Physical characterization of picotamide monohydrate and anhydrous picotamide

Picotamide is an antiplatelet agent given by mouth as monohydrate (PICOW) (Plactidil) in thrombo-embolic disorders. This study deals with physical characterization of PICOW recrystallized from various solvents and the respective dehydration products using X-ray powder diffractometry (XRD), infrared spectroscopy (IR), and thermal analytical techniques (differential scanning calorimetry, DSC; thermogravimetric analysis, TGA; simultaneous TGA/DSC; hot stage microscopy, HSM). Monophasic and biphasic DSC and TGA profiles of water loss were recorded under open conditions for PICOW samples which showed the same monoclinic crystal structure. Biphasic profiles became monophasic for gently ground samples which were, however, structurally identical to the intact samples. Morphological factors, the various degree of “perfection” of the PICOW crystal lattice, and/or cluster aggregation of PICOW crystals were assumed to be responsible for the differing dehydration patterns. Polymorphism in anhydrous
picotamide, i.e., nucleation of crystal forms A, mp 135.5 ± 0.4 °C, and B, mp 152.9 ± 0.3 °C after dehydration of PICOW, was detected by DSC and HSM. The dehydration product of PICOW under isothermal conditions (115 °C, 20 mmHg), PICOA, was mainly composed of the lower melting polymorph A (fusion enthalpy 74.4 ± 2.2 J g-1), which gradually reverted to the starting hydrate by storing in an ambient atmosphere. Dissolution tests of PICOW and PICOA
in water at 37 °C as both powders and compressed disks reflected to some extent the higher solubility of the metastable form (by 24% at 37 °C) in terms of both higher dissolution efficiency and percent of active ingredient dissolved (by 28%) and intrinsic dissolution rate (by 32%).