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Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation

This study aims to develop amorphous solid dispersion (ASD) of lumefantrine with a cost-effective approach of spray anti-solvent precipitation. Four acidic polymers, hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), poly(methacrylic acid–ethyl a...

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Autores principales: Bhujbal, Sonal V., Pathak, Vaibhav, Zemlyanov, Dmitry Y., Taylor, Lynne S., Zhou, Qi (Tony)
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141512/
https://www.ncbi.nlm.nih.gov/pubmed/33387599
http://dx.doi.org/10.1016/j.xphs.2020.12.033
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author Bhujbal, Sonal V.
Pathak, Vaibhav
Zemlyanov, Dmitry Y.
Taylor, Lynne S.
Zhou, Qi (Tony)
author_facet Bhujbal, Sonal V.
Pathak, Vaibhav
Zemlyanov, Dmitry Y.
Taylor, Lynne S.
Zhou, Qi (Tony)
author_sort Bhujbal, Sonal V.
collection PubMed
description This study aims to develop amorphous solid dispersion (ASD) of lumefantrine with a cost-effective approach of spray anti-solvent precipitation. Four acidic polymers, hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), poly(methacrylic acid–ethyl acrylate) (EL100) and cellulose acetate phthalate (CAP) were studied as excipients at various drug-polymer ratios. Of the studied polymers, satisfactory physical stability was demonstrated for HPMCP- and HPMCAS-based ASDs with no observed powder X-ray diffraction peaks for up to 3 months of storage at 40 °C/75% RH. HPMCP and HPMCAS ASDs also achieved greater drug release levels in the dissolution study than other polymers. The HPMCP-based ASDs with a drug:polymer ratio of 2:8 exhibited a maximum drug release of 140 μg/mL for up to 2 h, which is significantly higher than the currently marketed formulation of Coartem® (<80 ng/mL). Relatively, the CAP and EL100 ASDs indicated a higher water content and crystallized within a day when stored at 40 °C/75% RH. The choice of polymer, and the drug-polymer ratio played a crucial role in the solubility enhancement of lumefantrine. Our study indicates that the developed spray anti-solvent precipitation method could be an affordable approach for producing ASDs.
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spelling pubmed-81415122021-06-01 Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation Bhujbal, Sonal V. Pathak, Vaibhav Zemlyanov, Dmitry Y. Taylor, Lynne S. Zhou, Qi (Tony) J Pharm Sci Research Article This study aims to develop amorphous solid dispersion (ASD) of lumefantrine with a cost-effective approach of spray anti-solvent precipitation. Four acidic polymers, hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), poly(methacrylic acid–ethyl acrylate) (EL100) and cellulose acetate phthalate (CAP) were studied as excipients at various drug-polymer ratios. Of the studied polymers, satisfactory physical stability was demonstrated for HPMCP- and HPMCAS-based ASDs with no observed powder X-ray diffraction peaks for up to 3 months of storage at 40 °C/75% RH. HPMCP and HPMCAS ASDs also achieved greater drug release levels in the dissolution study than other polymers. The HPMCP-based ASDs with a drug:polymer ratio of 2:8 exhibited a maximum drug release of 140 μg/mL for up to 2 h, which is significantly higher than the currently marketed formulation of Coartem® (<80 ng/mL). Relatively, the CAP and EL100 ASDs indicated a higher water content and crystallized within a day when stored at 40 °C/75% RH. The choice of polymer, and the drug-polymer ratio played a crucial role in the solubility enhancement of lumefantrine. Our study indicates that the developed spray anti-solvent precipitation method could be an affordable approach for producing ASDs. Elsevier 2021-06 /pmc/articles/PMC8141512/ /pubmed/33387599 http://dx.doi.org/10.1016/j.xphs.2020.12.033 Text en © 2020 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Bhujbal, Sonal V.
Pathak, Vaibhav
Zemlyanov, Dmitry Y.
Taylor, Lynne S.
Zhou, Qi (Tony)
Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation
title Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation
title_full Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation
title_fullStr Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation
title_full_unstemmed Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation
title_short Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation
title_sort physical stability and dissolution of lumefantrine amorphous solid dispersions produced by spray anti-solvent precipitation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141512/
https://www.ncbi.nlm.nih.gov/pubmed/33387599
http://dx.doi.org/10.1016/j.xphs.2020.12.033
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