Self-Emulsifying Drug Delivery of Khellin for Improving Its Oral Bioavailability
Self-emulsifying drug delivery system (SEDDS) is extensively used for enhancing the solubility, dissolution, and pharmacokinetics of poorly soluble drugs. Khellin is a natural product with multiple pharmacological activities and has inspired the discovery of two first-in-class drugs, amiodarone hydrochloride and sodium cromoglycate. The poor-aqueous solubility is one of the limitations in developing this molecule. Herein, we aimed to improve the drug loading of khellin by developing its SEDDS formulation. A combination of castor oil, tetraethylene glycol, and Transcutol HP (10 : 30 : 60 v/v) was identified, inhibiting the drug‘s precipitation post-dilution in an aqueous media. The optimized formulation, SB-16KD, was characterized using 1H NMR, DSC, and FTIR to understand khellin‘s physical/chemical interaction with the formulation excipients. The in vitro dissolution studies of khellin in SB-16KD correlated well with the oral pharmacokinetics in Wistar rats (1.6 vs. 1.7-fold). The comparative oral pharmacokinetics of formulation against native khellin was performed at 45 mg/kg in Wistar rats. The results were promising, with 1.7-fold higher plasma exposure by SEDDS formulation. Hence, the results warrant further developmental studies on SEDDS in dose reduction.
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, , , , Self-Emulsifying Drug Delivery of Khellin for Improving Its Oral Bioavailability, ChemistrySelect 2023, 8,
https://doi.org/10.1002/slct.202302620