2026-09-23T20:17:34.959864667Zhttps://repository.nwu.ac.za/server/oai/requestoai:repository.nwu.ac.za:10394/391382022-05-19T15:14:46Zcom_10394_26463col_10394_26476
Kapp, C.J.
Park, Maria Magdalena Johanna Von Wielligh
2022-05-19T12:58:34Z
2022-05-19T12:58:34Z
1978
http://hdl.handle.net/10394/39138
MSc , North-West University, Potchefstroom Campus
The objectives of this investigation were to:
i) develop a stability indicating method for
paracetamol tablets;
ii) formulate and prepare different paracetamol
tablets and to compare the bioavailability
and physicopharmaceutical properties of
these tablets and presently registered
tablets;
iii) evaluate the stability of the above mentioned
tablets and to come to a conclusion on the
quality after a period of storage;
iv) come to a conclusion on the stability differences
between the formulae;
v) evaluate the effect of e levated temperature
and humidity conditions on the rate of degra=
dation of paracetamol in solid dosage form.
A review of the physicalcharacteristic~ pharma=
cological activity, metabolism and excretion of
231
paracetamol is given.
The effect of humidity, temperature, light and
air oxidation on the stability of paracetamol is
discussed. In humid surroundings the process of
hydrolysis is taking place at an accelarated
rate and this is catalized by elevated temperatures.
The resulting degradation product, p-aminophenol
and impurity, p-chloroacetani lide that may be
present during the synthesis of paracetamol, are
both toxic (Woodbury, 1975). The degradation
of paracetamol is a process of the first order
(Koshy & Lach, 1961).
A review of the published methods for analysis
of paracetamol as raw material, in phannaceutical
preparations and in biological material, are
given.
The factors involved in the preparation of para=
cetamol in solid dosage fonn as well as in the
in vitro and in vivo evaluation of the tablets,
are discussed.
The experimental section of this investigation
comprises the developing of a stability indicating method for the de termination of unchanged
paracetamol and its degradation products, the formulation, preparation and evaluation of various tablet
formulae and a stability study. Four methods of
analysis have been investigated for use as a stability
indicating method, namely gas chromatography, thin
layer chromatography, ultraviolet spectrophotometry
and colorimetry. A colorimetric-ultraviolet spectraphotometric method was developed and employed in the
stability study.
Seven tablet formulae were prepared and together with
the two registered formulae subjected to physicopharmaceutical
evaluation. The in vitro evaluation
of the tablets was used to select three formulae,
which together with the two registered formulae were
subjected to in vivo evaluation. Variation in
espesially rate of dissolution and disintegration
time, became apparent during t he in vitro testing .
No significant differences bet ween the formulae could
be found with regard to the in vivo behaviour.
A stability study was performed and tablets from
each of the different formulations were subjected to
conditions of constant elevated temperatures and
relative humidities . Minimum and maximum relative
humidities of 54 , 4 and 81, 2% respectively and
minimum and maximum temperatures of 50° and 70°c
respectively, were kept.
An initial assay was performed by making use of
colorimetric-ultraviolet-spectrophotometric
method and the determination repeated after periods
of 1, 3 and 4 months.
The following deductions could be made: the
degradation of paracetamol in solid dosage form,
when kept under conditions applied in this investigation, averages 15%; no significant differences
could be detected regarding the stability data of
the various formulae and the effect of elevated
temperature and humidity , was accelarated rate of
hydrolysis.
The average half life for paracetamol in solid
0 dosage form was calculated as 3,8 years at 25 C and
relative humidity of 81 , 2%.
Masters
other
North-West University (South-Africa)
Die stabiliteit van parasetamol in vaste doseringsvorme
Thesis
open.access