Crystal Engineering of Novel Cocrystals of a Triazole Drug with 1,4-Dicarboxylic Acids

Abstract

Cocrystals of the poorly soluble antifungal drug cis-itraconazole (1) with 1,4-dicarboxylic acids have been prepared. The crystal structure of the succinic acid cocrystal with 1 was determined to be a trimer by single-crystal X-ray. The trimer is comprised of two molecules of 1 oriented in antiparallel fashion to form a pocket with a triazole at either end. The extended succinic acid molecule fills the pocket, bridging the triazole groups through hydrogen-bonding interactions rather than interacting with the more basic piperazine nitrogens. The solubility and dissolution rate of some of the cocrystals are approximately the same as those of the amorphous drug in the commercial formulation and are much higher than those for the crystalline free base. The results suggest that cocrystals of drug molecules have the possibility of achieving the higher oral bioavailability common for amorphous forms of water-insoluble drugs while maintaining the long-term chemical and physical stability that crystal forms provide.

Ibuprofen-Amino Acids Co-Crystal Screening Via Co-Grinding Methods

“…The IR spectrum for 1:1 IBP:PRO (LAG) (Fig. 3) shows peaks at 1634.42 cm -1 for C=C stretching, 1711.30 cm -1 for -C=O in carboxylic acid, 1981.36 cm -1 for C-H vibration in R-CH=CH 2 , 2553.95 cm -1 for -OH in carboxylic acid, 2868.40 cm -1 and 2953.81 cm -1 for -CH 3 . This results show that there are no proton transfer activity for this 1:1 IBP:PRO from LAG method.…”

“…Not limited to solubility, co-crystal also helps in improving other physicochemical properties such as stability, dissolution, and bioavailability of poorly water soluble drugs [3]. The properties of drug co-crystal can be modified by forming pharmaceutical co-crystals that usually has two compounds which are single API and a relevant co-crystal former (CCF).…”

From form to function: Crystallization of active pharmaceutical ingredients

“…Solvates and hydrates are typically excluded from this list. Such crystal forms could offer advantages in terms of bioavailability, 18,19 stability, and the ability to extend the product portfolio if sufficient advantages can be demonstrated by developing the cocrystal compared to the neutral form.…”

The Elusive Structural Origin of Plastic Bending in Dimethyl Sulfone Crystals with Quasi‐isotropic Crystal Packing

“…The quest for novel organic compounds that can substitute for inorganic materials has motivated material chemists to explore the physical properties of organic solids.A mong the various properties,t he mechanical behavior of organic crystals has gained considerable attention recently.A part from the fact that mechanical properties are directly relevant to several aspects of solid state sciences [1] (such as formulation of drugs in the pharmaceutical industry [2] and devising organic functional materials [3] ), these properties point to certain fundamental structural connections with the nature and strength of the interactions between molecules in the crystals. While most organic crystals are known to be brittle,n ewer examples of crystals that exhibit plastic and elastic bending are being discovered.…”