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Esaxerenone is a new nonsteroidal mineralocorticoid receptor antagonist utilized to treat high blood pressure. Chemically, esaxerenone is a pyrrole derivative consisting of hindered rotation, which results in stereoisomers named atropisomers. Currently, no methods exist for the separation and quantification of these atropisomers. A new and accurate chiral liquid chromatographic technique was developed and validated to estimate the enantiomeric purity of esaxerenone. Polar organic chiral separation was carried out on an immobilized amylose-based chiral stationary phase (Chiralpak IG) with methanol:acetonitrile:diethylamine (9:1:0.1, v/v/v) mixture as a mobile phase. The total runtime was 15 min, and the resolution (Rs) between the atropisomers was more than 3.0. The detection and quantification thresholds for the R-atropisomer were found to be 0.03 and 0.1 µg mL−1, respectively, for a test concentration of esaxerenone (1000 µg mL−1). Over the range from the limit of quantification to 0.3 percent, the method's linearity for the R-atropisomer was excellent (R2 > 0.999). The R-atropisomer recovery varied from 95 to 102%, confirming the method's good accuracy. For a 48-h research period, the chemical was shown to be stable. [ABSTRACT FROM AUTHOR]

The low oral bioavailability, short biological half-life, high dose, and frequent dosing of berberine (BBR) contribute to its restricted clinical use despite its extensive pharmacological activity. Thus, the objective of this study was to formulate sustained-release microparticles (MPs) using a pH-independent release polymer and to evaluate their potential to improve the oral bioavailability of BBR. BBR loaded MPs were prepared using the emulsion crosslinking method and evaluated for particle size, circularity, morphology, entrapment efficiency, solid-state analysis, swelling index, and in vitro BBR release study fitted with different models of release kinetics. The MPs exhibited desired particle sizes ranges between 11.09–11.62 μm and were almost spherical in shape, as confirmed by the circularity value and micrographic images. A loss of BBR crystallinity was observed after encapsulation in MPs, as evident from various solid-state analyses. The final optimized batch (F3) showed highest % BBR entrapment efficiency value of 81.63% ± 4.9. The in vitro BBR release performance in both acidic and alkaline media showed the desired sustained release behavior from the crosslinked MPs, where the maximum BBR release was observed at alkaline pH, which is in accordance with the swelling study data. In the in vivo study, the oral absorption profiles of BBR from both pristine and MPs formats were investigated using in-house prototyped 3D printed hollow capsules as a unit dose carrier. In vivo data showed sustained and prolonged absorption behavior of BBR from MPs compared to their pristine counterparts, which resulted in a cumulative increment of relative oral bioavailability to mitigate the aforementioned issues related to BBR. [ABSTRACT FROM AUTHOR]

Many diseases such as cancer are cured by natural substances, yet practical applications are limited by low pharmacodynamics due to poor solubility and permeability, photosensitivity, chemical instability, and first-pass metabolism. These issues are partly solved by nanotechnology. Here, we review briefly lipid-based nanomaterials for drug delivery. Indeed, lipid nanoconstructs allow active and passive targeting, biocompatibility, improved safety, and efficacy. Lipid nanoconstructs include both vesicular- and particulate-based systems such as liposomes, lipid micelles, solid lipid nanoparticles, and nanostructured lipid carriers. [ABSTRACT FROM AUTHOR]