Ghori, Muhammad U. (2014) Release kinetics, compaction and electrostatic properties of hydrophilic matrices. Doctoral thesis, University of Huddersfield.

This thesis illustrates the behaviour of cellulose ethers during powder processing, compaction and drug release, as these are frequently employed in the fabrication of compressed hydrophilic matrices. The handling operations can give rise to the electrification of powder particles, which can affect the end product‘s quality. Controlling the parameters which can dictate the quality of compressed matrices is an ambition inherent in the development of pharmaceutical formulations. Thus, the aims and objectives of this thesis were to firstly study the electrostatic, surface adhesion, dissolution and compaction properties of plain polymers and model drugs. Secondly, binary mixtures of fixed drug to polymer ratios were made in order to investigate the effect of polymer concentration and physico-chemical attributes (particle size, chemistry and viscosity) on the tribo-electric charging, surface adhesion (SA), swelling, erosion, drug release kinetics and compaction properties of model drugs.
It can be discerned that the both drugs charged negatively, whereas the methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) particles charged positively. The physico-chemical properties associated with MC and HPMC, such as particle size, chemical heterogeneity and molecular size of cellulose ethers all have a significant effect on charging and adhesion behaviour of plain MC and HPMC particles. Moreover, the concentration, particle size, chemical heterogeneity and molecular size of MC/HPMC all significantly affect the charging and SA propensity of the model drugs studied.
The swelling and dissolution results confirm that the extent and rate of swelling, swelling exponent, dissolution rate and drug release kinetic parameters were affected by physico-chemical attributes (concentration, particle size, substitution and viscosity) of MC/HPMC and drug solubility. The mechanism of swelling and drug release was found to be anomalous. However, it inclined towards more diffusion-oriented swelling/drug release with higher MC/HPMC levels, viscosity, Hpo/Meo substitution ratios, drug solubility but smaller MC/MC particle size.
The matrix erosion results obtained from newly developed phenol-sulphuric acid assay (PSA) method confirmed that the solubility of the drug, and levels of HPMC in a particular matrix tablet, significantly affect the matrix erosion rate and the results were similar to those determined using the much more labour-intensive gravimetric method. Moreover, the combination of conventional UV drug analysis technique and PSA assay can be used to simultaneously quantify the matrix erosion, polymer dissolution and drug release kinetics in a single set of experiments avoiding the need for separate studies.
The compaction results confirmed that the FBP has poor compaction as compare to THP. The particle size, substitution ratios and molecular size of MC/HPMC affect the compaction and consolidation behaviour of plain MC/HPMC compacts. Furthermore, it can be noticed that the concentration and physico-chemical attributes (particle size, chemistry and molecular size) of MC/HPMC have a significant influence on the densification and consolidation process of hydrophilic matrices.
In summary, the information obtained can be used in the future to develop and adopt strategies for development and further optimization of compressed hydrophilic matrices.

Thesis_(Muhammad_Ghori)_-_final.pdf - Submitted Version

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