Next Article in Journal
Montelukast Nanocrystals for Transdermal Delivery with Improved Chemical Stability
Previous Article in Journal
MRI/Photoluminescence Dual-Modal Imaging Magnetic PLGA Nanocapsules for Theranostics
Previous Article in Special Issue
Ionic Liquids as Potential and Synergistic Permeation Enhancers for Transdermal Drug Delivery
Open AccessArticle

Ionic Liquid Forms of the Antimalarial Lumefantrine in Combination with LFCS Type IIIB Lipid-Based Formulations Preferentially Increase Lipid Solubility, In Vitro Solubilization Behavior and In Vivo Exposure

1
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia
2
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia
3
Oral Drug Delivery Innovation, Lonza Pharma Biotech & Nutrition, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia
4
Oral Drug Delivery Innovation, Lonza Pharma Biotech & Nutrition, 67412 Strasbourg, France
5
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(1), 17; https://doi.org/10.3390/pharmaceutics12010017
Received: 28 November 2019 / Revised: 15 December 2019 / Accepted: 18 December 2019 / Published: 22 December 2019
Lipid based formulations (LBFs) are commonly employed to enhance the absorption of highly lipophilic, poorly water-soluble drugs. However, the utility of LBFs can be limited by low drug solubility in the formulation. Isolation of ionizable drugs as low melting, lipophilic salts or ionic liquids (ILs) provides one means to enhance drug solubility in LBFs. However, whether different ILs benefit from formulation in different LBFs is largely unknown. In the current studies, lumefantrine was isolated as a number of different lipophilic salt/ionic liquid forms and performance was assessed after formulation in a range of LBFs. The solubility of lumefantrine in LBF was enhanced 2- to 80-fold by isolation as the lumefantrine docusate IL when compared to lumefantrine free base. The increase in drug loading subsequently enhanced concentrations in the aqueous phase of model intestinal fluids during in vitro dispersion and digestion testing of the LBF. To assess in vivo performance, the systemic exposure of lumefantrine docusate after administration in Type II-MCF, IIIB-MCF, IIIB-LCF, and IV formulations was evaluated after oral administration to rats. In vivo exposure was compared to control lipid and aqueous suspension formulations of lumefantrine free base. Lumefantrine docusate in the Type IIIB-LCF showed significantly higher plasma exposure compared to all other formulations (up to 35-fold higher). The data suggest that isolation of a lipid-soluble IL, coupled with an appropriate formulation, is a viable means to increase drug dose in an oral formulation and to enhance exposure of lumefantrine in vivo. View Full-Text
Keywords: ionic liquid; lipophilic salt; drug delivery; drug absorption; poorly water-soluble drug; lumefantrine; lipid-based formulation; SEDDS; lipid formulation classification system ionic liquid; lipophilic salt; drug delivery; drug absorption; poorly water-soluble drug; lumefantrine; lipid-based formulation; SEDDS; lipid formulation classification system
Show Figures

Graphical abstract

MDPI and ACS Style

Tay, E.; Nguyen, T.-H.; Ford, L.; Williams, H.D.; Benameur, H.; Scammells, P.J.; Porter, C.J.H. Ionic Liquid Forms of the Antimalarial Lumefantrine in Combination with LFCS Type IIIB Lipid-Based Formulations Preferentially Increase Lipid Solubility, In Vitro Solubilization Behavior and In Vivo Exposure. Pharmaceutics 2020, 12, 17.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop