Double action of HPMCAS as a dry binder and precipitation inhibitor in ASD tablet formulations of nifedipine prepared by hot-melt extrusion

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 high ASD load (65 %) tablets 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 drug precipitation and prolonged its supersaturation state at 12.5 wt % or 100 wt % relative to NIF content in ASDs prepared with either HPMCAS (1: 2, drug: polymer), or PVP-VA64 (1: 6, drug: polymer), respectively. In contrast, pre-dissolving hydroxypropyl cellulose (Klucel™, HPC-EXF) or PVP-VA64, did not prevent the drug re-crystallization. The external addition of AS-HF (5 % <i>w</i>/w) to the ASD tablets of NIF: HPMCAS (1: 2) improved the tabletability, compressibility and compactibility of the blend, resulting in tablets with good tensile strength (1.9 MPa) vs 1.5 MPa or 0.8 MPa with either HPC-EXF (5 % w/w) or PVP-VA64 (5 % w/w), respectively. The results from this study demonstrate, for the first time, the dual function of HPMCAS (AS-HF) as a dry binder and precipitation inhibitor in high ASD load tablets, independent of the carrier polymer. This can potentially reduce the pill burden and improve the drug bioavailability in ASD tablet formulations.