A combined mathematical model linking the formation of amorphous solid dispersions with hot-melt-extrusion process parameters

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 132; pp. 127 - 145
• Main Authors: Schittny, A., Ogawa, H., Huwyler, J., Puchkov, M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2018
• Subjects: Amorphous solid dispersion; Bioavailability; Chemistry, Pharmaceutical - methods; Drug Compounding - methods; Drug Delivery Systems; Drug Development - methods; Formulation development; Hot Temperature; Hot-melt extrusion; Models, Theoretical; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - chemistry; Polymers - chemistry; Poorly water-soluble drugs; Process modeling; Solubility; Hot-melt extrusion; Formulation development; Amorphous solid dispersion; Poorly water-soluble drugs; Process modeling; Bioavailability
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2018.09.011

[Display omitted] Hot-melt extrusion allows for the continuous production of amorphous solid dispersions, which are used to enhance bioavailability of poorly soluble drugs in pharmaceutical drug delivery. To facilitate formulation and extrusion process development, we propose a mathematical model describing the formation of amorphous solid dispersions in the context of this process. The model is based on the calculation of two key process values: (1) time to dissolution of solid drug particles in molten polymer during extrusion and (2) mean residence of material in the extruder. We suggest that their linking allows for rational process design. Experimental data support the validity of our model for both key process values as well as the overall process. This modeling approach allows for fast and cost-effective formulation and extrusion process development as well as feasibility estimations in early stages of drug development.