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Thermal and rheological approaches for the systematic enhancement of pharmaceutical polymeric coating formulations. Effects of additives on glass transition temperature, dynamic mechanical properties and coating performance in aqueous and solvent-free coating process using DSC, shear rheometry, dissolution, light profilometry and dynamic mechanical analysis.
Isreb, Mohammad
Isreb, Mohammad
Publication Date
2013-05-02
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The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
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Accepted for publication
Institution
University of Bradford
Department
School of Pharmacy
Awarded
2011
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Abstract
Additives, incorporated in film coating formulations, and their process
parameters are generally selected using a trial-and-error approach. However,
coating problems and defects, especially those associated with aqueous
coating systems, indicate the necessity of embracing a quality-by-design
approach to identify the optimum coating parameters. In this study, the
feasibility of using thermal and rheological measurements to help evaluate and
design novel coating formulations has been investigated. Hydroxypropyl
methylcellulose acetate succinate (HPMCAS), an enteric coating polymer, was
used as the film forming polymer. Differential Scanning Calorimetry (DSC),
Dynamic Mechanical Analysis (DMA), and Parallel Plate Shear Rheometery
(PPSR) were used to evaluate the effect of different plasticisers on the
performance of HPMCAS. The results illustrate that, for identical formulations,
the DSC and DMA methods yielded up to 40% differences in glass transition
temperature (Tg) values. Moreover, Tg measured using loss modulus signals
were always 20-30 oC less than those measured using tan delta results in DMA
testing. Absolute and relative Tg values can significantly vary depending on the
geometry of the samples, clamp size, temperature ramping rate and the
frequency of the oscillations. Complex viscosity data for different formulations
demonstrated a variable shear thinning behaviour and a Tg independent
ranking. It is, therefore, insufficient to rely purely on Tg values to determine the
relative performance of additives. In addition, complex viscosity results,
obtained using both the DMA and PPSR techniques at similar temperatures, are
shown to be comparable. The results from both techniques were therefore used
to produce continuous master curves for the HPMCAS formulations.
Additionally, step strain tests showed that HPMCAS chains do not fully
III
disentangle after 105 seconds as predicted by the Maxwell model. Finally, in situ aqueous-based coating experiments proved that mixtures of triethyl acetyl citrate and acetylated monoglyceride (TEAC/AMG), even without cooling of the suspension, do not cause blocking of the spray nozzle whereas triethyl citrate (TEC) based formulae did. TEAC (alone or in a combination with AMG) exhibits superior wettability to HPMCAS than TEC/AMG formulations and can be used to enhance the efficiency and film quality of the dry coating process.
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Type
Thesis
Qualification name
PhD