Novel Polymorph of Favipiravir-An Antiviral Medication

被引：23

作者：

Goloveshkin, Alexander S. ^{[1
]}

Korlyukov, Alexander A. ^{[1
,2
]}

Vologzhanina, Anna V. ^{[1
]}

机构：

[1] Russian Acad Sci, AN Nesmeyanov Inst Organoelement Cpds, 28 Vavilova Str, Moscow 119991, Russia

[2] DM Mendeleev Univ Chem Technol Russia, Higher Chem Coll, Russian Acad Sci, Miusskaya Sq 9, Moscow 125047, Russia

来源：

PHARMACEUTICS | 2021年 / 13卷 / 02期

基金：

俄罗斯科学基金会;

关键词：

active pharmaceutical ingredient; quantum theory “ atoms in molecules” polymorphism; powder X-ray diffraction; periodic density functional theory calculations; INITIO MOLECULAR-DYNAMICS; TOTAL-ENERGY CALCULATIONS; HYDROGEN-BOND; CRYSTAL-STRUCTURES; SOLID-STATE; TOPOLOGICAL ANALYSIS; PATTERNS; CONTACTS; MODEL; SALTS;

D O I：

10.3390/pharmaceutics13020139

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Various solid forms of pharmaceutically important compounds exhibit different physical properties and bioactivity; thus, knowledge of the structural landscape and prediction of spontaneous polymorph transformations for an active pharmaceutical ingredient is of practical value for the pharmaceutical industry. By recrystallization from ethyl acetate, a novel polymorph of 6-fluoro-3-hydroxypyrazine-2-carboxamide (trademark favipiravir, RNA polymerase inhibitor) was obtained and characterized using differential scanning calorimetry (DSC), infra-red spectroscopy and powder X-ray diffraction (XRD) analysis. The favipiravir molecule in two polymorphs realizes similar H-bonding motifs, but the overall H-bonded networks differ. Based on periodic density functional theory calculations, the novel tetragonal polymorph with two interpenetrated H-bonded networks is slightly less stable than the orthorhombic one with the zst topology of the underlying H-bonded net that is in accord with experimentally observed powder XRD patterns of slow conversion of the tetragonal phase to the orthorhombic one. However, topological analysis of net relations revealed that no transformations can be applied to convert H-bonded networks in the experimental unit cells, and DSC data indicate no solid-state reactions at heating.

引用

页码：1 / 14

页数：14

共 58 条

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