Nanoparticle engineering for enhanced drug delivery

Low water solubility of drug compounds limits their dissolution in the aqueous body fluids. When formulated using conventional methods, those poorly water-soluble drugs often results in low and erratic bioavailability. The use of nanoparticle engineering technologies for the formulation of poorly water-soluble drugs is a valuable strategy to enhance dissolution rates and thus bioavailability. In Chapter 2, a nanoparticle engineering process, Evaporative Precipitation into Aqueous Solution (EPAS), was modified to provide improved control over the size of precipitated particles. The improved process, Advanced EPAS, was employed to prepare nanoparticles of the poorly water-soluble drug itraconazole (ITZ). The influence of processing parameters and formulation aspects on the size of suspended ITZ-particles was investigated. The process was shown to be robust such that the size distribution of dispersed nanoparticles was largely independent across the different parameters. In Chapter 3, aqueous nanoparticulate dispersions of the poorly soluble drug mefenamic acid (MFA) were developed and subsequently incorporated into controlled release formulations employing spray-drying. Release of MFA from spray-dried formulations was sustained and complete demonstrating the feasibility of using nanoparticulates for the preparation of controlled release systems. In Chapter 4, the nanoparticle engineering process, Rapid Freezing (RF), was utilized to produce nanostructured, amorphous aggregates of the poorly water soluble drug ketoprofen (RF-KET). The stability of RF-KET against recrystallization was improved through the deposition of a hydrophobic plasma-polymerized film. The coating presented an effective barrier against surface mobility and moisture uptake resulting in enhanced stability of RF-KET for up to six months at accelerated storage conditions as compared to three days for uncoated RF-KET.