Melt processability of amorphous solid dispersions during hot-melt extrusion. Screening using vacuum compression moulding and evaluation by rheology and solid-state analysis

Abstract

Soluplus is a suitable excipient for innovative manufacturing techniques such as hot-melt extrusion (HME). While Soluplus is useful for forming amorphous solid dispersions (ASD’s) during HME, the resulting extrudates are often stiff and brittle. In order to achieve suitable dosage forms, with optimal downstream processability, an efficient screening for suitable formulations is required. Vacuum compression moulding (VCM) is a rapid, cost-efficient sample preparation method for thermoplastic materials that could possibly be used as a reliable screening tool. Solid dispersions with 10%, 30% and 50% w/w drug load of naproxen (NAP) or celecoxib (CCX) in Soluplus were prepared by HME and VCM under controlled conditions (HME: 120°C, 0 and 5 min recirculation, 50RPM, VCM: 120°C, 15 min). Melt processability and the effect of drug load were evaluated using rheology, subjecting the samples to a frequency sweep from 100-0.01 Hz at 120°C within the linear viscoelastic region. The samples were also analysed using differential scanning calorimetry (DSC), polarized light microscopy (PLM) and Raman Spectroscopy. The stability during storage of the solid dispersions prepared using HME was also investigated.

The complex viscosity (ƞ*) between the different preparative methods varied considerably especially at the higher drug-loads. The lack of mixing and shear forces in VCM leads to less amorphisation and higher crystal content of drug in the mixture, which increases the melt viscosity. The difference is especially evident at higher drug loads where the mixing is critical for forming an ASD. The results also show that the dissolved NAP can act as a plasticizer lowering the melt viscosity of the API-polymer mixture. VCM should be used with consideration when predicting melt properties of melt extrudates, especially at higher drug loads.