(373a) Spray Drying of Drug Loaded Nanoparticles with Matrix Forming Excipients

Nanoparticle drug delivery systems are of recent increased interest for applications in both oral and parenteral drug delivery. Typically, nanoparticles are formed in liquid media by precipitation or self-assembly, resulting in a nanoparticle suspension. However, it is often desirable to obtain a dry powder form of the nanoparticles that may be later resuspended in liquid media. The dry powder facilitates efficient storage and transport of the nanoparticle formulation.

One high-throughput method of achieving a dry powder from a liquid nanoparticle suspension is via spray drying. During spray drying, a heated drying gas contacts atomized liquid droplets, promoting fast evaporation of the liquid and resulting in a dry powder. Spray drying is commonly employed in many large-scale processes in the food processing and pharmaceutical industries, notably for the production of dry milk powder. However, in the case of nanoparticle therapeutic formulations, the addition of matrix-forming excipients during spray drying is necessary in order to preserve the integrity of the nanoparticles during the drying process. These excipients result in the formation of micron scale matrix particles containing embedded nanoparticles. When reconstituted in a liquid, the matrix dissolves, thus re-dispersing the nanoparticles.

Here, we present a systematic approach to investigate the use of various matrix materials during the spray drying process, including functionalized cellulose, sugars, and synthetic polymers. We study the effect of matrix former on the size and polydispersity of the spray-dried nanoparticles upon re-dispersion. By varying the mass ratio of matrix former to nanoparticles, we study the amount of matrix former required to prevent nanoparticle fusion and aggregation during the drying process. We employ model nanoparticles to investigate the effect of the nanoparticles on the thermal properties of the resulting matrix particles. Polymer-stabilized core-shell nanoparticles with core materials of varying glass transition temperature are spray dried, and the matrix particles are characterized by calorimetry. We show that the composition of the nanoparticles influences the thermal properties of the matrix particles.