SITAGLIPTIN HYDROCHLORIDE POLYMORPHIC FORMS
Publication Date: 2016-Mar-18
The IP.com Prior Art Database
This disclosure relates to cystalline and amorphous sitagliptin hydrochloride polymorphic forms.
Sitagliptin dihydrogen phosphate, chemically named as (2R)-4-oxo-4-[3-(trifluoro- methyl)-5,6-dihydro[l,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-l-(2,4,5-trifluorophenyl)butan-2-amine dihydrogen phosphate, is an oral antihyperglycemic of the dipeptidyl peptidase-IV (DPP-IV) inhibitor class. Inhibition of DPP-IV, an enzyme that inactivates both glucose- dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-I), represents a recent approach to the treatment and prevention of type-2 diabetes, also known as non- insulin dependent diabetes mellitus (NIDDM). Sitagliptin also has an effect on appetite as it slows down gastric motility and induces a feeling of satiety. This reduction of appetite can help patients to lose weight which is also a useful effect in patients with diabetes.
Sitagliptin exists in different salts and the present disclosure relates to sitagliptin hydrochloride crystalline and amorphous forms.
Example 1: Preparation of an amorphous hydrate of sitagliptin hydrochloride
Sitagliptin hydrochloride (100 g) was dissolved in water (100 mL) at 50°C, reaction mass was filtered on micron filter and distilled water at below 50 °C under vacuum. Unload the wet material and dried at 65-70°C to get an amorphous hydrate of sitagliptin hydrochloride. Yields 97 %, water content 2-4 % W/W and by powder X-ray diffraction, see Figure 1.
Example 2: Preparation of an amorphous hydrate of sitagliptin hydrochloride
Sitagliptin free base (100 g) was dissolved in acetone (400 mL) at 35°C, reaction mass was filtered on micron filter and adjusted the pH to 2.0-3.5 with CP hydrochloride, distilled of solvent at below 50°C under vacuum. Unload the wet material and dried at 65-70°C...