Preparation of Apixaban Solid Dispersion for the Enhancement of Apixaban Solubility and Permeability

Abstract

(1) Background: Solid dispersion (SD) can help increase the bioavailability of poorly water-soluble drugs. Meanwhile, apixaban (APX)—a new anticoagulation drug—has low water solubility (0.028 mg/mL) and low intestinal permeability (0.9 × 10−6 cm/s across Caco-2 colonic cells), thus resulting in a low oral bioavailability of <50%; (2) Methods: To solve the drawbacks of conventional APX products, a novel SD of APX in Soluplus® was prepared, characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR) spectroscopy techniques and evaluated for its solubility, intestinal permeability and pharmacokinetic performance. (3) Results: The crystallinity of the prepared APX SD was confirmed. The saturation solubility and apparent permeability coefficient increased 5.9 and 2.54 times compared to that of raw APX, respectively. After oral administration to the rats, the bioavailability of APX SD was improved by 2.31-fold compared to that of APX suspension (4) Conclusions: The present study introduced a new APX SD that potentially exhibits better solubility and permeability, thus increasing APX’s bioavailability.

Oral Drug Delivery via Intestinal Lymphatic Transport Utilizing Lipid-Based Lyotropic Liquid Crystals

“…Caco-2 cell permeability assay has been established to measure the rate of flux of a drug across polarized human colon epithelial cell lines (monolayers) [ 50 ]. The Ussing chamber system has been used to measure intestinal permeability and the transport of drugs across the epithelial tissues [ 70 ]. Tissues from the ileum were isolated after the oral administration of bile-acid-conjugated solid nanoparticles and observed with confocal microscopy to visualize the enterocytes.…”