In-Vitro Comparative Evaluation of Different Co-Trimoxazole Tablet Products Obtained From Drug Retail Outlets in Addis Ababa
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Date
2004-02
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Addis Ababa University
Abstract
Evaluation studies provide a means of identifying quality differences between same products
obtained from various manufacturers and quality evaluations are crucial in the era of increasing
resistance to antibacterial agents
The introduction of trimethoprim in combination with sulphamethoxazole constitutes an
important advance in the development of clinically effective antimicrobial agents. In much of the
world the combination of sulphamethoxazole with trimethoprim in the proportion of 5 to 1 is
known as Co-trimoxazole. Co-trimoxazole has been used in a diverse range of infections due to
sensitive bacteria and is widely prescribed for various indications. By virtue of sequential
blockade of microbial folic acid synthesis the antimicrobial combination has excellent in vitro
inhibitory activity against many common respiratory and urinary tract pathogens, as well as many
nosocomial-infecting strains. In patients infected with the human immunodeficiency virus (HIV),
trimethoprim-sulphamethoxazole provides prophylactic and therapeutic potency against
Pneumocystis carinii but at the risk of side effects. Trimethoprim-sulphamethoxazole (TMPSMX)
is also used for treatment of pulmonary and disseminated nocardiosis and some forms of
Wagener’s granulomatosis, as well as for prophylaxis of spontaneous bacterial peritonitis.
Bacterial resistance to trimethoprim-sulphamethoxazole is a rapidly increasing problem and is
exacerbated by use of substandard products. In this work, it is aimed to evaluate the physical
properties and the dissolution profiles of trimethoprim-sulphamethoxazole tablets produced by
ten different manufacturers and are obtained from drug outlets in Addis Ababa.
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Accordingly, the different tablets were evaluated for physical properties (Diameter, thickness,
shape, hardness, friability and disintegration time) and their dissolution profiles were compared
by the USP XXVI paddle method.
The tablets investigated in this study could roughly be grouped as those, which exhibited, delayed
drug release and those, which released the drug contained immediately. The tablets evaluated in
this study differed in many of their physical properties. The average weights ranged from
502.41mg (Bactrim) to 709.98mg (Cotrimol), 480mg being the expected strength of the
combination. The mean disintegration times ranged from 0.17 (±0) minutes (Cotrimoxazole) to
13.05 (±5.24) minutes (Lagatrim).
Nine of the tested products gave an assay value above the lowest limit (93%-107%) specified in
the pharmacopoeia. Assay values greater than the upper limit for sulphamethoxazole was
obtained with four of the evaluated products. One product gave an assay value greater than the
upper limit for both sulphamethoxazole and trimethoprim.
Most of the tablets released the drug contained in an increasing fashion from the 5th minute to the
60th minute with varying proportion of increment. Products obtained from Europe released most
of the drug within the first 5 to 10 minutes. More than 90 % of trimethoprim is released within 5
minutes from Bactrim and Septrin and with in 10 minutes from Lagatrim and Deprim. While
Lagatrim and Septrin released more than 90 % of their Sulphamethoxazole within 10 minutes,
Bactrim and Deprim released their Sulphamethoxazole within 20 minutes. However the European
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and the non-European products differed significantly in their sulphamethoxazole release. Both
products showed a comparable trimethoprim release pattern. All of the tested products released
more than 90% of the trimethoprim after one hour, ranging from 92.81%-Cotreich to 111.77%-
Septrin.
The very long t90% values of Cotreich and Cotrimol (60 & 45minutes respectively) for
trimethoprim, the very long t50% & t90% values of Cotreich (38 and >60minutes respectively) for
trimethoprim and sulphamethoxazole, and the very long t90% values of Cotreich, Cotrimol and
Kanprim (>60 minutes) for sulphamethoxazole indicate that these products could result in lower
rate and extent of bioavailability in the body. Similar problems could be encountered with the
relatively long t90% values of Cotrimoxazole (45minutes) and Oriprim (40minutes) for
Sulphamethoxazole. The smaller amount of sulphamethoxazole and trimethoprim released from
products with delayed release could compromise the in vivo efficacy of these tablets.
Description
Keywords
Antibacterial agents; Co-trimoxazole