Role of phospholipids on drug dissolution in polymer solid dispersions prepared by hot-melt extrusion

Abstract

The development of solid dispersions (SDs) has gained increased attention in recent decades, leading to successful delivery systems for various marketed products. In general, combinations of polymers and lipids in SD formulations have shown promising results in reducing the disadvantages associated with the isolated use of hydrophilic excipients such as copovidone (COP) and Soluplus (SLP). This study investigated the influence of the phospholipid (soy phosphatidylcholine, PPC, 15 and 30%, w/w) on the dissolution performance of drug-polymer SDs prepared by hot melt extrusion. A low-solubility model drug (ritonavir, RTV) was selected for the study. A complete drug amorphization was observed for all extrudates despite the PPC presence. However, PPC improved the process yield without requiring a plasticizer. Morphology and particle size analyses revealed the effects of PPC addition in the aqueous dispersions prepared from SDs, denoting a higher polymer–lipid interaction in COP dispersions and the formation of micrometric structures in both COP and SLP dispersions. COP-based SDs produced almost instantaneous increases in RTV dissolution of up to 7-fold, while SLP-based SDs achieved progressive increases over 5-fold. Importantly, PPC incorporation in COP-based SDs did not have an apparent effect on RTV dissolution but significantly improved drug dissolution from the SLP-based SDs. In summary, the role of the lipid mainly depends on the drug-polymer interactions and lipid concentration. Adding phospholipids enables the thermal process without needing other adjuvants.