Nano-formulation of poorly water-soluble drugs has brou
ght two proven benefits to commercial drug products. One is it enhances drug dissolution and oral bioavailability. Second, nano-formulation increases drug loading and release duration for parenteral drug delivery. In the June issue of Drug Development & Delivery, Ascendia Pharmaceutical Solutions CEO Jim Huang, Ph.D., discusses one method of preparing nanosuspensions – the top-down process – in his Formulation Forum column.
In the column, Dr. Huang focuses on the importance optimizing the top-down process – aka wet milling. By doing so, drug development teams and their CDMO partners can better determine the critical process parameters with the aid of factorial design during scale up. He also discusses successful nanosuspension formulation development.
A main consideration mentioned in the article is the careful evaluation of compound physical chemical and biopharmaceutical properties, such as solubility, pKa, solid surface properties, permeability, melting point, and crystal lattice structure. Dr. Huang also outlines that a good candidate for nanosuspension has the characteristics of BCS Class II compounds, such as low solubility, high melting point, high permeability, and a strong tendency of food effects.
Vital Formulation and Process Factors
Other important formulation and process variables are discussed, as well. These include stabilizer concentration, drug loading, milling speed, milling time, bead diameter/density, temperature, and the amount of beads versus drug product. Drug development teams at pharmaceutical and biopharma companies can follow the recommendations in the Formulation Forum to help establish a robust formulation and manufacturing process.
If you’d like to learn more about nano-formulation of poorly water-soluble drugs, contact us. We can discuss how we can help make the insoluble soluble.