Development of a sorafenib-loaded solid self-nanoemulsifying drug delivery system: Formulation optimization and characterization of enhanced properties.

Autor: Lim C; College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea., Lee D; College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea.; Department of Global Innovative Drugs, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea., Kim M; College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea.; Department of Global Innovative Drugs, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea., Lee S; College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea.; Department of Global Innovative Drugs, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea., Shin Y; College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea.; Department of Global Innovative Drugs, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea., Ramsey JD; Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599, USA., Choi HG; College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, South Korea., Lee ES; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si, Gyeonggi-do 14662, Republic of Korea., Youn YS; School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Republic of Korea., Oh KT; College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea.; Department of Global Innovative Drugs, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, South Korea.
Jazyk: angličtina
Zdroj: Journal of drug delivery science and technology [J Drug Deliv Sci Technol] 2023 Apr; Vol. 82. Date of Electronic Publication: 2023 Mar 28.
DOI: 10.1016/j.jddst.2023.104374
Abstrakt: 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.
Competing Interests: Conflict of interest The authors have no competing interests to declare. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Databáze: MEDLINE
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