Projects and Grants per year
Grants and Contracts Details
Description
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.
Status | Finished |
---|---|
Effective start/end date | 10/1/15 → 8/31/18 |
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Projects
- 1 Finished
-
I/UCRC Phase II: Collaborative Research: Center for Pharmaceutical Development (CPD)
Munson, E. (PI), Anderson, B. (CoI), Dziubla, T. (CoI) & Bummer, P. (Former CoI)
10/1/15 → 8/31/18
Project: Research project