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Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition

OBJECTIVES: Polymeric excipients play an important role in a cocrystal formulation to act as precipitation inhibitors to maximize the potential. Otherwise, a stable form of the parent drug will be recrystallized on the dissolving cocrystal surface and/or in the bulk solution during the cocrystal dis...

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Autores principales: Shi, Kejing, Li, Mingzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447287/
https://www.ncbi.nlm.nih.gov/pubmed/37188904
http://dx.doi.org/10.1007/s11095-023-03532-x
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author Shi, Kejing
Li, Mingzhong
author_facet Shi, Kejing
Li, Mingzhong
author_sort Shi, Kejing
collection PubMed
description OBJECTIVES: Polymeric excipients play an important role in a cocrystal formulation to act as precipitation inhibitors to maximize the potential. Otherwise, a stable form of the parent drug will be recrystallized on the dissolving cocrystal surface and/or in the bulk solution during the cocrystal dissolution process, negating the solubility advantage. The objectives of this work were to investigate the potential of using combined polymers to maximise the dissolution performance of surface precipitation pharmaceutical cocrystals. METHODS: The dissolution performance of a highly soluble flufenamic acid and nicotinamide (FFA-NIC) cocrystal has been systematically studied with predissolved or powder mixed with a single polymer, including a surface precipitation inhibitor [i.e., copolymer of vinylpyrrolidone (60%) /vinyl acetate (40%) (PVP-VA)] and two bulk precipitation inhibitors [i.e., polyethylene glycol (PEG) and Soluplus (SLP)], or binary polymers combinations. RESULTS: A single polymer of PVP-VA prevented the FFA surface precipitation for an enhanced dissolution performance of FFA-NIC cocrystal. Unfortunately, it cannot sustain the supersaturated FFA concentration in the bulk solution. A combination of two polymers of PVP-VA and SLP has shown a synergistic inhibition effect to enhance the dissolution advantage of FFA-NIC cocrystal. CONCLUSIONS: The dissolution of a cocrystal with surface precipitation of the parent drug can be described as: i) the cocrystal surface contacting the dissolution medium; ii) the cocrystal surface dissolving; iii) the parent drug precipitation on the dissolving surface; and iv) the parent drug particles redissolving. A combination of two types of polymers can be used to maximise the cocrystal performance in solution. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11095-023-03532-x.
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spelling pubmed-104472872023-08-25 Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition Shi, Kejing Li, Mingzhong Pharm Res Original Research Article OBJECTIVES: Polymeric excipients play an important role in a cocrystal formulation to act as precipitation inhibitors to maximize the potential. Otherwise, a stable form of the parent drug will be recrystallized on the dissolving cocrystal surface and/or in the bulk solution during the cocrystal dissolution process, negating the solubility advantage. The objectives of this work were to investigate the potential of using combined polymers to maximise the dissolution performance of surface precipitation pharmaceutical cocrystals. METHODS: The dissolution performance of a highly soluble flufenamic acid and nicotinamide (FFA-NIC) cocrystal has been systematically studied with predissolved or powder mixed with a single polymer, including a surface precipitation inhibitor [i.e., copolymer of vinylpyrrolidone (60%) /vinyl acetate (40%) (PVP-VA)] and two bulk precipitation inhibitors [i.e., polyethylene glycol (PEG) and Soluplus (SLP)], or binary polymers combinations. RESULTS: A single polymer of PVP-VA prevented the FFA surface precipitation for an enhanced dissolution performance of FFA-NIC cocrystal. Unfortunately, it cannot sustain the supersaturated FFA concentration in the bulk solution. A combination of two polymers of PVP-VA and SLP has shown a synergistic inhibition effect to enhance the dissolution advantage of FFA-NIC cocrystal. CONCLUSIONS: The dissolution of a cocrystal with surface precipitation of the parent drug can be described as: i) the cocrystal surface contacting the dissolution medium; ii) the cocrystal surface dissolving; iii) the parent drug precipitation on the dissolving surface; and iv) the parent drug particles redissolving. A combination of two types of polymers can be used to maximise the cocrystal performance in solution. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11095-023-03532-x. Springer US 2023-05-15 2023 /pmc/articles/PMC10447287/ /pubmed/37188904 http://dx.doi.org/10.1007/s11095-023-03532-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Research Article
Shi, Kejing
Li, Mingzhong
Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition
title Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition
title_full Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition
title_fullStr Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition
title_full_unstemmed Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition
title_short Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition
title_sort optimisation of pharmaceutical cocrystal dissolution performance through a synergistic precipitation inhibition
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447287/
https://www.ncbi.nlm.nih.gov/pubmed/37188904
http://dx.doi.org/10.1007/s11095-023-03532-x
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