Document Type


Date of Award

Spring 5-31-2011

Degree Name

Doctor of Philosophy in Chemical Engineering - (Ph.D.)


Chemical, Biological and Pharmaceutical Engineering

First Advisor

Rajesh N. Dave

Second Advisor

Boris Khusid

Third Advisor

Ecevit Atalay Bilgili

Fourth Advisor

S. Mitra

Fifth Advisor

Bruno Caspar Hancock


Engineered particles, which have undergone surface modification via dry coating, have been previously shown to have improved flow and handling properties. The improvements in these properties can be applied and are very useful for a number of industrial applications, in this case the pharmaceutical industry. This work investigates the effect of dry particle coating to improve the flowability of cohesive active pharmaceutical ingredient (API) powders and their blends. Improving the flow properties of cohesive API powders can significantly improve their handling and subsequent use for pharmaceutical processes such as formulation and manufacturing processing operations. Although it has been shown that these surface modified powders flow better as indicated by reduced angle of repose and faster or more uniform flow out of a funnel, more quantitative methods of characterization are needed to fully understand the mechanism of coating and extent of improvement.

Acetaminophen, ibuprofen and other powders were the APIs considered in this work. They were surface modified via dry coating of nano-additives using several different devices. The study considered the use of both hydrophobic and hydrophilic nano-additives. Since the dry coating process is not easily achieved by simple mixing of the API and nano additives, high and/or sustained levels of shear are required to disperse the silica over the API particle. There is a need to develop a new dry coating process that is reproducible, scalable and continuous so that dry coating can be applied to (1) simplify formulations, (2) enable higher API levels, and (3) improve overall powder and drug product manufacturing performance.

In contrast to previous studies that only employed angle of repose to evaluate flow improvement, in this work various quantitative flow characterization techniques are used to assess the changes in flow properties. In addition to use of MAIC and hybridizer which are batch devices, this work also includes development of continuous dry coating

methodology which is based on a typical pharmaceutical powder processing device, namely comil. The comil is found to be fast and efficient, as it is a continuous process with little loss of material. The comil has also been scaled up to pilot scale, indicating that it could easily be implemented in existing formulation and manufacturing processes.

The powders that have undergone surface modification via dry coating techniques are first analyzed for the extent of coating using scanning electron microscopy (SEM) and then the powders are analyzed for their particle size distribution using the Sympatec Helos/Rodos system under varying dispersion conditions to ensure there was no attrition during the coating process. Additionally, a variety of techniques are employed to characterize the powder flow and bulk handling properties, which are important for large scale pharmaceutical manufacturing. Extensive characterization of the powder's flow properties were performed using both novel methods, such as vibrated packed density, as well as industry standard techniques such as shear testing via the Schulze tester, the Freeman FT4 Rheometer and the Hosokawa Powder Tester. Other powder properties such as bulk and tapped densities are also evaluated. The results of these tests are compared with those for untreated API powders in order to examine the enhancement of the powder properties due to the surface modification. This work also clearly illustrates that the pharmaceutical materials undergo significant attrition if the dry coating devices are not optimized.

This work intends to position dry coating as a platform technology and show that dry coating based surface modification has the potential to become a routine tool for use in pharmaceutical industry to enable better formulations and aid in manufacturing.



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