TitleThe production and stabilization of pharmaceutical nanosuspensions
NameRomanski, Francis S. (author), Tomassone, Maria Silvina (chair), Muzzio, Fernando J (internal member), Shapley, Nina C (internal member), Michniak, Bozena B (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectChemical and Biochemical Engineering,
Drug delivery systems
DescriptionThe production and stabilization of pharmaceutical nanosuspensions has been a recent focus of the pharmaceutical industry where it has been shown that nanosuspensions of poorly water-soluble drugs exhibit a greatly increased dissolution rate, and as a consequence, an increased in vivo bioavailability. Accordingly, the ability to manufacture stable pharmaceutical nanosuspensions in a fast, safe, and predictable manner would be highly advantageous. However, the small size is not without consequence; the prodigious amount of available surface area in combination with van der Waals forces quickly cause irreversible agglomeration, destroying the desired properties, and thus requiring the use of surfactants for any combination of steric, electrostatic, and kinetic stabilization. As a result, this work focused on two distinct methods for producing pharmaceutical nanosuspensions, as well as the important role that surfactants play in stabilization. In the first method, high pressure homogenization was used to mill suspensions by forcing them through a minute piston gap, where particles were subjected to a combination of shear, cavitation, and grinding. This technique was optimized for use by incorporating excipients for novel formulations in situ with the goal of producing capsules, films, and oral-suspensions. Alternatively, the shortcomings present in all accepted nano-sizing methodologies led to the development of the emulsion precipitation method. In this process, nanoparticles as small as 60 nm were produced by extracting drug nanoparticles from an O/W emulsion made from partially miscible components. It was found that formulations utilizing any one of five contrastive solvents could be used to create nanosuspensions based not on intrinsic drug properties, but rather on droplet size, solvent diffusion, and surfactant choice, rendering this technique arguably the most robust currently available. Finally, the recurrent issue of stability was addressed through a series of molecular dynamics simulations and corresponding experiments to elucidate the molecular phenomena present at the surfaces of nano-scale crystals. Several case studies measured the interfacial binding energy between a surfactant and a crystal surface, where strong interactions were indicative of a longer shelf-life, quenched growth rates, and predictable crystal morphologies. It is hoped, that the culmination of this work will greatly advance our ability to produce, stabilize, and deliver poorly-soluble drugs.
NoteIncludes bibliographical references
Noteby Francis S. Romanski
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.