*1.7.2 Stability enhancement*

Stability study is very important in case of development of new dosage formulation. Stability studies of pharmaceutical co-crystals have several studies such as relative humidity stress, chemical stability, thermal stability, solution stability and photostability study. Lithium drugs have a narrow therapeutic window and are hygroscopic. Lithium co-crystals exhibit modulated pharmacokinetics compared to lithium. The co-crystals of lithium chloride (LIC) and glucose (GLU) were prepared by slow evaporation method and the physical stability of LIC-GLU was compared to lithium chloride at 50% RH and 25°C and through dynamic vapour sorption analysis. LIC-GLU co-crystals improve the physical stability of the solid form of a drug substance with respect to humidity without impacting its pharmacokinetic performance [106]. In adefovir dipivoxil-saccharin co-crystals showed thermodynamic stability at temperatures 40°C and 60°C. The change in the appearance of the samples was also visually examined. The adefovir dipivoxil started to clump together and form a cakelike structure at the first sampling time point at 60°C, whereas adefovir dipivoxilsaccharin co-crystals remained in a powder state [106]. The theophylline-oxalic acid and theophylline-caffeine co-crystals were subjected to relative humidity to check their stability in relation to crystalline theophylline anhydrate. None of the co-crystals in this study converted into a hydrated co-crystal upon storage at high relative humidity (up to 98%). Co-crystals avoid hydrate formation and improvement in the physical stability of the product [107]. Polymorphic changes can also be prevented by using the co-crystallization technique. Lowering the crystal lattice energy and increasing solvation are two mechanisms that increase the solubility of the API in a co-crystal. API solubility can be increased using either technique to varying degrees. Co-crystal solubility in non-polar solvents can be improved through a number of mechanisms, one of which is lowering the crystal lattice energy. Hydrogen bonding, van der Waals forces and electrostatic forces all affect the crystal lattice energy [108].
