Operational Advantages Of Using Hot Melt Extrusion To Create Amorphous Solid Dispersions

Oral dosing is the most convenient method of drug delivery, typically correlating with high patient compliance. Yet the limited solubility of many modern drugs frequently translates to low bioavailability, making improved solubility a primary goal of oral dosage formulation development. To rationalize this process, drugs can be categorized into four classes based on solubility and permeability using the biopharmaceutical classification system (BCS). BCS Class II and Class IV drug molecules are defined by low aqueous solubility, a characteristic that can be combated through preparation of an amorphous solid dispersion (ASD). By locking the effective molecule in an amorphous state, ASDs improve bioavailability to provide acceptable in vivo performance. However, since amorphous states are at a higher energy level than in crystal form, and therefore less stable, ASD production requires an enabling technology. Spray drying and hot melt extrusion (HME) are among the most widely applied technologies for producing ASDs, with the latter used successfully to manufacture a wide range of drugs including AbbVie commercial products Kaletra®, Norvir®, Viekira Pak®, Mavyret® and Venclexta.