In-situ freeze-drying - forming amorphous solids directly within capsules: An investigation of dissolution enhancement for a poorly soluble drug

Abstract Conversion into the amorphous form enhances the dissolution of poorly soluble drugs, however the barrier to market for medicines containing an amorphous drug is poor stability. The aim was to produce the amorphous form of a drug within a capsule, without thermal or mechanical stress during...

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Autores principales:	Abdulmalik Alqurshi, K. L. Andrew. Chan, Paul G. Royall
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b04b9d75e534878a545ee15a0cbf2e0
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spelling	oai:doaj.org-article:4b04b9d75e534878a545ee15a0cbf2e02021-12-02T15:18:54ZIn-situ freeze-drying - forming amorphous solids directly within capsules: An investigation of dissolution enhancement for a poorly soluble drug10.1038/s41598-017-02676-22045-2322https://doaj.org/article/4b04b9d75e534878a545ee15a0cbf2e02017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02676-2https://doaj.org/toc/2045-2322Abstract Conversion into the amorphous form enhances the dissolution of poorly soluble drugs, however the barrier to market for medicines containing an amorphous drug is poor stability. The aim was to produce the amorphous form of a drug within a capsule, without thermal or mechanical stress during manufacture. To facilitate this aim, the mechanism for drug-polymer interaction was explored. Nifedipine and polyvinylpyrrolidone were dissolved in tert-butanol at different drug/polymer ratios. These solutions were dispensed into gelatin capsules and freeze-dried. Differential scanning calorimetry (DSC) & novel FT-IR analysis based on peak symmetry measurements confirmed the absence of crystallinity when polyvinylpyrrolidone exceeded 50%w/w. Capsules containing 10 mg of nifedipine were amorphous and stable for over 3 months at ≈40 °C. Evidence of hydrogen bonding between the N-H group of nifedipine and the C=O group of PVP was observed and this interaction inhibited nifedipine crystallisation. PVP’s high affinity for water and the nifedipine-polymer interaction lead to a significant dissolution rate enhancement. The freeze-dried capsule, 10%w/w nifedipine/PVP, had the highest dissolution rate constant of 0.37 ± 0.05 min−1, and the lowest time to achieve 50% dissolution or t1/2 of 1.88 ± 0.05 min. This formulation reached 80% dissolved in less than 6 min whereas the equivalent marketed liquid filled nifedipine capsule took 3 times longer to reach 80% dissolution.Abdulmalik AlqurshiK. L. Andrew. ChanPaul G. RoyallNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abdulmalik Alqurshi K. L. Andrew. Chan Paul G. Royall In-situ freeze-drying - forming amorphous solids directly within capsules: An investigation of dissolution enhancement for a poorly soluble drug
description	Abstract Conversion into the amorphous form enhances the dissolution of poorly soluble drugs, however the barrier to market for medicines containing an amorphous drug is poor stability. The aim was to produce the amorphous form of a drug within a capsule, without thermal or mechanical stress during manufacture. To facilitate this aim, the mechanism for drug-polymer interaction was explored. Nifedipine and polyvinylpyrrolidone were dissolved in tert-butanol at different drug/polymer ratios. These solutions were dispensed into gelatin capsules and freeze-dried. Differential scanning calorimetry (DSC) & novel FT-IR analysis based on peak symmetry measurements confirmed the absence of crystallinity when polyvinylpyrrolidone exceeded 50%w/w. Capsules containing 10 mg of nifedipine were amorphous and stable for over 3 months at ≈40 °C. Evidence of hydrogen bonding between the N-H group of nifedipine and the C=O group of PVP was observed and this interaction inhibited nifedipine crystallisation. PVP’s high affinity for water and the nifedipine-polymer interaction lead to a significant dissolution rate enhancement. The freeze-dried capsule, 10%w/w nifedipine/PVP, had the highest dissolution rate constant of 0.37 ± 0.05 min−1, and the lowest time to achieve 50% dissolution or t1/2 of 1.88 ± 0.05 min. This formulation reached 80% dissolved in less than 6 min whereas the equivalent marketed liquid filled nifedipine capsule took 3 times longer to reach 80% dissolution.
format	article
author	Abdulmalik Alqurshi K. L. Andrew. Chan Paul G. Royall
author_facet	Abdulmalik Alqurshi K. L. Andrew. Chan Paul G. Royall
author_sort	Abdulmalik Alqurshi
title	In-situ freeze-drying - forming amorphous solids directly within capsules: An investigation of dissolution enhancement for a poorly soluble drug
title_short	In-situ freeze-drying - forming amorphous solids directly within capsules: An investigation of dissolution enhancement for a poorly soluble drug
title_full	In-situ freeze-drying - forming amorphous solids directly within capsules: An investigation of dissolution enhancement for a poorly soluble drug
title_fullStr	In-situ freeze-drying - forming amorphous solids directly within capsules: An investigation of dissolution enhancement for a poorly soluble drug
title_full_unstemmed	In-situ freeze-drying - forming amorphous solids directly within capsules: An investigation of dissolution enhancement for a poorly soluble drug
title_sort	in-situ freeze-drying - forming amorphous solids directly within capsules: an investigation of dissolution enhancement for a poorly soluble drug
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4b04b9d75e534878a545ee15a0cbf2e0
work_keys_str_mv	AT abdulmalikalqurshi insitufreezedryingformingamorphoussolidsdirectlywithincapsulesaninvestigationofdissolutionenhancementforapoorlysolubledrug AT klandrewchan insitufreezedryingformingamorphoussolidsdirectlywithincapsulesaninvestigationofdissolutionenhancementforapoorlysolubledrug AT paulgroyall insitufreezedryingformingamorphoussolidsdirectlywithincapsulesaninvestigationofdissolutionenhancementforapoorlysolubledrug
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In-situ freeze-drying - forming amorphous solids directly within capsules: An investigation of dissolution enhancement for a poorly soluble drug

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