ACCELERATED STABILITY AND ANTIMICROBIAL SENSITIVITY STUDIES OF AMOXICILLIN DRY SUSPENSIONS
ABSTRACT
ince its introduction, amoxicillin dry suspension has been
the mainstay for the antibacterial
therapy for paediatric patients. But use of substandard preparation of
antibiotic is one of the most important
causes of microbial resistance. The present study has been carried out to evaluate the quality and stability status
of 10 marketed amoxicillin dry suspensions of
Bangladesh. All the brands were analyzed for their potency using
chemical and microbiological methods
described in the United States Pharmacopoeia and British Pharmacopoeia.
Potency determination was done at three
controlled temperatures - refrigerated, room and elevated (40.C) showed that two samples were over potent but
one sample was substandard out of the 10
samples. The initial potencies of the two samples were within USP range
when freshly reconstituted but after 7
days, at room temperature, potencies deteriorated and came down to 90%. In refrigerated condition, all the
samples remained in good condition and at 40.C, a considerable loss of potencies in all the
samples were observed. Results of microbiological assay also support the results of chemical assay.
The study emphasizes the necessity of routine
inspection, monitoring and evaluation of quality of formulations
containing amoxicillin dry syrup. Keywords: Amoxicillin, dry suspension,
paediatric patients, substandard, reconstituted.
INTRODUCTION
Bangladesh is a developing country where a significant
proportion of the total population lives
down the poverty line and cannot afford for appropriate medical care, adequate
nutrition and proper sanitation (Walsh,
1979). Due to poor sanitation and unhygienic environment microorganisms can grow favorably. Infectious
diseases are therefore the most prevalent diseases here (Chowdhury, 1995; Das, 1994). Among the
infectious diseases, bacterial infections contribute to most of the mortality specially among the
young children (Riley et al., 1983). It has been reported that in every year, 5 million
children die from infectious diseases (WHO, 1997). In order to combat the bacterial infections,
antibacterials are used. In most of the cases, the physicians start antibiotic therapy with penicillin group, for
example ampicillin and amoxicillin. Amoxicillin is available in liquid form such as dry syrups
or powder for suspension. Amoxicillin dry syrup, a paediatric preparation, ranks the first position
in the antibiotic therapeutic class in Bangladesh. Approximately 35.1% of the prescriptions were
found to contain amoxicillin dry syrups (Islam,
1998). Antibiotic resistance has now-a-days become a global health
problem (Kunin, 1983). One of the causes
of microbial resistance includes the use of substandard preparations. The
availability and consumption of
antimicrobial agents without prescription facilitates the development of
MATERIALS AND METHODS
Materials
Collection of samples
The samples of
amoxicillin dry suspension were collected
randomly from the retail medicine shops located at different areas of Bangladesh. Bacterial strains
Six bacterial
strains were collected for the analytical
purposes. The pathogenic strains included Streptococcus pyogenes, Streptococcus viridans, Haemophilus
influenzae, Bacillus cereus, Escherichia
coli, Shigella and Klebsiella Sp.
Analytical methods Potency
determination
Amoxicillin contents
in dry syrups were determined by iodometric
titration method described in the United States
Pharmacopoeia (USP, XXIII, NF, XVIII, 1995a). Moisture content determination
At first 0.5 gm
sample was weighed and then put into a
drying oven for 4 hours at 105C. The bottle was
taken out and weighed again. The
difference of the two values gave the amount
of water in the sample. Thus, the percentage of loss on drying (LOD) was calculated by taking the ratio of
weight of water in the sample and total
weight of the wet sample and by multiplying with 100. % LOD gave the measure of the moisture
content in the sample (Rankell AS, et
al., 1989). pH determination
The pH values of the
freshly reconstituted amoxicillin dry
syrups were measured by using a pH meter.
Determination of sedimentation
volume Sedimentation volume was
determined by taking a definite volume
of the reconstituted sample into a graduated
cylinder and then keeping it undisturbed for 7 days. After 7 days, sedimentation volume (F) was calculated from
the ratio of the final volume (Vf) of
the sediment to the original or initial volume (Vi) of the suspension before settling (Martin A,
1993). Sedimentation volumes were
determined for both freshly reconstituted samples and also for samples undergone storage tests
for two months.
Stability testing
In order to test the
stability of reconstituted suspensions,
the samples were kept at three controlled temperatures, namely room, refrigerated and elevated (40ºC)
temperatures for 7 days. The intact
samples were studied after keeping at 30ºC and 40ºC for two months. All the samples were assayed
chemically by the iodometric method as
described in the USP (USP, XXIII, NF
XVIII, 1995b). In each sample, the decline in concentration appeared to follow the first order reaction.
Following the Arrhenius equation (log K
= log A - Ea /2.303 R. 1/T), log K values at 30 and 40°C were plotted against the respective
reciprocal values of absolute
temperatures , 1/T, when a straight line was obtained. This when extrapolated to give log K25, and from
that shelf-life (t90) of each samples
were determined.
Microbiological assay
In order to mesure
the biopotency, agar diffusion method
was followed as per the British Pharmacopeia (BP, 1995).
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