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Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments

Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolid...

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Autores principales: Paisana, Maria, Wahl, Martin, Pinto, João
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332009/
https://www.ncbi.nlm.nih.gov/pubmed/26703534
http://dx.doi.org/10.3390/molecules201219832
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author Paisana, Maria
Wahl, Martin
Pinto, João
author_facet Paisana, Maria
Wahl, Martin
Pinto, João
author_sort Paisana, Maria
collection PubMed
description Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolidone) in forming pellets by wet extrusion and spheronisation. Anhydrous olanzapine was added to water with or without those polymers prior to extrusion with microcrystalline cellulose. Assessment of olanzapine conversion was made by XRP-Diffraction; FTIR spectroscopy; calorimetry (DSC) and microscopy (SEM for crystal size and shape). The addition of water converted the anhydrous form into dihydrate B and higher hydrate; whereas polyethyleneglycol promoted a selective hydrate conversion into the higher hydrate olanzapine form. Both polyvinylpyrrolidone and hydroxypropylcellulose prevented the hydrate transformations of the anhydrous drug; the latter even in the presence of hydrate seeds. This may be explained by the higher H-bond ability; higher network association and higher hydrophobicity of hydroxypropylcellulose by comparison with polyethyleneglycol and polyvinylpyrrolidone; which could contribute to its higher affinity to the crystal surfaces of the hydrate nuclei/initial crystals and promoting steric hindrance to the incorporation of other drug molecules into the crystal lattice; thus, preventing the crystal growth. The addition of microcrystalline cellulose needed for the pellets production (final product) did not eliminate the protector effect of both hydroxypropylcellulose and polyvinylpyrrolidone during pellets’ processing and dissolution evaluation.
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spelling pubmed-63320092019-01-24 Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments Paisana, Maria Wahl, Martin Pinto, João Molecules Article Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolidone) in forming pellets by wet extrusion and spheronisation. Anhydrous olanzapine was added to water with or without those polymers prior to extrusion with microcrystalline cellulose. Assessment of olanzapine conversion was made by XRP-Diffraction; FTIR spectroscopy; calorimetry (DSC) and microscopy (SEM for crystal size and shape). The addition of water converted the anhydrous form into dihydrate B and higher hydrate; whereas polyethyleneglycol promoted a selective hydrate conversion into the higher hydrate olanzapine form. Both polyvinylpyrrolidone and hydroxypropylcellulose prevented the hydrate transformations of the anhydrous drug; the latter even in the presence of hydrate seeds. This may be explained by the higher H-bond ability; higher network association and higher hydrophobicity of hydroxypropylcellulose by comparison with polyethyleneglycol and polyvinylpyrrolidone; which could contribute to its higher affinity to the crystal surfaces of the hydrate nuclei/initial crystals and promoting steric hindrance to the incorporation of other drug molecules into the crystal lattice; thus, preventing the crystal growth. The addition of microcrystalline cellulose needed for the pellets production (final product) did not eliminate the protector effect of both hydroxypropylcellulose and polyvinylpyrrolidone during pellets’ processing and dissolution evaluation. MDPI 2015-12-14 /pmc/articles/PMC6332009/ /pubmed/26703534 http://dx.doi.org/10.3390/molecules201219832 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Paisana, Maria
Wahl, Martin
Pinto, João
Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments
title Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments
title_full Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments
title_fullStr Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments
title_full_unstemmed Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments
title_short Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments
title_sort role of polymeric excipients in the stabilization of olanzapine when exposed to aqueous environments
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332009/
https://www.ncbi.nlm.nih.gov/pubmed/26703534
http://dx.doi.org/10.3390/molecules201219832
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