Double action of HPMCAS as a dry binder and precipitation inhibitor in ASD tablet formulations of nifedipine prepared by hot-melt extrusion
Year: 2025
Type: article
Abstract: Poor tablet hardness and drug re-crystallization are two common challenges of amorphous solid dispersion (ASD) formulations prepared with hot-melt extrusion (HME). In the present study, we investigated the double action of hypromellose acetate succinate (HPMCAS) as a dry binder and precipitation inhibitor when externally added to ASD tablet formulations of Nifedipine (NIF). Binary ASDs of NIF were prepared using either HPMCAS or copovidone (Kollidon® VA 64, PVP-VA64) as carrier polymers. Pre-dissolving HPMCAS (AS-HF) in the dissolution medium inhibited the precipitation of NIF and prolonged its supersaturation state at 12.5 wt% or 100 wt% relative to NIF content in ASDs prepared with HPMCAS (33 % NIF drug load), or PVP-VA64 (14.29 % NIF drug load), respectively. In contrast, pre-dissolving hydroxypropyl cellulose (Klucel™, HPC-EXF) and PVP-VA64, did not prevent the re-crystallization of NIF with both ASDs. The external addition of AS-HF (5 % w /w) to the ASD tablets of NIF/ HPMCAS improved the tabletability of the blend resulting in tablets with good tensile strength (1.9 MPa) in comparison to 1.5 MPa, or 0.8 MPa, when HPC-EXF (5 % w /w), or PVP-VA64 (5 % w/w) were added, respectively. The results from this study demonstrate, for the first time, the application of HPMCAS (AS-HF) as a dry binder in ASD tablets, in addition to its established precipitation inhibition effect.
Authors: David S. Nakhla, Saurabh M Mishra, Christian Lübbert, Luis Mejia, Kess Agatovure, Andreas Sauer
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,590
OpenAlex ID: W4417529125