Terahertz and Raman Spectroscopic Investigation of Monohydrate Cocrystal of Antitubercular Isoniazid with Protocatechuic Acid

Pharmaceutical cocrystal provides an alternative modification strategy for the formulation development of drugs owning to their potential ability to improve the physicochemical properties of active pharmaceutical ingredients (APIs) efficiently by changing inter-molecular interactions between raw materials. Isoniazid (INH) is an indispensable main drug for the treatment of tuberculosis, but its tablet formulation is unstable and prone to degradation. In the present study, the monohydrate cocrystal of INH and protocatechuic acid (PA) was prepared by solvent evaporation using PA as cocrystal former to optimize the properties of INH. The parent materials and corresponding 1:1 molar ratio INH-PA monohydrate cocrystal have been characterized by the terahertz time-domain (THz-TDS) and Raman spectroscopy. The THz absorption spectra displayed that there were obvious differences between the peaks of experimental cocrystal and the parent materials, and the same situation was found in Raman vibrational spectra. In addition, density functional theory (DFT) was applied to simulating and optimizing the structure of INH-PA monohydrate cocrystal and supplied corresponding vibrational modes. Our results provided a unique method to characterize the formation of INH-PA monohydrate cocrystal at the molecular-level and a lot of information about cocrystal structure and intra-molecular and/or inter-molecular hydrogen bond interactions in the emerging pharmaceutical cocrystal fields.

Urea as a Cocrystal Former—Study of 3 Urea Based Pharmaceutical Cocrystals

Cocrystallization is commonly used for its ability to improve the physical properties of APIs, such as solubility, bioavailability, compressibility, etc. The pharmaceutical industry is particularly interested in those cocrystals comprising a GRAS former in connection with the target API. In this work, we focus on the potential of urea as a cocrystal former, identifying three novel pharmaceutical cocrystal systems with catechin, 3-hydroxyl-2-naphthoic and ellagic acid. Interestingly, the stability of catechin under high humidity or high temperature environment is improved upon cocrystallization with urea. Moreover, the solubility of ellagic acid is improved about 17 times. This work displays the latent possibility of urea in improving the physical property of drug molecules using a cocrystallization approach.

New insight in improving solubility of poorly soluble drugs by preventing the formation of their hydrogen-bonds: a case of dapsone salts with camphorsulfonic and 5-sulfosalicylic acid

Improving the solubility of poorly soluble drug has always been a challenging subject in the field of medicine. In this regard, the pharmaceutical cocrystal strategy has been considered an effective...

Pharmaceutical Cocrystal Development of TAK-020 with Enhanced Oral Absorption

The objective of this study was to improve the solubility of poorly water-soluble drugs by pharmaceutical cocrystal engineering techniques and select the best pharmaceutical forms with high solubility and solubilized formulations for progress from the early discovery stage toward the clinical stage. Several pharmaceutical cocrystals of TAK-020, a Bruton tyrosine kinase inhibitor, were newly discovered in the screening based on the solid grinding method and the slurry method, considering thermodynamic factors that dominate cocrystal formation. TAK-020/gentisic acid cocrystal (TAK-020/GA CC) was selected based on a physicochemical property of enhanced dissolution rate. TAK-020/GA CC was proven to be a reliable cocrystal formation with a definitive stoichiometric ratio by a variety of analytical techniques—pKa calculation, solid-state nuclear magnetic resonance, and single X-ray structure analysis from the view of regulation. Furthermore, its absorption was remarkable and beyond those achieved in currently existing solubilized formulation techniques, such as nanocrystal, amorphous solid dispersion, and lipid-based formulation, in dog pharmacokinetic studies. TAK-020/GA CC was the best drug form, which might lead to good pharmacological effects with regard to enhanced absorption and development by physicochemical characterization. Through the trials of solid-state optimization from early drug discovery to pharmaceutical drug development, the cocrystals can be an effective option for achieving solubilization applicable in the pharmaceutical industry.