Warfarin Sodium Stability in Oral Formulations

Warfarin sodium is a low-dose pharmaceutical blood thinner that exists in two forms: the clathrate form and the amorphous form. In commercially available warfarin sodium oral suspension, the active pharmaceutical ingredient (API) is added in the amorphous state. This study investigates the apparent...

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Autores principales:	Evangelia Dimitrokalli, Stefani Fertaki, Michail Lykouras, Petros Kokkinos, Malvina Orkoula, Christos Kontoyannis
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	warfarin sodium amorphous warfarin warfarin clathrate oral suspension crystallization Raman spectroscopy Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/b9548879404946e290e272bf017a5432
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spelling	oai:doaj.org-article:b9548879404946e290e272bf017a54322021-11-11T18:36:06ZWarfarin Sodium Stability in Oral Formulations10.3390/molecules262166311420-3049https://doaj.org/article/b9548879404946e290e272bf017a54322021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6631https://doaj.org/toc/1420-3049Warfarin sodium is a low-dose pharmaceutical blood thinner that exists in two forms: the clathrate form and the amorphous form. In commercially available warfarin sodium oral suspension, the active pharmaceutical ingredient (API) is added in the amorphous state. This study investigates the apparent instability of the commercially available warfarin liquid oral formulation using Raman and IR spectroscopy, X-ray diffraction, differential scanning calorimetry, UV spectroscopy, and optical microscopy. Warfarin, not its sodium salt, was identified as the undissolved solid existing in the suspension. This was found to be due to the dissociation of sodium salt and the protonation of the warfarin ion in the liquid phase, which triggered the crystallization of the sparingly soluble unsalted form. The coexistence of protonated and unprotonated warfarin ions in the supernatant, as detected by Raman and UV spectroscopy, confirmed this assumption. Study of the dissolution of warfarin sodium amorphous salt and crystalline sodium clathrate in the placebo and pure water verified the results. The effect of pH and temperature on warfarin precipitation was also explored.Evangelia DimitrokalliStefani FertakiMichail LykourasPetros KokkinosMalvina OrkoulaChristos KontoyannisMDPI AGarticlewarfarin sodium amorphouswarfarinwarfarin clathrateoral suspensioncrystallizationRaman spectroscopyOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6631, p 6631 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	warfarin sodium amorphous warfarin warfarin clathrate oral suspension crystallization Raman spectroscopy Organic chemistry QD241-441
spellingShingle	warfarin sodium amorphous warfarin warfarin clathrate oral suspension crystallization Raman spectroscopy Organic chemistry QD241-441 Evangelia Dimitrokalli Stefani Fertaki Michail Lykouras Petros Kokkinos Malvina Orkoula Christos Kontoyannis Warfarin Sodium Stability in Oral Formulations
description	Warfarin sodium is a low-dose pharmaceutical blood thinner that exists in two forms: the clathrate form and the amorphous form. In commercially available warfarin sodium oral suspension, the active pharmaceutical ingredient (API) is added in the amorphous state. This study investigates the apparent instability of the commercially available warfarin liquid oral formulation using Raman and IR spectroscopy, X-ray diffraction, differential scanning calorimetry, UV spectroscopy, and optical microscopy. Warfarin, not its sodium salt, was identified as the undissolved solid existing in the suspension. This was found to be due to the dissociation of sodium salt and the protonation of the warfarin ion in the liquid phase, which triggered the crystallization of the sparingly soluble unsalted form. The coexistence of protonated and unprotonated warfarin ions in the supernatant, as detected by Raman and UV spectroscopy, confirmed this assumption. Study of the dissolution of warfarin sodium amorphous salt and crystalline sodium clathrate in the placebo and pure water verified the results. The effect of pH and temperature on warfarin precipitation was also explored.
format	article
author	Evangelia Dimitrokalli Stefani Fertaki Michail Lykouras Petros Kokkinos Malvina Orkoula Christos Kontoyannis
author_facet	Evangelia Dimitrokalli Stefani Fertaki Michail Lykouras Petros Kokkinos Malvina Orkoula Christos Kontoyannis
author_sort	Evangelia Dimitrokalli
title	Warfarin Sodium Stability in Oral Formulations
title_short	Warfarin Sodium Stability in Oral Formulations
title_full	Warfarin Sodium Stability in Oral Formulations
title_fullStr	Warfarin Sodium Stability in Oral Formulations
title_full_unstemmed	Warfarin Sodium Stability in Oral Formulations
title_sort	warfarin sodium stability in oral formulations
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b9548879404946e290e272bf017a5432
work_keys_str_mv	AT evangeliadimitrokalli warfarinsodiumstabilityinoralformulations AT stefanifertaki warfarinsodiumstabilityinoralformulations AT michaillykouras warfarinsodiumstabilityinoralformulations AT petroskokkinos warfarinsodiumstabilityinoralformulations AT malvinaorkoula warfarinsodiumstabilityinoralformulations AT christoskontoyannis warfarinsodiumstabilityinoralformulations
_version_	1718431783642464256

Warfarin Sodium Stability in Oral Formulations

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