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Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation.
J Pharm Sci. 2021 06; 110(6):2423-2431.JP

Abstract

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.

Authors+Show Affiliations

Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.Birck Nanotechnology Center, Purdue University, 1205 West State Street, West Lafayette, IN 47907, USA.Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA. Electronic address: lstaylor@purdue.edu.Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA. Electronic address: tonyzhou@purdue.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33387599

Citation

Bhujbal, Sonal V., et al. "Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced By Spray Anti-Solvent Precipitation." Journal of Pharmaceutical Sciences, vol. 110, no. 6, 2021, pp. 2423-2431.
Bhujbal SV, Pathak V, Zemlyanov DY, et al. Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation. J Pharm Sci. 2021;110(6):2423-2431.
Bhujbal, S. V., Pathak, V., Zemlyanov, D. Y., Taylor, L. S., & Zhou, Q. T. (2021). Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation. Journal of Pharmaceutical Sciences, 110(6), 2423-2431. https://doi.org/10.1016/j.xphs.2020.12.033
Bhujbal SV, et al. Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced By Spray Anti-Solvent Precipitation. J Pharm Sci. 2021;110(6):2423-2431. PubMed PMID: 33387599.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation. AU - Bhujbal,Sonal V, AU - Pathak,Vaibhav, AU - Zemlyanov,Dmitry Y, AU - Taylor,Lynne S, AU - Zhou,Qi Tony, Y1 - 2020/12/31/ PY - 2020/07/27/received PY - 2020/11/12/revised PY - 2020/12/14/accepted PY - 2021/1/3/pubmed PY - 2021/1/3/medline PY - 2021/1/2/entrez KW - Amorphous solid dispersion KW - Dissolution KW - Moisture sorption KW - Physical stability KW - Precipitation SP - 2423 EP - 2431 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 110 IS - 6 N2 - 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. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/33387599/Physical_Stability_and_Dissolution_of_Lumefantrine_Amorphous_Solid_Dispersions_Produced_by_Spray_Anti_Solvent_Precipitation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(20)30846-7 DB - PRIME DP - Unbound Medicine ER -