Enhancing Biopharmaceutical Attributes of Khellin by Amorphous Binary Solid Dispersions.

Khellin, a furanochromone isolated from fruits and seeds of Ammi visnaga, is traditionally used in many eastern Mediterranean countries. The plant decoction and the crystalline substance khellin have many pharmacological activities. For instance, it acts as a bronchodilator and also relieves renal colic and urethral stones, etc. However, the low water solubility (~ 120 µg/mL) and low bioavailability limit its therapeutic application. Thus, the present research explores the development of its binary and ternary solid dispersion formulations to improve its solubility and dissolution behavior. A 24-well plate miniaturized protocol was established to identify the optimal hydrophilic polymer to prepare its solid dispersions. PEG-4000 was recognized as the favorable hydrophilic carrier in preparation of solid dispersion, SSB17. The formulation displayed ~ five-fold enhancement in the aqueous solubility of khellin. The binary solid dispersion SSB17 was manufactured at a gram scale and evaluated using 1H-NMR, 13C-NMR, FT-IR, p-XRD, SEM, DSC, in vitro dissolution, and predicted pharmacokinetics. The quantitative dissolution data of SSB17 demonstrated ~ 2-3-fold improvement in AUC at physiological pH conditions. These conclusions highlight the basis for further preclinical studies on solid dispersions of khellin with improved biopharmaceutical properties.