Self‐Emulsifying Drug Delivery of Khellin for Improving Its Oral Bioavailability

Abstract

AbstractSelf‐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.