Rational Design Of Oral Nanosuspensions For Insoluble Drugs

By Jim Huang, PhD, Founder & CEO, Ascendia Pharmaceuticals

A pharmaceutical nanosuspension is a fine dispersion of nanosized, insoluble API solid particles in a liquid medium. The particle diameter in a nanosuspension is usually less than 0.5 μm. Nanosuspensions are an important class of pharmaceutical dosage forms, particularly for pharmaceutical compounds with solubility and bioavailability challenges. Nanosizing is a widely used formulation method for sparingly soluble compounds as nanosuspensions offer an attractive option to enhance the rate of dissolution and solubility of poorly soluble drugs replaced by those compounds. The saturation solubility of the nanocrystals is highly related to the particle size, and solubility increases with particle size decrease due to the increased surface area, especially when the nanocrystals are below 300 nm. Consequently, the concentration gradient between gut lumen and blood is increased, resulting in improved absorption by passive diffusion. In these nanosuspension formulations, the rate-limiting step for drug absorption is normally the insoluble drug particle dissolution in the fluid surrounding the drug formulation.

The advantages of nanosuspension dosage forms include improving bioavailability, eliminating food effect, increasing drug loading, eliminating cosolvents, masking of bad API taste, improving API stability, dose reduction, better dose flexibility and accuracy, and easy swallowing for pediatric or geriatric populations.