form III melts at approximately 200 °C. Form IV crystallized as a hydrous material, which was converted to the anhydrous Form IV above approximately 60 °C, in a reversible process. Form IV appears to be unstable in high humidity conditions (e.g., 90% relative humidity at 25 °C) and slowly converts to Forms I and III. Form IV also undergoes a nonreversible solid-solid phase transition at approximately 180 °C, to form anhydrous Form V. Form V melts at approximately 245 °C. Form VI is observed only in the anhydrous state and melts at approximately 245 °C. The anhydrous nature of Form VI makes this material the most ideal crystalline material for subsequent formulation work.

Pentamorphs of Acedapsone

“…Polymorphs can be easily distinguished by their unique X-ray diffraction . The calculated X-ray line patterns from the single crystal structures (Figure a) exhibit signature peaks at 2θ = 10.99°, 14.72°, 16.30°, 18.53 °, and 25.27° for Form I, and at 17.53°, 19.75 °, 21.47°, and 22.08° for Form II.…”

Crystallization and physicochemical investigation of melevodopa hydrochloride, a commercially available antiparkinsonian active substance

“…Polymorphism may also include solvation or hydration products (also known as solvatomorphism) and amorphous forms". Only the imagination limits the possibilities of polymorph screening, among which the crystallization by evaporation/cooling from a proper solvent/solvent mixtures (14), crystallization from supercritical fluid (15), exposure to vapour at high or low relative humidity (16), solid-state polymorphic transformation (17) and seeding/pseudoseeding (18). The polymorphs can modify the stability, solubility, and manufacturing properties.…”

A new polymorph of glipizide with enhanced properties obtained using environmentally friendly methods

“…XRPD analysis is a standard technique used to distinguish the solid forms of a drug. 21 The XRPD patterns (X'Pert PRO diffractometer (PANalytical), Cu Kα radiation (λ = 1.5406 Å)) of Forms I and III show one strong diffraction peak in each case (Fig. 2a).…”