|dc.description.abstract||The aim of the present study was to formulate oral modified release matrices of diclofenac
sodium, using the Eudragit® polymers. In addition to the formulation processes, numerous
variables had to be investigated, which included dissolution variables, formulation variables,
and processing variables.
The application of the tabletting technique as well as the use of Eudragit® polymers to modify
the release of diclofenac sodium is motivated at the outset. A comprehensive review of
modified drug release, the use of the tabletting methodologies and the application of
Eudragit® polymers are presented. In-process quality control tests as well as the mechanisms
and interpretation of the dissolution process are outlined. Diclofenac sodium, a potent
nonsteroidal anti-inflammatory drug, was used in the present study, hence a brief review of
this drug is also presented.
The direct compression as well as the wet granulation tabletting methods were investigated.
The major limitation of the direct compression method was found to be the lack of suitable
flow properties of the powder blend. The wet granulation technique however, was
successfully employed to prepare various diclofenac sodium Eudragit® matrix tablets. All
tablets were prepared to contain 100 mg diclofenac sodium. The optimisation process was
shown to be an integral procedure in influencing the matrix characteristics. In addition, it
was shown that drug release was significantly influenced by different types and
concentrations of Eudragit® polymers.
A specific formulation was selected to investigate the integrity of the matrices produced by
the wet granulation technique. The drug release profile of a commercially available modified
release preparation containing diclofenac sodium viz. Veltex® 100 CR (reference standard)
was also obtained. A comparison of the drug release profiles of Veltex® 100 CR capsules
and the selected formulation showed them to be markedly dissimilar. Hence, a strong
motivation is provided for rationalising the selection of the particular formulation in the
present study, that was shown to release diclofenac sodium optimally. The selected
formulation was prepared using a combination of the Eudragit® RL and Eudragit® RS
In vitro dissolution studies on the selected as well as various other formulations demonstrated
the wet granulation method to be both predictable and reproducible. However, absolute drug
release independency of dissolution methods, media and agitation rates was unattainable.
Furthermore, drug release was shown to be pH dependent.
The selected formula was subjected to certain formulation and processing variables. An
increase in the concentrations of lactose and starch was shown to increase drug release.
Different types of diluents were also shown to influence drug release from the tablets. The
method of incorporation of the lubricant, magnesium stearate, was investigated.
Compression studies demonstrated the susceptibility of the tablets to changes in drug release
behaviour and morphological characteristics as the hardness was varied.
X-ray diffraction studies demonstrated that the processes of granulation and compression did
not promote any atomic rearrangement of the drug and Eudragit® polymers. Scanning
electron microscopy was useful in investigating the integrity and surface morphology of
newly formulated as well as stored samples, while energy dispersive x-ray microprobe
analysis adequately revealed the elemental composition of the tablets.
The selected formulation was shown to be stable at room temperature (21 ±1°C) and low
temperature (5± 1°C), while storage at 37°C with 80% relative humidity and 40°C
demonstrated significantly decreased drug release behaviour during short term (3 months)
stability testing. Tablet hardness evaluated during the stability testing showed that there were
virtually no differences in tablet hardness between the room temperature and low temperature
samples, while tablets stored at 37°C with 80% relative humidity and 40°C hardened
considerably. However, tablet potencies and the moisture content of the samples were not
significantly influenced during the storage period.
In addition to usual observations and mathematical manipulation, some of the data generated
from this study were also evaluated statistically.||en