No abstract

Cocrystals are an emerging class of crystalline materials composed of two or more different molecules in the same crystal lattice that are physically connected by non-ionic and non-covalent bonds. Formulating...

The aim of this study was to design and evaluate a cocrystal capable of releasing a highly water soluble drug, isoniazid (INH), over a period of longer than several hours by forming a cocrystal with curcumin (CUR). The 2:1 INH-CUR cocrystal can not only lower the dissolution rate of INH but also exhibit potential therapeutic synergy. A phase-pure INH-CUR cocrystal was obtained by rapid solvent removal above a threshold evaporation rate. The formation of an INH-CUR cocrystal was confirmed by powder X-ray diffraction and the construction of a temperature–composition phase diagram with differential scanning calorimetry. The pharmaceutical properties of the INH-CUR cocrystal, including hygroscopicity, stability, and dissolution performance, were compared to those of INH and CUR. Extended release of INH from the cocrystal was observed in both pH 1.2 and 6.8 buffers, while their release patterns behaved differently. The dissolution kinetics of INH-CUR cocrystal followed Fickian diffusion and was controlled by the cocrystal solubility and the mode of CUR recrystallization. At pH 1.2, a significant amount of CUR form III precipitated and recrystallized onto the surface of undissolved cocrystals after 4 h and thus substantially inhibited the INH release from cocrystals thereafter. On the other hand, ∼90% of INH was released linearly at pH 6.8 in the first 18 h, and complete release of INH was attained at 24 h. This work demonstrated that cocrystallization is a promising formulation strategy for achieving up to 48 h of drug release without using polymers.

Cocrystallization represents an emerging approach to tackle the issues associated with pharmaceutical product performance and processing, owing to its capability of modifying a variety of physicochemical properties. In this study, we sought to modify the crystal form of itraconazole (ITZ) with suberic acid (SUB) via rapid solvent removal methods, namely rotary evaporation and spray drying. A phase pure ITZ-SUB cocrystal, which could not be obtained by traditional cocrystallization methods, was successfully prepared by rotary evaporation. The new cocrystal was confirmed by powder X-ray diffraction, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. Spray drying was further employed for particle engineering of ITZ-SUB to achieve optimal pulmonary delivery. By manipulating the critical processing parameters, inhalable ITZ-SUB agglomerates with a mass median aerodynamic diameter of 2.56 ± 2.27 μm and fine particle fraction of 64.10% w/w were reproducibly prepared. The inhalable powders contained mainly coamorphous ITZ-SUB, while a small portion of cocrystals still exists. Compared with the raw ITZ, the intrinsic dissolution rate of the ITZ-SUB cocrystal was ∼39 times faster, and a significantly larger fraction of ITZ-SUB agglomerates was dissolved after 180 min of the test. Besides, both products remained stable after 1-month storage at 60 °C.