Co-crystals

The main focus of the present study was to explore co-crystallization technique to engineer pharmaceutical co-crystals of poorly aqueous soluble drug- Gliclazide (GLZ) using different GRAS listed coformers; benzoic acid (BA) and itaconic acid (IA). The complexation energy of GLZ and coformers were predicted by Quantum Mechanics method. Co-crystals in 1:2 molar ratios were formulated using solvent evaporation technique using acetone, a class III solvent as a medium for drug and coformer interaction at molecular level. The characteristics of GLZ and resultant co-crystals were evaluated in terms of flowability, drug content uniformity, saturation solubility and in-vitro dissolution studies. Further Fourier transformation infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to identify hydrogen bonding interaction, melting point, crystallinity and surface morphological characteristics of prepared co-crystals respectively. The obtained GLZ co-crystals indicated presence of additional peaks as well as band shifts in the infrared spectrum. Additionally DSC thermograph and XRD confirmed change in crystal lattice. The results of in-vitro dissolution indicated a significant enhancement in the dissolution profiles of both the co-crystals as compared to GLZ. Thus it could be concluded that the co-crystallization technique could be successfully exploited to develop new formulation of GLZ.

The poor aqueous solubility and dissolution rate of API is one of the main challenge in pharmaceutical development. The improvement of solubility and dissolution profiles of these lipophilic drug molecules without altering the molecular structure is a particular challenge for the successful development of pharmaceutical products. Pharmaceutical cocrystals are molecular complexes of an API and one or more cocrystal formers, which are solids at room temperature, interacting through hydrogen bonding, π-stacking or van der Waals forces. A crystalline form of the API is strongly preferred because of their relative ease of isolation, and the physico-chemical stability that the crystalline solid state affords. The vast majority of APIs occur as solids; these include, salts, polymorphs, cocrystals and hydrates/solvates. Cocrystallization as a method of obtaining new forms of Active Pharmaceutical Ingredients (APIs) with improved physicochemical properties like solubility, stability, and melting point has gained much attention in recent years and is a promising alternative to so far employed preparation of salts, hydrates, solvates and other forms. Cocrystallization improves physicochemical properties of drug without affecting their pharmacological properties. There are various methods for preparation of cocrystals like solvent evaporation, solution crystallization, antisolvent addition, kneading etc. The characterization methods includes FTIR, DSC, PXRD, NMR, Raman spectroscopy etc.