Abstract
Although significant actions have been taken towards the utilization of poly(vinyl alcohol) (PVA) in the preparation of drug amorphous solid dispersions (ASDs) using fusion-based techniques (such as melt-quench cooling and hot-melt extrusion), several drawbacks regarding its rather high melting temperature and its thermal degradation profile make the use of the polymer extremely challenging. This is especially important when the active pharmaceutical ingredient (API) has a lower melting temperature (than PVA) or when it is thermally labile. In this vein, a previous study showed that newly synthesized polyester-based plasticizers may improve the processability and the thermal properties of PVA. However, the effects of such polyester-based plasticizers on the drug’s physicochemical and pharmaco-technical properties are yet unknown. Hence, the aim of the present study is to extend our previous findings and evaluate the use of poly(propylene succinate) (PPSu, i.e., the most promising plasticizer in regard to PVA) in the preparation of drug-loaded PVA-based ASDs. Dronedarone (DRN), a poorly water-soluble API, was selected as a model drug, and drug ASDs (using either neat PVA or PVA-PPSu) were prepared using the melt-mixing/quench cooling approach at low melting temperatures (i.e., 170 °C). DSC and pXRD analysis showed that a portion of the API remained crystalline in the ASDs prepared only with the use of neat PVA, while the samples having PPSu as a plasticizer were completely amorphous. Further evaluation with ATR-FTIR spectroscopy revealed the formation of significant intermolecular interactions between the API and the PVA-PPSu matrix, which could explain the system’s physical stability during storage. Finally, dissolution studies, conducted under nonsink conditions, revealed that the use of PVA-PPSu is able to maintain DRN’s sustained supersaturation for up to 8 h.
Highlights
Results in this study showed that the utilization of low molecular weight (MW) poly(propylene succinate) (PPSu) was able to reduce the processing temperature of poly(vinyl alcohol) (PVA) and improve its melt flow properties without affecting its thermal decomposition
Before proceeding with the evaluation of the drug-loaded amorphous solid dispersions (ASDs), it is important to investigate the effect of the melt-mixing time on the neat polymeric PVA/PPSu matrices’ characteristics
Conclusions the intermolecular interactions formed between the active pharmaceutical ingredient (API) and the polymeric matrix during The present study showed that the use of PPSu as a plasticizer may significantly imstorage
Summary
Amongst the several preparation methods, fusion-based techniques, such as melt-quench cooling, hot-melt extrusion (HME) and KinetiSol (a fusion-based process that utilizes frictional and shear energies to rapidly transition drug–polymer blends into a molten state), are considered to be more advantageous since they are more scalable, solvent-free, continuous, fast and robust [22,23,24,25,26] Within this set framework, several excipient manufacturers have focused their product pipeline on the development of designed PVA grades suitable for the preparation of fusion-based drug ASDs, such as Merk’s Parteck
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