Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways

We developed a step-by-step experimental protocol using differential scanning calorimetry (DSC), dynamic vapour sorption (DVS), polarized light microscopy (PLM) and a small-scale dissolution apparatus (μDISS Profiler) to investigate the mechanism (solid-to-solid or solution-mediated) by which crysta...

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Main Authors:	Edueng, Khadijah, Mahlin, Denny, Larsson, Per Olof, Bergström, Christel A.S.
Format:	Article
Language:	English English
Published:	Elsevier B.V. 2017
Subjects:	R Medicine (General) RS Pharmacy and materia medica
Online Access:	http://irep.iium.edu.my/57294/ http://irep.iium.edu.my/57294/ http://irep.iium.edu.my/57294/ http://irep.iium.edu.my/57294/1/57294_Mechanism-based%20selection_new.pdf http://irep.iium.edu.my/57294/2/57294_Mechanism-based%20selection_SCOPUS.pdf

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spelling	iium-572942017-07-18T01:02:08Z http://irep.iium.edu.my/57294/ Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways Edueng, Khadijah Mahlin, Denny Larsson, Per Olof Bergström, Christel A.S. R Medicine (General) RS Pharmacy and materia medica We developed a step-by-step experimental protocol using differential scanning calorimetry (DSC), dynamic vapour sorption (DVS), polarized light microscopy (PLM) and a small-scale dissolution apparatus (μDISS Profiler) to investigate the mechanism (solid-to-solid or solution-mediated) by which crystallization of amorphous drugs occurs upon dissolution. This protocol then guided how to stabilize the amorphous formulation. Indapamide, metolazone, glibenclamide and glipizide were selected as model drugs and HPMC (Pharmacoat 606) and PVP (K30) as stabilizing polymers. Spray-dried amorphous indapamide, metolazone and glibenclamide crystallized via solution-mediated nucleation while glipizide suffered from solid-to-solid crystallization. The addition of 0.001%–0.01% (w/v) HPMC into the dissolution medium successfully prevented the crystallization of supersaturated solutions of indapamide and metolazone whereas it only reduced the crystallization rate for glibenclamide. Amorphous solid dispersion (ASD) formulation of glipizide and PVP K30, at a ratio of 50:50% (w/w) reduced but did not completely eliminate the solid-to-solid crystallization of glipizide even though the overall dissolution rate was enhanced both in the absence and presence of HPMC. Raman spectroscopy indicated the formation of a glipizide polymorph in the dissolution medium with higher solubility than the stable polymorph. As a complementary technique, molecular dynamics (MD) simulations of indapamide and glibenclamide with HPMC was performed. It was revealed that hydrogen bonding patterns of the two drugs with HPMC differed significantly, suggesting that hydrogen bonding may play a role in the greater stabilizing effect on supersaturation of indapamide, compared to glibenclamide Elsevier B.V. 2017-06-28 Article NonPeerReviewed application/pdf en http://irep.iium.edu.my/57294/1/57294_Mechanism-based%20selection_new.pdf application/pdf en http://irep.iium.edu.my/57294/2/57294_Mechanism-based%20selection_SCOPUS.pdf Edueng, Khadijah and Mahlin, Denny and Larsson, Per Olof and Bergström, Christel A.S. (2017) Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways. Journal of Controlled Release, 256. pp. 193-202. ISSN 0168-3659 http://ac.els-cdn.com/S0168365917305345/1-s2.0-S0168365917305345-main.pdf?_tid=67924602-5228-11e7-ae80-00000aab0f6c&acdnat=1497572095_ab01db0b32d121e8baa77db1d9d6ff32 10.1016/j.jconrel.2017.04.015
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English
topic	R Medicine (General) RS Pharmacy and materia medica
spellingShingle	R Medicine (General) RS Pharmacy and materia medica Edueng, Khadijah Mahlin, Denny Larsson, Per Olof Bergström, Christel A.S. Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways
description	We developed a step-by-step experimental protocol using differential scanning calorimetry (DSC), dynamic vapour sorption (DVS), polarized light microscopy (PLM) and a small-scale dissolution apparatus (μDISS Profiler) to investigate the mechanism (solid-to-solid or solution-mediated) by which crystallization of amorphous drugs occurs upon dissolution. This protocol then guided how to stabilize the amorphous formulation. Indapamide, metolazone, glibenclamide and glipizide were selected as model drugs and HPMC (Pharmacoat 606) and PVP (K30) as stabilizing polymers. Spray-dried amorphous indapamide, metolazone and glibenclamide crystallized via solution-mediated nucleation while glipizide suffered from solid-to-solid crystallization. The addition of 0.001%–0.01% (w/v) HPMC into the dissolution medium successfully prevented the crystallization of supersaturated solutions of indapamide and metolazone whereas it only reduced the crystallization rate for glibenclamide. Amorphous solid dispersion (ASD) formulation of glipizide and PVP K30, at a ratio of 50:50% (w/w) reduced but did not completely eliminate the solid-to-solid crystallization of glipizide even though the overall dissolution rate was enhanced both in the absence and presence of HPMC. Raman spectroscopy indicated the formation of a glipizide polymorph in the dissolution medium with higher solubility than the stable polymorph. As a complementary technique, molecular dynamics (MD) simulations of indapamide and glibenclamide with HPMC was performed. It was revealed that hydrogen bonding patterns of the two drugs with HPMC differed significantly, suggesting that hydrogen bonding may play a role in the greater stabilizing effect on supersaturation of indapamide, compared to glibenclamide
format	Article
author	Edueng, Khadijah Mahlin, Denny Larsson, Per Olof Bergström, Christel A.S.
author_facet	Edueng, Khadijah Mahlin, Denny Larsson, Per Olof Bergström, Christel A.S.
author_sort	Edueng, Khadijah
title	Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways
title_short	Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways
title_full	Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways
title_fullStr	Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways
title_full_unstemmed	Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways
title_sort	mechanism-based selection of stabilization strategy for amorphous formulations: insights into crystallization pathways
publisher	Elsevier B.V.
publishDate	2017
url	http://irep.iium.edu.my/57294/ http://irep.iium.edu.my/57294/ http://irep.iium.edu.my/57294/ http://irep.iium.edu.my/57294/1/57294_Mechanism-based%20selection_new.pdf http://irep.iium.edu.my/57294/2/57294_Mechanism-based%20selection_SCOPUS.pdf
first_indexed	2023-09-18T21:20:58Z
last_indexed	2023-09-18T21:20:58Z
_version_	1777411878389022720

Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways

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