*3.2.5 Crystallinity and polymorphism*

Polymorphism and crystalline behaviour of solid-state drugs are important for formulators because most of the drugs exist in the solid states and are suitable for the intended use. In a solid state, drugs may exist in salt form, cocrystals, hydrates, polymorphs, amorphous form, solid solutions, and eutectics. Liquid states drugs like valproic acid and general anaesthetics as gaseous phases. In a crystal, lattice atoms are arranged in a unique pattern and they are highly ordered arrangement based on this arrangement they are categorised as crystalline or amorphous. Both forms show different physical and chemical properties, therefore, they have different solubility and stability performances which influence the delivery system and activity of the drug [38].

When the crystalline and amorphous drug substances are analysed and confirmed that they show different X-ray patterns, vapour pressure, melting point, crystal shape, density, hardness, dissolution, solubility, and bioavailable concentration at the site of action. Furthermore, other properties also fluctuate from their standard values for example limited free energy, high melting point and decrease in solubility behaviour can be considered for stable polymorph. A metastable polymorph has a lower melting point, increased solubility, and is more bioavailable than a stable polymorph. Crystals and polymorphs are analysed by advanced techniques such as the X-ray diffraction method, FTIR, NMR, Optical crystallography, hot stage microscopy, SEM/TEM, and differential scanning calorimetry [46, 47]. The polymorphism and crystal habit behaviour affect solubility, for example, anhydrous Carbamazepine has three different polymorphic forms and these forms are different in their physicochemical properties hence, they show different solubility behaviour at different conditions of temperature and melting points. However, the hydrous form of Carbamazepine as such will not have any polymorphic forms. The melting point may also significantly impact the selection of polymorphic forms like most stable form is polymorph III [44].
