DSPindex guides dose selection to extend drug supersaturation lifetime during cocrystal dissolution.

Newman, LM; Kavanagh, ON; Machado, TC

DSPindex guides dose selection to extend drug supersaturation lifetime during cocrystal dissolution.

Newman, LM Kavanagh, ON Machado, TC

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Publisher:: ELSEVIER
Publication Type:: Journal Article
Citation:: Int J Pharm, 2025, 671, pp. 125298
Issue Date:: 2025-02-25

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Field	Value	Language
dc.contributor.author	Newman, LM
dc.contributor.author	Kavanagh, ON
dc.contributor.author	Machado, TC
dc.date.accessioned	2026-02-18T03:57:43Z
dc.date.available	2025-01-27
dc.date.available	2026-02-18T03:57:43Z
dc.date.issued	2025-02-25
dc.identifier.citation	Int J Pharm, 2025, 671, pp. 125298
dc.identifier.issn	0378-5173
dc.identifier.issn	1873-3476
dc.identifier.uri	http://hdl.handle.net/10453/193568
dc.description.abstract	Synchronising both cocrystal dissolution and drug precipitation processes is the key for the development of cocrystal systems with desired dissolution-supersaturation-precipitation (DSP) behaviours. Our findings with ketoconazole (KTZ) - p-aminobenzoic acid (PABA) 1:1 cocrystal show that this can be achieved by generating non-stoichiometric coformer concentrations that allow us to modulate the maximum theoretical cocrystal supersaturation SA (thermodynamic limit) below the drug critical supersaturation σcrit (kinetic limit). The application of our conceptual graphical approach combined with the two metrics SA and the DSPindex answer the question of how much additional coformer is needed to target optimal sustained drug supersaturation levels. Modulating SA < σcrit and DSPindex > 1 allowed for a stable and sustained KTZ release system with supersaturation levels of 6 by 24 h. Findings provide a direct approach for better early decisions regarding cocrystal dose design and/or coformer concentration to be added to formulations to ultimately fine-tune drug supersaturation by coupling dissolution and precipitation processes.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	ELSEVIER
dc.relation.ispartof	Int J Pharm
dc.relation.isbasedon	10.1016/j.ijpharm.2025.125298
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	Pharmacology & Pharmacy
dc.subject.classification	3214 Pharmacology and pharmaceutical sciences
dc.subject.mesh	Crystallization
dc.subject.mesh	Solubility
dc.subject.mesh	Ketoconazole
dc.subject.mesh	Drug Liberation
dc.subject.mesh	4-Aminobenzoic Acid
dc.subject.mesh	Chemistry, Pharmaceutical
dc.subject.mesh	Delayed-Action Preparations
dc.subject.mesh	Chemical Precipitation
dc.subject.mesh	Thermodynamics
dc.subject.mesh	4-Aminobenzoic Acid
dc.subject.mesh	Ketoconazole
dc.subject.mesh	Delayed-Action Preparations
dc.subject.mesh	Crystallization
dc.subject.mesh	Chemistry, Pharmaceutical
dc.subject.mesh	Solubility
dc.subject.mesh	Thermodynamics
dc.subject.mesh	Chemical Precipitation
dc.subject.mesh	Drug Liberation
dc.subject.mesh	Crystallization
dc.subject.mesh	Solubility
dc.subject.mesh	Ketoconazole
dc.subject.mesh	Drug Liberation
dc.subject.mesh	4-Aminobenzoic Acid
dc.subject.mesh	Chemistry, Pharmaceutical
dc.subject.mesh	Delayed-Action Preparations
dc.subject.mesh	Chemical Precipitation
dc.subject.mesh	Thermodynamics
dc.title	DSPindex guides dose selection to extend drug supersaturation lifetime during cocrystal dissolution.
dc.type	Journal Article
utslib.citation.volume	671
utslib.location.activity	Netherlands
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2026-02-18T03:57:39Z
pubs.publication-status	Published
pubs.volume	671

Abstract:

Synchronising both cocrystal dissolution and drug precipitation processes is the key for the development of cocrystal systems with desired dissolution-supersaturation-precipitation (DSP) behaviours. Our findings with ketoconazole (KTZ) - p-aminobenzoic acid (PABA) 1:1 cocrystal show that this can be achieved by generating non-stoichiometric coformer concentrations that allow us to modulate the maximum theoretical cocrystal supersaturation SA (thermodynamic limit) below the drug critical supersaturation σcrit (kinetic limit). The application of our conceptual graphical approach combined with the two metrics SA and the DSPindex answer the question of how much additional coformer is needed to target optimal sustained drug supersaturation levels. Modulating SA < σcrit and DSPindex > 1 allowed for a stable and sustained KTZ release system with supersaturation levels of 6 by 24 h. Findings provide a direct approach for better early decisions regarding cocrystal dose design and/or coformer concentration to be added to formulations to ultimately fine-tune drug supersaturation by coupling dissolution and precipitation processes.

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http://hdl.handle.net/10453/193568