Date of Award

Fall 2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Materials Science and Engineering - (Ph.D.)

Department

Committee for the Interdisciplinary Program in Materials Science and Engineering

First Advisor

Kamalesh K. Sirkar

Second Advisor

Robert Pfeffer

Third Advisor

San Kiang

Fourth Advisor

Piero M. Armenante

Fifth Advisor

N. M. Ravindra

Abstract

Currently, no technique is available to continuously film coat nano-sized drug particles with a polymer to produce large amounts of free-flowing coated particles. In this work, Eudragit RL 100 and Poly (D, L-lactide-co-glycolide) (PLGA) are chosen as the coating polymers; Cosmo 55 (550 nm silica particles), Aerosi l 200 (hydrophilic 12 nm silica), Aerosil R974 (hydrophobic 12 nm silica) and Griseofulvin (10 lam drug particles) are chosen as the host particles. Two novel crystal l izers are designed and fabricated to continuously coat the host particles with different polymers: solid hollow fiber cooling crystallizer (SH FCC) and porous hollow fiber antisolvent crystallizer (PH FA C).

In the SH FCC-based crystallization/cooling method, the polymer solution containing a suspension of submicron particles flows in the lumen of a solid non-porous polymeric hollow fiber. Controlled cooling of the polymer solution by a coolant on the shell side of the hollow fibers allows for polymer nucleation on the surface of the particles; the precipitated polymer forms a thin film around the particles, the thickness of which can be varied depending on the operating conditions. In the PH FA C based crystallization method, an acetone solution of the host particles containing the dissolved polymer is passed through the shell side of a membrane module containing many porous hollow fiber membranes. Through the lumen side of the hollow fiber membranes, the anti-solvent water are passed at a higher pressure to inject water jets through every membrane pore in the fiber wall into the shell-side acetone feed solution creating an extremely high level of supersaturation and immediate crystallization. The host particles get coated by the precipitating polymer in the PHFAC module. For the coating of Griseofulvin (GF) drug particles, GF first precipitates from the solution in the PHFAC module due to the addition of anti-solvent water, subsequently GF crystals get coated by the precipitating polymer.

Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectrometry (EDS), laser diffraction spectroscopy (LDS) and thermogravimetric analysis (TGA) are all used to characterize the coatings. To study the properties of the coated drug crystals, X-Ray Diffraction (XRD), Raman spectroscopy, and dissolution tests are implemented. These results indicate that a uniformly coated, free- flowing product is successfully developed under appropriate conditions by both the SHFCC and the PHFAC method; the coated drug particles can be potentially used for controlled release of the drug; such a process may be easily scaled up.

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