Solid-State Behavior and Solubilization of Flash Nanoprecipitated Clofazimine Particles during the Dispersion and Digestion of Milk-Based Formulations

Malinda Salim, Gisela Ramirez, Andrew J. Clulow, Yingyue Zhang, Kurt D. Ristroph, Jie Feng, Simon A. McManus, Adrian Hawley, Robert K. Prud'Homme, Ben J. Boyd

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Clofazimine, a drug previously used to treat leprosy, has recently been identified as a potential new drug for the treatment for cryptosporidiosis: a diarrheal disease that contributes to 500 000 infant deaths a year in developing countries. Rapid dissolution and local availability of the drug in the small intestine is considered key to the treatment of the infection. However, the commercially available clofazimine formulation (Lamprene) is not well-suited to pediatric use, and therefore reformulation of clofazimine is desirable. Development of clofazimine nanoparticles through the process of flash nanoprecipitation (FNP) has been previously shown to provide fast and improved drug dissolution rates compared to clofazimine crystals and Lamprene. In this study, we investigate the effects of milk-based formulations (as possible pediatric-friendly vehicles) on the in vitro solubilization of clofazimine formulated as either lecithin- or zein/casein-stabilized nanoparticles. Milk and infant formula were used as the lipid vehicles, and time-resolved synchrotron X-ray scattering was used to monitor the presence of crystalline clofazimine in suspension during in vitro lipolysis under intestinal conditions. The study confirmed faster dissolution of clofazimine from all the FNP formulations after the digestion of infant formula was initiated, and a reduced quantity of fat was required to achieve similar levels of drug solubilization compared to the reference drug material and the commercial formulation. These attributes highlight not only the potential benefits of the FNP approach to prepare drug particles but also the fact that enhanced dissolution rates can be complemented by considering the amount of co-administered fat in lipid-based formulations to drive the solubilization of poorly soluble drugs.

Original languageEnglish
Pages (from-to)2755-2765
Number of pages11
JournalMolecular Pharmaceutics
Volume16
Issue number6
DOIs
Publication statusPublished - 3 Jun 2019

Keywords

  • clofazimine
  • drug solubilization
  • in vitro digestion
  • infant formula
  • milk
  • nanoparticles
  • X-ray scattering

Cite this

Salim, Malinda ; Ramirez, Gisela ; Clulow, Andrew J. ; Zhang, Yingyue ; Ristroph, Kurt D. ; Feng, Jie ; McManus, Simon A. ; Hawley, Adrian ; Prud'Homme, Robert K. ; Boyd, Ben J. / Solid-State Behavior and Solubilization of Flash Nanoprecipitated Clofazimine Particles during the Dispersion and Digestion of Milk-Based Formulations. In: Molecular Pharmaceutics. 2019 ; Vol. 16, No. 6. pp. 2755-2765.
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Solid-State Behavior and Solubilization of Flash Nanoprecipitated Clofazimine Particles during the Dispersion and Digestion of Milk-Based Formulations. / Salim, Malinda; Ramirez, Gisela; Clulow, Andrew J.; Zhang, Yingyue; Ristroph, Kurt D.; Feng, Jie; McManus, Simon A.; Hawley, Adrian; Prud'Homme, Robert K.; Boyd, Ben J.

In: Molecular Pharmaceutics, Vol. 16, No. 6, 03.06.2019, p. 2755-2765.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Salim, Malinda

AU - Ramirez, Gisela

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AU - Zhang, Yingyue

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AU - Feng, Jie

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AU - Boyd, Ben J.

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