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Formulation and evaluation of modified release eudragit® matrices containing diclofenac sodium.Hurbans, Nivriti. January 1998 (has links)
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
polymers.
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. / Thesis (M.Sc.)-University of Durban-Westville, 1998.
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Formulation, evaluation and characterization of an oral modified realease naproxen sodium preparation.Moopanar, Kevindren Ramachandran. January 1997 (has links)
The motivation for the present study is systematically presented and the aims and objectives
of the study are clearly defined. A comprehensive review on modified release drug delivery
has been presented to provide the basis for the meltable aqueous dispersion technique as an
approach to the formulation of a multiple-unit oral modified release drug delivery system.
In addition, a brief discussion on the theory of dissolution testing and the mechanisms and
interpretation of the dissolution process has been presented. Naproxen sodium, a potent
non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic activity
employed in the study, has been briefly discussed.
In the present study, the coacervation phase separation technique utilizing ethylcellulose
was initially investigated but proved unsuccessful in producing a formulation displaying
suitable drug release characteristics. Subsequently, the meltable aqueous dispersion
technique utilizing cetostearyl alcohol was successfully employed to formulate a multipleunit
modified release naproxen sodium preparation containing 550 mg of naproxen sodium.
The use of cetosteary!alcohol, as·a·retarding material, generated modified ·drug release
characteristics as a function of its content. Magnesium stearate (anti-tackiness agent) and
Span 20 and Tween 60· (surfactants) were incorporated in the formulation to optimize
particle size and sphericity. The influence. of various formulation variables on drug release
characteristics were investigated:
An optimized formulation displaying a desirable modified release profile of naproxen
sodium was achieved employing a 1:1 ratio of naproxen sodium:cetostearyl alcohol, 2% m/m .. ..
magnesium stearate, and 1%m/m Span 20 dispersed in a liquid manufacturing vehicle of pH
0.6 containing 2% m/m Tween 60. In vitro dissolution studies on the selected formulation
showed drug release to be predictable and reproducible, dependent on the dissolution
method, agitation rate, and the pH of the dissolution media (i.e. pH-dependent drug
release). The density of the microspheres was shown to decrease as the concentration of
cetostearyl alcohol increased whilst the mean specific surface area increased with
increasing concentrations of cetostearyl alcohol.
Differential scanning calorimetric studies reveals a change in the thermograms which is
suggestive of eutectic formation. Scanning electron microscopy proved useful in evaluating
the integrity and surface morphology of the microspheres as well as in elucidating the drug
release characteristics of the formulation. Energy dispersive x-ray microprobe analysis
revealed the elemental composition of the microspheres to be a composite of the pure
ingredients. X-ray mapping and the line scan depicted the homogenous distribution of drug
within the microspheres and confirmed that the formulation is a matrix-type modified release I'
preparation.
Stability studies were performed on the selected formulation at room temperature
(21 :t 1°C), 40°C, 37°C with 80% relative humidity, and at low temperature (5 :t 1°C). The
shelf-life of the selected formulation was determined to be 1.29 years. Applying the data to
five different kinetic models to investigate the drug release mechanisms showed that first order
and cube-root release characteristics were exhibited by the microspheres. / Thesis (M.Sc.)--University of Durban-Westville, 1997.
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