Hot-melt extrusion has been used in the plastics & food industries for decades. In the 1980s, BASF became the first company to apply it to the production of pharmaceuticals for enhancing the solubility and bioavailability of poorly soluble actives. Today, HME is an accepted process for creating solid dispersions of APIs.
Hot-melt extrusion for enhanced solubility and bioavailability
The solubility and bioavailability of poorly soluble APIs is often enhanced when they are molecularly dispersed in a polymeric carrier. This makes hot melt extrusion (HME) a valuable technology for the pharmaceutical industry – and opens new doors for formulators working with promising actives that cannot otherwise be solubilized. HME also grants manufacturers a great amount of flexibility, as the viscous fluid obtained from the extrusion process can be directly shaped into any desired form. In addition, the extrudates usually have a high density, which makes them suitable for producing controlled-release dosage forms.
Our aim is to help our customers discover the many benefits of this technology, and assist them in leveraging it for their products. The true potential of hot-melt extrusion for pharmaceutical applications is just beginning to be uncovered – and our research continues to blaze new trails in this exciting field.
The hot-melt extrusion process at a glance
In the pharmaceutical industry, hot-melt extrusion is used to prepare solid dispersions of poorly soluble active pharmaceutical ingredients, and for creating controlled-release medications. In this process, active ingredients are compounded with polymers that have suitable glass transition temperatures (such as Soluplus®), and extruded at an appropriate temperature to form a solid dispersion. This polymer matrix acts as a solid solvent for the drug molecules. The API can be amorphous, molecularly dispersed or crystalline dispersed within the polymer – depending on the application. The extrudate is suitable for direct shaping, granules, spheres, powders, films, patches, and injections.
Using hot-melt extrusion to produce solid dispersions
To transform an API into its amorphous form, it is necessary to overcome its crystal lattice energy. Afterwards, the API is blended with a polymer and co-dispersed. Both steps take place in an extruder. First, the crystalline API and the amorphous polymer are fed into the extruder, before being conveyed and exposed to shear stress. The resulting dispersion (referred to as extrudate) is then pressed out and collected for further processing. For more information, please see the second edition of our Hot-Melt Extrusion Compendium.
BASF functional excipients for hot-melt extrusion
To prepare a solid dispersion, the active ingredient must be embedded in a matrix. If the matrix cannot sufficiently solubilize the active ingredient solubilizers must be added. Soluplus exhibits both matrix-forming and solubilization properties – making it ideal for such cases. If the extrusion process temperature is below 100° C, a plasticizer may also be necessary. This is particularly important in cases where the active ingredient is processed without melting, i.e. where it cannot act as a plasticizing agent.
Dissolution enhancers are the fourth component of solid dispersions. They are usually added because low-porosity solid dispersions prepared via HME typically have limited disintegration capability.
Hot melt extrusion & solubilizer compendia by BASF