Impact of hypromellose acetate succinate and Soluplus® on the performance of β-carotene solid dispersions with the aid of sorbitan monolaurate: In vitro-in vivo comparative assessment

Abstract

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.

Keywords: Hypromellose acetate succinate; Soluplus®; Ternary solid dispersions.