Solid-State Phase Transformation of Monohydrate and Anhydrous Form II of Sitagliptin Phosphate into a Novel Anhydrous Form IV - Solvent-Driven, Temperature-Induced and Stress Testings.

Autor:	Chachorovska M; Research and Development, Alkaloid AD, Bul. Aleksandar Makedonski 12, 1000 Skopje, North Macedonia. Electronic address: mchachorovska@alkaloid.com.mk., Lefton JB; Department of Chemistry, Southern Methodist University, 231 Fondren Science Building, Dallas, TX 75275, USA., Petrushevski G; Quality Control, Alkaloid AD, Blvd. Aleksandar Makedonski 12, 1000, Skopje, Republic of North Macedonia; Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Arhimedova 5, 1000 Skopje, North Macedonia., Geskovski N; Institute of Pharmaceutical Technology, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, North Macedonia., Jakimovska V; Research and Development, Alkaloid AD, Bul. Aleksandar Makedonski 12, 1000 Skopje, North Macedonia., Makreski P; Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Arhimedova 5, 1000 Skopje, North Macedonia. Electronic address: petremak@pmf.ukim.mk.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2024 Feb; Vol. 113 (2), pp. 396-406. Date of Electronic Publication: 2023 Nov 14.
DOI:	10.1016/j.xphs.2023.11.007
Abstrakt:	The solid form landscape of sitagliptin phosphate was systematically evaluated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and X-ray powder diffraction (XRPD), supported by a plethora of auxiliary analytical techniques. The preformulation experiments resulted in the transition of sitagliptin phosphate monohydrate into a new anhydrous form (designated as form IV), obtained after recrystallization from absolute ethanol. The anhydrous form IV remained stable under stressed conditions (1 month at 25 °C/60 %RH and 40 °C/75 %RH). On the other hand, thermal heating (dehydration) of sitagliptin phosphate monohydrate resulted in conversion into another anhydrous form II. Form II was found to be metastable, because after melting, under exposure at 40 °C/75 %RH for 1 month, or when dissolved in absolute ethanol converted to the stable anhydrous form IV of sitagliptin phosphate. A monotropic relationship was found between both studied anhydrous forms. Intrinsic dissolution tests revealed differences in the dissolution rates between the monohydrate and the anhydrous forms of sitagliptin phosphate. This research corrects the record with an accurate chemical composition of the anhydrous form IV of sitagliptin phosphate that was previously regarded as a hemiethanolate. In addition, the crystal structure of anhydrous form II of sitagliptin phosphate has been solved and reported for the first time. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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