Binary Amorphous Solid Dispersions Research Articles

Mechanochemical Approach to Obtaining a Multicomponent Fisetin Delivery System Improving Its Solubility and Biological Activity.

In this study, binary amorphous solid dispersions (ASDs, fisetin-Eudragit®) and ternary amorphous solid inclusions (ASIs, fisetin-Eudragit®-HP-β-cyclodextrin) of fisetin (FIS) were prepared by the mechanochemical method without solvent. The amorphous nature of FIS in ASDs and ASIs was confirmed using XRPD (X-ray powder diffraction). DSC (Differential scanning calorimetry) confirmed full miscibility of multicomponent delivery systems. FT-IR (Fourier-transform infrared analysis) confirmed interactions that stabilize FIS's amorphous state and identified the functional groups involved. The study culminated in evaluating the impact of amorphization on water solubility and conducting in vitro antioxidant assays: 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)-ABTS, 2,2-diphenyl-1-picrylhydrazyl-DPPH, Cupric Reducing Antioxidant Capacity-CUPRAC, and Ferric Reducing Antioxidant Power-FRAP and in vitro neuroprotective assays: inhibition of acetylcholinesterase-AChE and butyrylcholinesterase-BChE. In addition, molecular docking allowed for the determination of possible bonds and interactions between FIS and the mentioned above enzymes. The best preparation turned out to be ASI_30_EPO (ASD fisetin-Eudragit® containing 30% FIS in combination with HP-β-cyclodextrin), which showed an improvement in apparent solubility (126.5 ± 0.1 µg∙mL-1) and antioxidant properties (ABTS: IC50 = 10.25 µg∙mL-1, DPPH: IC50 = 27.69 µg∙mL-1, CUPRAC: IC0.5 = 9.52 µg∙mL-1, FRAP: IC0.5 = 8.56 µg∙mL-1) and neuroprotective properties (inhibition AChE: 39.91%, and BChE: 42.62%).

High energy ball milling vs. nano spray drying in the development of supersaturated systems loaded with bosentan

In this study, high energy ball milling and nano spray drying were used to prepare amorphous solid dispersions of bosentan in copovidone for the first time. In particular, the impact of this polymer on the bosentan amorphization kinetics was investigated. Copovidone was shown to facilitate the amorphization of bosentan upon ball milling. As a result, bosentan was dispersed in copovidone at the molecular level, forming amorphous solid dispersions, regardless of the ratio of the compounds. The similarity between the values of the adjustment parameter that describes the goodness of fit of the Gordon-Taylor equation to the experimental data (K = 1.16) and that theoretically calculated for an ideal mixture (K = 1.13) supported these findings. The kind of coprocessing method determined the powder microstructure and the release rate. The opportunity to prepare submicrometer-sized spherical particles using nano spray drying was an important advantage of this technology. Both coprocessing methods allowed the formation of long-lasting supersaturated bosentan solutions in the gastric environment with maximum concentrations reached ranging from four (11.20 μg/mL) to more than ten times higher (31.17 μg/mL) than those recorded when the drug was vitrified alone (2.76 μg/mL). Moreover, this supersaturation lasted for a period of time at least twice as long as that of the amorphous bosentan processed without copovidone (15 min vs. 30–60 min). Finally, these binary amorphous solid dispersions were XRD-amorphous for a year of storage under ambient conditions.

Enhancing solubility and bioavailability of coenzyme Q10: formulation of solid dispersions using Soluplus® as a carrier.

Improving the aqueous solubility of poorly soluble compounds have been a major issue in the pharmaceutical industry. In the present study, binary amorphous solid dispersions (SDs) of Coenzyme Q10 (CoQ10), a biopharmaceutics classification system (BCS) II compound and Soluplus® were prepared to enhance the solubility and pharmacokinetic properties compared to crystalline CoQ10. SDs were prepared with different ratios of CoQ10 and Soluplus® (1:3, 1:5, and 1:7) using spray drying technology, and the physicochemical properties of the SDs were evaluated. X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy suggested the conversion of the crystalline form of CoQ10 to a binary amorphous system in the SDs. Fourier transform infrared spectroscopy revealed no potential interactions between CoQ10 and Soluplus®. The solubility of the optimal SD formulation (SD 1:7) was approximately 9000-fold higher than that of crystalline CoQ10, and the increment was Soluplus® concentration dependent. As a result, optimized SD 1:7 also showed significantly enhanced dissolution rate where maximum drug release was observed within 30min in two different dissolution media. Moreover, in contrast to crystalline CoQ10, CoQ10 SDs showed improved pharmacokinetic parameters. Thus, the SD 1:7 formulation is expected to improve biopharmaceutical properties and therapeutic efficacy of CoQ10.