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

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.

SUBMITTER: Bhujbal SV

PROVIDER: S-EPMC8141512 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Bhujbal Sonal V SV Pathak Vaibhav V Zemlyanov Dmitry Y DY Taylor Lynne S LS Zhou Qi Tony QT

Journal of pharmaceutical sciences 20201231 6

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- a ...[more]

PMID: 33387599

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Project description:Spray drying is widely used in the manufacturing of amorphous solid dispersion (ASD) systems due to its fast drying rate, enabling kinetic trapping of the drug in amorphous form. Spray-drying conditions, such as solvent composition, can have a profound impact on the properties of spray-dried dispersions. In this study, the phase behavior of spray-dried dispersions from methanol and methanol-water mixtures was assessed using ritonavir and copovidone [poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA)] as dispersion components. The resultant ASDs were characterized using differential scanning calorimetry (DSC), fluorescence spectroscopy, X-ray photoelectron spectroscopy (XPS), as well as surface-normalized dissolution rate (SNDR) measurements. Quaternary phase diagrams were calculated using a four-component Flory-Huggins model. It was found that the addition of water to the solvent system can lead to phase separation during the spray-drying process. A 10:90 H2O/MeOH solvent system caused a minor extent of phase separation. Phase heterogeneity in the 50 and 75% drug loading ASDs prepared from this spray solvent can be detected using DSC but not with other techniques used. The 25% drug loading system did not show phase heterogeneity in solid-state characterization but exhibited a compromised dissolution rate compared to that of the miscible ASD prepared from H2O-free solvent. This is possibly due to the formation of slow-releasing drug-rich phases upon phase separation. ASDs prepared with a 60:40 H2O/MeOH solvent mixture showed phase heterogeneity with all analytical methods used. The surface composition of dispersion particles as measured by fluorescence spectroscopy and XPS showed good agreement, suggesting surface drug enrichment of the spray-dried ASD particles prepared from this solvent system. Calculated phase diagrams and drying trajectories were consistent with experimental observations, suggesting that small variations in solvent composition may cause significant changes in ASD phase behavior during drying. These findings should aid in spray-drying process development for ASD manufacturing and can be applied broadly to assess the risk of phase separation for spray-drying systems using mixed organic solvents or other solvent-based processes.

Dataset Information

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

Publications

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

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