10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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A Binary Nucleation Model for Engineering Layered Drug Nanoparticles from Air Jet Atomization of Two-Solute Solutions
Y.S. MAYYA, Chandra Venkataraman, Indian Institute of Technology Bombay
Abstract Number: 332 Working Group: Aerosol Modeling
Abstract It is well-known that the use of nanoparticles for drug delivery offers several advantages in terms of targeting the delivery and enhancing bioavailability, half-life and stability in biological systems. Encapsulation of drugs in lipids often enables multidrug (hydrophobic and hydrophilic) therapy and controlled release. Aerosol synthesis of layered, lipid-encapsulated drug nanoparticles, with surface stabilizing molecules, has recently been carried out through spontaneous self-assembly in evaporating sub-micron droplet aerosols generated through air-jet atomization of two-solute solution precursors. Air-jet atomization offers higher throughput rates of nanoparticles, over that from traditional electrospray systems, with coaxial geometries, used for layered nanoparticle preparation. A major question that needs to be addressed is whether it is possible to engineer encapsulation, in a selected lipid-drug system and control layer thickness and composition. In a recent theoretical paper, (Sapra et al. 2017) an attempt was made to answer this question by introducing a novel concept of "lipid-drug demarcation diagrams". The theoretical approach employed above consists of an evaporating droplet-solute diffusion model combined with a prescription of critical supersaturation solubility (CSS) for crust formation. Critical supersaturation solubility is determined from the criterion proposed by He et al. (2006), invoked from classical nucleation theory. A parameter space was defined of material properties and process conditions for the formation of a layered structure with the preferential accumulation of the lipid in the outer layer. The developed diagrams can guide the selection of solvents, lipids, and processing conditions such that drug loading and lipid encapsulation are optimized in large scale production of layered nanoparticles. However, the CSS concept is applicable strictly for single solute system. For nucleation in a two-solute system, the attainment of crust for one species will be influenced by the activity of the other. To take this aspect into account, it is then necessary to address the problem from binary nucleation framework. In this work, we develop a theory that combines binary nucleation process (Seinfeld and Pandis, 2006) inside the droplet, with the evaporating droplet-solute diffusion model model. It involves the formation of a compound two-species critical nucleus that rapidly grows into a crust by surface growth mechanisms. The composition of the outer layer is now quantified in terms of relative enrichment of lipid over the drug. The model predicts the kinetic growth of this layer until the porosity decreases to a level when the evaporation rate slows down considerably, when the model terminates to calculate nanoparticle diameter and shell thickness. Although complex, the model not only predicts the crustal diameter, but also delineates the propagation of solidification inside the particle along with the evolution of composition. Details will be presented substantiating improvement of this approach over existing solute diffusion models.
References: Sapra, M., Y.S. Mayya and C. Venkataraman, Colloids and Surfaces B: Bio-interfaces. 154, 178-185 (2017). He, G.W., V. Bhamidi, R.B.H. Tan, P.J.A. Kenis, C.F. Zukoski, et al. Crystal Growth and Design, 6, 1175–1180 (2006). 3. Seinfeld J.H. and Pandis, S.P. Atmospheric Chemistry and Physics : From Air Pollution to Climate Change, John Wiley, (2006 ).