Multi-scale analysis and simulation of powder blending in pharmaceutical manufacturing

A Multi-Scale Analysis methodology was developed and carried out for gaining fundamental understanding of the pharmaceutical powder blending process. Through experiment, analysis and computer simulations, microscopic particle properties were successfully linked to their macroscopic process performance. This work established this micro-to-macro approach as a valid way to study unit operations in the pharmaceutical manufacturing of solid dosage forms. The pharmaceutical materials investigated were anhydrous caffeine, lactose monohydrate and micro- crystalline cellulose (MCC). At the macroscopic level, blending experiments were conducted in mini-scale lab blenders using the Light-Induced Fluorescence (LIF) technique. Effects of operating parameters on blending kinetics were systematically evaluated. It was found that the time required to reach a homogeneous mixture (thg) increased with blender fill volume (FV) and decreased with blender rotation rate (RPM). It was also found that MCC, as an excipient, always took longer time to mix with caffeine than lactose. At the microscopic level, force interactions - cohesion/adhesion and friction - were measured directly at the single particle level with Atomic Force Microscopy (AFM).

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Ngai, Samuel S. H

Advisor dc:contributor.advisor

• Charles L. Cooney.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/33720

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/33720