Preserving high surface area of drug nanoparticles in nanocomposite particulates and oral stripfilms

R.N. Dave
New Jersey Institute of Technology,
United States

Keywords: nanoparticles, drug delivery

Summary:

It is estimated that majority of emerging pharmaceutical drug compounds exhibit poor water solubility. Several methods have been developed to improve the solubility and/or dissolution rate of poorly water-soluble drugs. Such methods include reduction of drug particle size, manipulation of solid state, solubilization in surfactant systems, and formation of water-soluble complexes. Each approach has certain merits and limitations. Amongst those, creation of amorphous forms and particle size reduction in particular are popular approaches for bioavailability enhancement of poorly water-soluble drugs. The latter process leads to an increase in the specific surface area of the drug particles, which, in turn, improves their dissolution rate. Among the methods used for particle size reduction, wet media milling has received much attention because of its effectiveness in producing nanoparticles of reliable and reproducible size. Notwithstanding the problems in achieving and maintaining nano sizes in suspensions, a major challenge is to retain the large surface area created after drying. Drying is accomplished through spray drying (SD), freeze drying, or granulation/coating in fluidized bed (FB) to convert nanosuspensions into nanocomposite microparticles and finally into various solid dosage forms. However, any form of drying of the nanosuspensions generally causes the nanoparticles to aggregate due to liquid removal leading to loss of the large surface area of nanoparticles. This negates any dissolution rate enhancements that may be expected due to their large surface area. Our group has focused on both the nanosuspensions stabilization and then preserving of large surface area upon drying through judicious use of stabilizers to produce final drug nanocomposites via SD, FB coating, and casting and drying of forming thin polymeric films. In this talk, we show the details of stabilization with or without use of surfactants and how large surface area may be preserved leading to very fast dissolution rates from dry nanocomposites.