The Nateglinide Polymorphs Study

The medicine's curative efect relies on their characters, purity, dosage, production procedures, the dosage form, the moment and so on. With the development of science and technology, it has been affirmed that the polymorphic of drug substances is the other one major reason which affect drug dissolution, chemical stability, as well as drug bioavailability. Even a small amount of contamination of polymorphs and amorphous form may alter its physicochemical properties of the original drug substances. The process of medicine preparation often involves selection of the polymorphism, so it is very important to study them for clinical effect and safety in synthesis and formulation processes.Nateglinide is a novel drug designed for the treatment of type II diabetes. Type II diabetes is the most common form of diabetes and it occurs in people of all ages and races. In type II diabetes,either the body does not produce enough insulin or the cell ignore the insulin. Nateglinide is a novel oral hypoglycemic agent for the management of type II diabetes. The drug has a rapid onset of action short half-life, and short duration of action. When administered prior to a meal, nateglinide restores phrase I insulin secretion, which is lost in type II diabetes.By some means such as recrystallization,freeze-drying etc,we make the X2-form and amorphous of nateglinide. Their structures was characterized by X-ray powder diffraction, high performance liquid chromatography, elemental analysis and differential scanning calorimetry, their structures are different from that of known B-form, H-form and S-form, we make sure that the X2-form and amorphous of nateglinide are new crystal structures of nateglinide.We can see that the surface topography of amorphous of nateglinide which maked by freeze-drying is columned structure with hollow, and its specific surface area is double times of a column.We have adopt the methods of the crystal form transformation such as different solvent, different temperature and grinding to investigate the polymorphism and the crystal form transformation of Nategelinde. And finding that the H-form nateglinide can be transformed to X2-form ,X2-form can be transformed to B-form, (H-form ,X2-form and B-form) be transformed to S-form, (H-form, S-form and B-form) be transformed to Amorphous , and we had established the condition of their transformation.The solubility values of H,B,S,Amorphous and X2 forms of nateglinide have been measured at different temperatures, and the enthalpy has been calculated. The solubility value from high to low is Amorphous>X2>H>S >B. The enthalpies of H, B, S, Amorphous and X2 forms are 28.44 KJ/mol,42.84 KJ/mol ,29.14 KJ/mol,23.09 KJ/mol,28.29 KJ/mol and 29.51 KJ/mol, respectively.