Modeling of adhesion in tablet compression
Abstract
Adhesion problems during drug development and tablet manufacturing are currently addressed by trial-and-error. It is necessary to understand the fundamentals of the interactions between the drug compounds and the punch face in order to anticipate and avoid the adhesion problems. It is hypothesized that the intermolecular interactions between drug molecules and the punch face is the first step in the adhesion process, and that the rank order of adhesion during tablet compression should correspond with the rank order of these energies of interaction. Ibuprofen, ketoprofen and flurbiprofen were chosen as model compounds to test the hypothesis. Computationally, using Cerius2, the rank order of the work of adhesion between ibuprofen, ketoprofen, flurbiprofen molecules and the metal surface was simulated to be −695.847, −718.259, and −442.066 kJ/mol, respectively. The rank order of the interaction between the drug molecule and the iron superlattice decreased in the order: ketoprofen > ibuprofen > flurbiprofen. Experimentally, at the intermolecular level, a thermal analysis approach was used to estimate the work of adhesion between a monolayer of ibuprofen, ketoprofen, flurbiprofen and the inside wall of the DSC pan to be −0.25, −0.18, −0.32 kJ·mol−1, respectively. At the interparticulate level, atomic force microscopy was used to determine the work of adhesion between the iron-coated tip and the ibuprofen, ketoprofen and flurbiprofen surfaces to be −184.1, −2469.3, −17.3 MJ·m −2, respectively. The visual observations and the tablet take-off forces were used as the criteria to judge the adhesion behavior of all three compounds using a compaction simulator for pure drug tablets and an instrumented tablet press for formulated tablets. The rank order of adhesion for pure drug tablets and formulated tablets was found to agree with each analytical estimates. Overall, three novel methods have been developed to investigate adhesion interactions during tablet compression. The rank order of adhesion between a series of profen compounds and the punch face determined at intermolecular, interparticulate and practical levels agree with each other, i.e., ketoprofen > ibuprofen > flurbiprofen. Molecular simulation can predict potential adhesion in the production environment.
Degree
Ph.D.
Advisors
Morris, Purdue University.
Subject Area
Pharmaceuticals
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