Solid dispersions (SDs) possess the potential to enhance the bioavailability of insoluble active pharmaceutical ingredients (APIs) by effectively converting them into amorphous state. However, SDs have a tendency to recrystallize unless appropriate excipients are employed. The objective of this study was to evaluate the ability of hypromellose acetate succinate HF (HPMCAS-HF) and Soluplus® to inhibit the recrystallization of β-carotene and improve its in vivo bioavailability through the fabrication of ternary β-carotene solid dispersions (SDs) with the aid of specific surfactant. Due to rapid micellization , the dissolution profiles of β-carotene SDs based on HPMCAS-HF/Span 20 (5:5, w/w) or Soluplus®/Span 20 (6:4, w/w) combinations exhibited significant improvement, which were almost 7–10 times higher than β-carotene bulk powder. DSC and PXRD analysis indicated a notable reduction in the crystallinity degree of β-carotene within the SDs. The stability study demonstrated a half-life of β-carotene in the SDs exceeding 30 days. Additionally, the in vivo pharmacokinetics analysis confirmed that the cellulose derivatives/surfactant combinations significantly enhanced the bioavailability of β-carotene by 1.37-fold and 2.3-fold, respectively. Notably, the HPMCAS-HF/Span 20 combination exhibited superior performance. Consequently, the HPMCAS-HF/Span 20 combination held potential for the advancement of an effective drug delivery system for β-carotene.
In this study, the interaction among multifunctional excipients, including polysaccharides, cellulose derivatives, and surfactants, was particularly investigated, together with its impact on the physicochemical properties of astaxanthin amorphous solid dispersions (ASTX ASDs). It was indicated that Span 20 could rapidly form hemimicelles or aggregates in the presence of hypromellose acetate succinate HF (HPMCAS-HF, HF) or Soluplus®, while octenyl succinic anhydride modified starch (OSA-starch) efficiently assisted in the coalescence inhibition of drug-excipients aggregates, which was jointly beneficial to the recrystallization inhibition of amorphous ASTX. ASTX ASDs were further prepared with OSA-starch, HPMCAS-HF/Soluplus®, and Span 20 as the wall materials. DSC, SEM, and XRD confirmed that crystalline ASTX had transformed to amorphous state in the ASDs, while FT-IR spectra provided evidence suggesting the existence of hydrogen bonds and hydrophobic interaction between ASTX and the excipients. The dissolution of ASTX ASDs in different media revealed significant promotion, while the pharmacokinetic results further demonstrated the oral bioavailability of ASTX ASDs enhanced remarkably, exhibiting 2.75-fold (SD 1 ) and 1.87-fold (SD 2 ) increase, respectively, compared to ASTX bulk powder. In summary, the cellulose derivatives-surfactant interaction had great impact on the physicochemical properties of ASTX ASDs, and their combinations exhibited great potential for delivering the hydrophobic bioactive compounds efficiently.
危险品化学品经营许可证（带存储）