Hot Melt Extrusion at Sever Pharma Solutions

HOT MELT EXTRUSION AND SOLUBILIZATION
Approximately 90% of active pharmaceutical ingredients (APIs) in development are estimated to be poorly water-soluble (PWS)1. Hot Melt Extrusion (HME) is one of several solubilization techniques used by the pharmaceutical industry to enhance the solubility of APIs. HME is a desirable strategy because it is a controllable process that promotes miscibility of the API in a polymer matrix, it is a continuous manufacturing process that takes up a relatively small footprint, and it is solvent-free and scale-able.
Class I - High Permeability, High Solubility
Class II - High Permeability, Low Solubility
Class III - Low Permeability, High Solubility
Class IV - Low Permeability, Low Solubility
HME technology can be used to address BCS Class II molecules by improving the dissolution rate of PWS drugs to enhance their bioavailability after oral administration. These crystalline hydrophobic drugs are dispersed in hydrophilic polymers using HME to create amorphous solid dispersions.
APIs are commonly characterized using the Biopharmaceutics Classification System (BCS). The BCS system consists of the following four classes:
Formulation development involves the development of an API-polymer mixture that provides the desired release characteristics. Drug release is evaluated in-vitro by performing a dissolution test.
The scale of development is from mg quantities evaluated on a hot stage microscope and/or a differential scanning calorimeter (DSC). Small-scale studies can be performed using a vacuum compression molding (VCM) technique at a different time and temperature conditions. VCM studies are also conducted at the mg scale. Pre-clinical extrusion studies are typically performed at the 20-30g scale. The scale for clinical studies can be in the 100g batch size. Commercial manufacturing of GMP batches is in the 10s of kgs/hr range.