Development of a sorafenib-loaded solid self-nanoemulsifying drug delivery system: Formulation optimization and characterization of enhanced properties
Sorafenib, marketed under the brand name Nexavar®, is a multiple tyrosine kinase inhibitor drug that has been actively used in the clinical setting for the treatment of several cancers. However, the low solubility and bioavailability of sorafenib constitute a significant barrier to achieving a good therapeutic outcome. We developed a sorafenib-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation composed of capmul MCM, tween 80, and tetraglycol, and demonstrated that the SNEDDS formulation could improve drug solubility with excellent self-emulsification ability. Moreover, the sorafenib-loaded SNEDDS exhibited anticancer activity against Hep3B and KB cells, which are the most commonly used hepatocellular carcinoma and oral cancer cell lines, respectively. Subsequently, to improve the storage stability and to increase the possibility of commercialization, a solid SNEDDS for sorafenib was further developed through the spray drying method using Aerosil® 200 and PVP K 30. X-ray diffraction and differential scanning calorimeter data showed that the crystallinity of the drug was markedly reduced, and the dissolution rate of the drug was further improved in formulation in simulated gastric and intestinal fluid conditions. In vivo study, the bioavailability of the orally administered formulation increases dramatically compared to the free drug. Our results highlight the use of the solid-SNEDDS formulation to enhance sorafenib’s bioavailability and outlines potential translational directions for oral drug development.
Excipients used in the study besides other: Labrafil M 1944 CS, Labrafil M 2125, Labrasol, Transcutol P, Lauroglycol 90, Capryol 90, and Labrafac Lipophile WL 1349, Tween 80, Capmul MCM, Aerosil 200
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Chaemin Lim, Dayoon Lee, Mikyung Kim, Subin Lee, Yuseon Shin, Jacob D. Ramsey, Han-Gon Choi, Eun Seong Lee, Yu Seok Youn, Kyung Taek Oh, Development of a sorafenib-loaded solid self-nanoemulsifying drug delivery system: Formulation optimization and characterization of enhanced properties, Journal of Drug Delivery Science and Technology, Volume 82, 2023, 104374, ISSN 1773-2247,
https://doi.org/10.1016/j.jddst.2023.104374.