Aerosil as a novel co-crystal co-former for improving the dissolution rate of hydrochlorothiazide

Co-crystallization of drugs with benign co-formers is promising for enhancing dissolution rate of poorly soluble drugs. The selection of safe and pharmacologically inert co-formers is a critical step in this process. Accordingly, the objective of this work was to investigate aerosil 200 as a potential co-former for the preparation of hydrochlorothiazide co-crystal. Co-crystal formation involved acetone assisted co-grinding after mixing hydrochlorothiazide with increasing molar ratios of aerosil (1:1, 1:2 and 1:4). The prepared formulations were subjected to Fourier transform infrared spectroscopy, differential thermal analysis, and powder X-ray diffraction studies. These investigations provided evidence for co-crystal formation between the drug and aerosil. Complete co-crystallization was even achieved at the lowest tested concentration of aerosil suggesting that the stoichiometric ratio of co-crystal formation is 1:1 molar ratio. The dissolution studies revealed faster dissolution rate of the drug from co-crystals compared to the pure unprocessed drug or that which was subjected to wet grinding in absence of aerosil. Increasing the molar ratio of aerosil increased the amount dissolved in the first 5 min. This may be attributed to adsorption of the formed co-crystal on the surface of excess aerosil. In conclusion, aerosil can be considered as co-crystal co-former with potential future application.