Enhanced felodipine dissolution from high drug loading amorphous solid dispersions with PVP/VA and sodium dodecyl sulfate

Abstract

The objective of this study was to investigate the mechanisms of sodium dodecyl sulfate (SDS) and Copovidone (PVP/VA) enhancing the dissolution of high loaded felodipine (FLDP) amorphous extrudates. The rheological results indicated that PVP/VA inhibited FLDP crystallization and the binary FLDP-PVP/VA (1:1 and 1:3) and ternary FLDP-PVP/VA-SDS (1:1:0.02–0.16 and 1:3:0.02–0.32) extrudates were amorphous solid dispersions (ASDs). Internal SDS (5%–20%) decreased glass transition temperature (Tgs) of FLDP-PVP/VA ternary ASDs. The enhanced dissolution rate of binary or ternary PVP/VA-rich ASDs in the non-sink condition of 0.05%SDS was achieved. SDS enhanced the dissolution of PVP/VA-rich ASDs via wettability and complexation with PVP/VA to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. Interestingly, when the ratio of FLDP-SDS was 1:0.08–0.12, the addition of SDS can significantly promote drug dissolution. To confirm the in vitro relevance of these molecular interaction mechanisms, we prepared two tablet formulations which internal or external added SDS, respectively, the ratio of FLDP-SDS was 1:0.1. The results show that SDS can promote the dissolution of FLDP when only SDS was internal added.