Microstructural investigation of tablet compaction and tablet pharmacological properties

In current tablet manufacturing processes, there is a knowledge gap concerning material transformation and the subsequent impact on tablet properties; this gap presents a barrier to rational formulation / process design. In this study, it was hypothesized that the understanding of tablet microstructure is pivotal in bridging our knowledge about the materials, the manufacturing process, and the tablet properties. A series of X-ray micro computed tomography (microCT) characterization methods were developed to untangle material interactions during tablet manufacturing process, leading to an interpretation of tablet compaction mechanisms through 3-D representation of microstructural features. Numerical simulation of liquid intrusion based on microCT data was utilized in calculating tablet microstructure permeability, introducing a novel parameter for characterization of tablet dissolution properties. A tablet holder was designed and used in combination with paddle dissolution test to investigate tablet dissolution process, enabling the classification of dissolution mechanisms and identification of correspondent formulation design strategies. When incorporated with permeability results, a quantitative dissolution model capable of separating the contributions from disintegration and surface dissolution was derived. The dissection of the dissolution process provides a scientific framework supporting the Quality by Design paradigm for product and process development. . This work provides a strategy for building an integrated formulation design and characterization system incorporating microstructural analysis. It opens up an approach in which microstructure becomes a critical target for design and optimization.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2010

Author dc:creator

• Mao, Kangyi

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/1721.1/62108

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/62108