Table 2.
Summary of Hot Melt Extrusion, Kinetisol®, Spray drying, and Fluidized bed Technology processes to formulate amorphous solid dispersions [49,51,88,117–127].
| Technology | Principle | Applicability | Limitations | Commercial feasibility | Commercial products | Factors affecting yield of final product |
|---|---|---|---|---|---|---|
| Hot melt extrusion | Co-dispersion of API and polymer with aid of shear stress and thermal energy | Continuous process for production of amorphous dispersions Multiple applications including solubility improvement |
Applicability to thermo liable, shear sensitive compounds and high melting point APIs | Commercially scalable, continuous and solvent free process | Kaletra®, Norvir®, Viekira XR™, Mavyret™ and Venclexta™ (AbbVie). Intelence® (Janssen), Certican and Zortress® (Novartis). | Number of mixing zones, shear, drug load, and plasticizer concentrations and type, batch size |
| Kinetisol® | Combination of collective mechanical forces leading to the increase of temperature forming a molten mixture | Specifically, applicable to drugs with high melting points and low solubility in organic solvents | Commercial scalability | Yet to be proved for continuous fullscale commercial manufacturing | No marketed amorphous solid dispersion products are available. | Processing speed, discharge temperature, lubricant levels, processing times |
| Spray drying | Formation of solid dispersion by rapid evaporation of the solvent from the fluidized drug carrier mixture leads to kinetic entrapment of drug in carrier matrix. | Encapsulation and formation of complexes in various drug delivery systems | Solvent based technique; cost effectiveness | Commercially scalable | Incivek™, Kalydeco®, Orkambi®, Symdeko and Delstrigo (Vertex) Harvoni® and Epclusa® (Gilead Sciences), Zepatier® (Merck). | Outlet and inlet temperatures, atomization gas flow rate and pressure, batch size, feed rate, total feed concentration and viscosity, carrier concentrations and grades |
| Fluidized bed Technology | Distribution of the dosage form on multiple particles which comprise a single unit | Applicability in different delivery systems and avoidance of dose dumping | High production cost Compaction problems in tablets and applicability to high doses |
Commercially scalable | Sporanox® (Janssen Pharmaceuticals), Nimotop®(Bayer) Prograf® (Astellas PharmaInc.) | Inlet air temperature, feed flow rate, atomization rate and pressure, binary nozzle air pressure and position, batch size |