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...

Recent advances in crystal engineering by cocrystallization have offered a promising approach for tackling undesirable physicochemical properties of drug substances. In this study, various structurally similar benezenediols and benezenetriols, namely, catechol (CAT), resorcinol (RES), hydroquinone (HYQ), hydroxyquinol (HXQ), and pyrogallol (PYR), were employed as coformers to obtain phase pure cocrystals with curcumin (CUR) by rapid solvent evaporation of solutions. We successfully prepared two new cocrystals, CUR–CAT and CUR–HYQ, and a new polymorph of cocrystal, CUR–HXQ. Both could not be obtained by traditional cocrystallization methods. Their 1:1 stoichiometry was confirmed by the construction of a binary phase diagram through differential scanning calorimetry analysis. The hygroscopicity, dissolution, and tableting performance of the resulting cocrystals were evaluated. Compared to the individual constituent coformers, cocrystals exhibited profound improvement in the stability against high humidity. The CUR–HXQ cocrystal displayed an intrinsic dissolution rate 7 times faster than CUR. Four out of the five cocrystals had better tabletability. This work demonstrated the effectiveness of discovering cocrystals by kinetic entrapment using a fast solvent removal approach. Some of these cocrystals possess improved pharmaceutical properties for future development of solid dosage forms of CUR.

Retinal diseases, such as age-related macular degeneration and diabetic retinopathy, are the leading causes of blindness worldwide. The mainstay of treatment for these blinding diseases remains to be surgery, and the available pharmaceutical therapies on the market are limited, partially owing to various biological barriers in hindering the delivery of therapeutics to the retina. The nanoparticulate drug delivery system confers the capability for delivering therapeutics to the specific ocular targets and, hence, potentially revolutionizes the current treatment landscape of retinal diseases. While the research to date indicates the enormous therapeutics potentials of the nanoparticulate delivery systems, the successful translation of these systems from the bench to bedside is challenging and requires a combined understanding of retinal pathology, physiology of the eye, and particle and formulation designs of nanoparticles. To this end, the review begins with an overview of the most prevalent retinal diseases and related pharmacotherapy. Highlights of the current challenges encountered in ocular drug delivery for each administration route are provided, followed by critical appraisal of various nanoparticulate drug delivery systems for the retinal diseases, including their formulation designs, therapeutic merits, limitations, and future direction. It is believed that a greater understanding of the nano-biointeraction in eyes will lead to the development of more sophisticated drug delivery systems for retinal diseases.

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.