Cocrystallizations of EX and MA improved initial dissolution rates compared to the respective original crystals. The mechanism of dissolution enhancement varied. With cocrystal 1, fine particle formation resulted in enhancement, whereas with cocrystal 2, enhancement was due to the maintenance of the cocrystal form and rapid dissolution before transformation to the original crystal.

No abstract

The present study provides a powerful tool to predict dose nonlinearity and will aid in the success of BCS class II drug development.

A slurry crystallization technique was used in cocrystal screening of two nonionizable pharmaceutical host compounds, stanolone and mestanolone, with 11 pharmaceutically acceptable guest acids. Crystallization was performed simply by adding crystallization solvents to solid mixtures of a host and a guest, which had been prepared using lyophilization of their dimethyl sulfoxide solution. Powder X-ray diffraction and thermogravimetric/differential thermal analysis were used to identify new solid forms. Two resultant new forms, stanolone L-tartaric acid 1:1 cocrystal and mestanolone salicylic acid 1:1 cocrystal, were characterized using single-crystal X-ray diffraction. The hosts, despite having the same steroidal skeleton and the same functional groups that form strong hydrogen bonds, each formed a cocrystal with a different guest molecule. All functional groups of the host and guest molecules that form strong hydrogen bonds were engaged in hydrogen bonding, but, despite the highly analogous molecular structures of the hosts, the two cocrystals exhibited dissimilar crystal structures. The present study shows the slurry technique to be viable and practical for cocrystal screening and demonstrates the importance not only of hydrogen bonding but also of geometric fit in cocrystal formation.

Five anhydrous polymorphs (forms I−V) and one hydrate of furosemide−nicotinamide 1:1 cocrystal were discovered, and their solid-state properties were characterized using X-ray powder diffraction and differential scanning calorimetry. The crystal structures of forms I−IV were determined from the X-ray powder diffraction data and showed the structural differences between forms, which are mainly attributable to molecular conformations and supramolecular synthons. The slurry conversion experiments revealed that the order of thermodynamic stability of the polymorphs at 25 °C is I > III > II > V > IV. Dynamic vapor sorption analysis and X-ray single-crystal structure determination of the hydrate were conducted to study the dehydration mechanism. We observed structural similarities between the hydrate and its dehydrate, form IV, such as lattice parameters (except the a-axis length), synthons between furosemide and nicotinamide molecules, and the molecular conformation of furosemide; after dehydration, however, the a-axis contracted and nicotinamide molecules were displaced, along with the pyridine ring twisting.