Enhanced Bioavailability of AC1497, a Novel Anticancer Drug Candidate, via a Self-Nanoemulsifying Drug Delivery System

Abstract

AC1497 is an effective dual inhibitor of malate dehydrogenase 1 and 2 targeting cancer metabolism. However, its poor aqueous solubility results in low bioavailability, limiting its clinical development. This study was conducted to develop an effective self-nanoemulsifying drug delivery system (SNEDDS) of AC1497 to improve its oral absorption. Based on the solubility of AC1497 in various oils, surfactants, and cosurfactants, Capryol 90, Kolliphor RH40, and Transcutol HP were selected as the components of SNEDDS. After testing various weight ratios of Capryol 90 (20–30%), Kolliphor RH40 (35–70%), and Transcutol HP (10–35%), SNEDDS-F4 containing 20% Capryol 90, 45% Kolliphor RH40, and 35% Transcutol HP was identified as an optimal SNEDDS with a narrow size distribution (17.8 ± 0.36 nm) and high encapsulation efficiency (93.6 ± 2.28%). Drug release from SNEDDS-F4 was rapid, with approximately 80% of AC1497 release in 10 min while the dissolution of the drug powder was minimal (<2%). Furthermore, SNEDDS-F4 significantly improved the oral absorption of AC1497 in rats. The maximum plasma concentration and area under the plasma concentration–time curve of AC1497 were, respectively 6.82- and 3.14-fold higher for SNEDDS-F4 than for the drug powder. In conclusion, SNEDDS-F4 with Capryol 90, Kolliphor RH40, and Transcutol HP (20:45:35, w/w) effectively improves the solubility and oral absorption of AC1497.

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization

“…Depending on the inherent solubility and permeability of drug molecules, researchers have explored various formulation approaches for improvement [ 10 ]. Based on the methods reported in the literature, lipid-based drug delivery, micronization, use of polymorphs, co-crystals, salt formation, prodrug, nanocrystal dispersion, cyclodextrin complexation, binding to ion exchange resins, and amorphization were found to be effective [ 11 , 12 , 13 , 14 ]. Among these solubility enhancement technologies, amorphous solid dispersions (ASDs) have attracted tremendous importance in the last decade with numerous marketed products.…”

Formulation development, optimization and characterization of Pemigatinib-loaded supersaturable self-nanoemulsifying drug delivery systems

“…Both the formulations were evaluated for dilution and pH stability by diluting the samples 1000 folds in glass vials with distilled water, phosphate buffer (pH 6.8) and acid buffer (pH 1.2). The diluted samples were observed for any sort of instability after 24 h [28].…”

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“…3A and 3B; the contour and surface plots show the transmittance which is impacted by each and every factor. The relationship can be seen by the equation below: Effect of dilution medium and robustness to dilution was observed by diluting the SNEDDS 50, 100, and 1000 times with distilled water, 0.1 N HCl buffer (pH 1.2), and phosphate buffer (pH 6.8) 31,32 .…”