A Study On The Preparation Of Ibuprofen Cocrystals

As a supramolecular compound, cocrystal is defined as unit cells comprising anactive pharmacutical ingredient (referred to as API) and a cocrystal former (referredto as CCF), both of which interact by hydrogen bonding and/or any other noncovalentbonds with a fixed stoichiometric ratio. Compared with the pure API, cocrystals mayexhibit some more advantageous physicochemical properties, for example, insolubility, melting point, dissolution rate, stability, etc. Therefore, cocrystals mayenhance the bioavailability and efficacy of APIs.According the crystal engineering principles, the author tries to screen ibuprofencocrystals. Ibuprofen cocrystals are usually prepared by combining ibuprofen andCCF via hydrogen bonding which can be in the form of O–H···O and O–H···Naccording to supramolecular synthon principles. In this paper,12organic compoundswith carboxyl groups (succinic acid, citric acid, L-glutamic acid, L-phenylalanine,L-histidine, L-threonine, lysine and L-arginine) or amide groups (nicotinamide,acetamide, saccharin and salicylamide) were utilized as CCFs to prepare cocrystals.The as-prepared cocrystals were characterized by DSC, PXRD, Raman spectroscopyand single crystal diffraction. Finally, two cocrystals, ibuprofen-nicotinamide andibuprofen-L-arginine, were successfully screened out. The hydrogen bonding of thecocrystals was in the form of O–H···N.The static method was used to measure the solubility of ibuprofen-nicotinamideand ibuprofen-L-arginine in four kinds of solvents (ethanol/water, methanol, ethanoland acetone) from278K-303K. The solubility data was regressed by the Apelblatequation, λh equation and Wilson equation, respectively. The results show that λhequation is the best model for regression of solubility data of ibuprofen-L-arginineand Wilson equation is best one for regression of solubility data of ibuprofen-nicotinamide.Based on the above work, the preparation processes of ibuprofen-L-arginine andibuprofen-nicotinamide cocrystals by solution method were systematically explored.The effects of the operating parameters, such as different solvents, solvent ratio,cooling rate and seeding, on the morphology and size distribution of theibuprofen-L-arginine and ibuprofen-nicotinamide cocrystals were experimentally investigated. Finally, the optimal operation conditions for manufacturing the twococrystals in solution method were determined.