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.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ukzn/oai:http://researchspace.ukzn.ac.za:10413/5017 |
| Date | January 1997 |
| Creators | Moopanar, Kevindren Ramachandran. |
| Contributors | Dangor, C. M. |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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