Enhancing the delivery of poorly water soluble drugs using particle engineering technologies

A growing number of potential drug candidates display poor bioavailability related to poor water solubility of the drug molecules in biological fluids. Poorly water soluble drugs require an appropriate technology to engineer particles with enhanced physicochemical properties and deliver it to desired targets in the body. Particle engineering technologies such as evaporative precipitation into aqueous solution (EPAS), controlled precipitation (CP) and ultra-rapid Freezing (URF) were developed to enhance drug dissolution and bioavailablity through the production of stabilized drug nanoparticles and microparticles. The physicochemical properties of nanoparticles and their behavior on exposure to physiological media are greatly dominated by their primary particle size, morphology and surface characteristics.;Both EPAS and CP are nucleation technologies which involve the precipitation of drug from an organic solution into aqueous solution, resulting in rapid nucleation rates and the formation of small stabilized particles. These technologies are different from one another in the type of solvent system and in the specific nozzle mixing (or dispersing) design. The challenge of these technologies is that during the precipitation procedure the growing of the nucleating drug particles must be limited by use of a stabilizer in order to control the particle size.;In contrast to the precipitation technologies, URF utilizes rapid freezing of a drug solution to engineer porous amorphous drug/excipient particles with high dissolution rates. The flexibility of URF provides the potential for the production of particles with a wide array of drug and various dosage forms such as oral, injection, and inhalation. For lung transplant, administering high surface area compositions via pulmonary administration that have been manufactured using nanoparticle technologies represents new potential opportunities to achieve high bioavailability at the target organ. The effect of the differences in the properties of these two types of particles on supersaturation (amorphous vs crystalline) and how it impact on drug absorption were evaluated. Mice were dosed with the inhaled nebulizer dispersions and the lung and whole blood concentrations were studied. Nanostructured aggregates containing amorphous or crystalline nanoparticles of tacrolimus produced by URF showed to be effectively aerosolized in an aqueous dispersion by nebulization.