Scope: Supplement: I/UCRC: Center for Pharmaceutical Development

  • Munson, Eric (PI)
  • Defrese, Matthew (CoI)

Grants and Contracts Details


1. The veteran student will pursue practical and theoretical approaches to understand the atomization and particle formation processes during spray drying of amorphous solid dispersions (ASDs). a. Droplet size distribution will be investigated as a function of the feed solution and ASD composition properties along with varying operating conditions such as commonly used spray nozzles, atomization air flow, and temperature conditions. The droplet size distributions produced in these investigations will be characterized by the Malvern Spraytec laser diffraction system coupled with high speed imaging. Models for prediction of the droplet mean diameter and span will be developed as informed by dimensionless parameters such as the Weber, Reynolds, and Ohnesorge numbers determined from feed solution properties and operating conditions and validated against the measured experimental data. b. With comprehensive knowledge of formulation and operating conditions on the resulting droplet size distribution, the particle formation process following atomization may then be better understood. Structural and chemical characterization of the resulting bulk and individual particle properties will be investigated with both contemporary and novel application of tools (such as time of flight secondary ion mass spectroscopy, X-ray photoelectron spectroscopy, X-ray computed tomography, and energy dispersive X-ray spectroscopy) for the analysis of ASDs. The novel applications will be evaluated with recommendations for those most suitable for the continued analysis of spray dried particles. c. Characterization of particle properties with known droplet size distributions, feed solution properties, and drying conditions will allow for mapping the interplay of formulation and process parameters on the intermediate drug product attributes. Computational fluid dynamic models will be developed to simulate single particle formation and define the environment in the primary drying unit operation based on heat, mass, and momentum balances. These results will interrogate existing models of particle formation and where appropriate, support the development of novel models best suited for pharmaceutical applications. d. The thermodynamics and length scales of mixing will be explored through the application of Flory-Huggins solution theory of ternary systems to understand how solvent-drug-polymer interactions and polymer solvent quality may influence the heterogeneity or miscibility of spray dried particles. Solvent systems of varying polymer solvent quality and strength of solvent-drug-polymer interactions will be investigated by dynamic light scattering and solution calorimetry with suitable systems selected for spray drying. The resulting dispersions will be assessed by dynamic nuclear polarization solid-state NMR spectroscopy to determine the length scales of mixing and strengths of drug-polymer interactions in the intermediate drug product. e. Dissolution experiments will be designed for amorphous solid dispersions to provide suitable discriminating power capable of assessing failure modes induced by spray drying conditions. These designs will be based on the thermodynamic limits of the crystalline solubility and the maximum concentrations prior to spinodal decomposition. Diffusion flux experiments will be further used to discriminate between free drug concentrations compared to drug retained in alternate physical and solution state structures as dictated by thermodynamic principles.
Effective start/end date10/1/158/31/18


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