Factors That Influence Sustained Release from Hot-Melt Extrudates

Hot-melt extrusion is a well-established tool in the pharmaceutical industry, mostly implemented to increase the solubility of poorly soluble drugs. A less frequent application of this technique is to obtain formulations with extended release. This study investigated the influence of polymer choice, drug loading, milling and hydrodynamics on the release of a model drug, flurbiprofen, from sustained-release hot-melt extrudates with Eudragit polymers. The choice of polymer and degree of particle size reduction of the extrudate by milling were the two key influences on the release profile: the percentage release after 12 h varied from 6% (2 mm threads) to 84% (particle size <125 & mu;m) for Eudragit RL extrudates vs. 4.5 to 62% for the corresponding Eudragit RS extrudates. By contrast, the release profile was largely independent of drug loading and robust to hydrodynamics in the dissolution vessel. Thus, hot-melt extrusion offers the ability to tailor the release of the API to the therapeutic indication through a combination of particle size and polymer choice while providing robustness over a wide range of hydrodynamic conditions.

Automated summary

Hot-melt extrusion is widely used in the pharmaceutical industry to increase the solubility of poorly soluble drugs. This study investigated the release of flurbiprofen from sustained-release hot-melt extrudates with different Eudragit polymers. The choice of polymer and particle size reduction by milling were found to be key factors influencing the release profile, while drug loading and hydrodynamics had minimal impact. Hot-melt extrusion allows for tailored drug release through particle size and polymer selection, with robustness under various hydrodynamic conditions.