Bioavailability assessment of some locally manufactured chloroquine phosphate tablets
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Date
2005-11-03
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Abstract
Chloroquine used to be the first choice antimalarial drug for the treatment of malaria but has now been replaced by artesunate-amodiaquine combination due to about 30 percent treatment failures experienced in Ghana. While drug resistance can cause treatment failure, not all treatment failure is due to drug resistance. Many factors can contribute to treatment failure including; incorrect dosing, non-compliance with duration of dosing regimen, poor drug quality, drug interactions, poor or erratic absorption and misdiagnosis. Thus, to investigate whether treatment failure was due to poor drug quality and poor absorption three brands of chloroquine phosphate tablets with poor dissolution profiles were selected and in vivo bioavailability studies of the three brands and a reference brand were conducted in six healthy subjects in a crossover method and the amount of unchanged chloroquine phosphate in the urine voided by these subjects over a 24-hour period determined and quantified by RP-LC.
Development of new, more reliable or more sensitive method of analysis is a concern of utmost important in the field of drug analysis. In this regard a simple, specific, a sensitive and rapid method has been developed and validated for the determination of chloroquine phosphate in human urine. The assay consisted of RP-LC with UV detection at a wavelength of 333nm at ambient temperature with a mobile phase combination of methanol (99.8%): 0.lM Na H2P04 buffer (pH 3): 2.5%V/ perchloric acid (24: 75.75:
0.25). Amodiaquine hydrochloride was used as the internal standard. Total chromatographic time was approximately 11.5 minutes. The method was found to be cost- effective because the amount of solvent used per elution time was less. The limit of quantification was 0.001%w/. The method was used to analyze some brands of chloroquine phosphate tablets and validated using the standard titrimetric and UV methods for the analysis of chloroquine phosphate.
The products were designated as TX, TY and TZ respectively from Letap pharmaceuticals Phyto-Riker pharmaceuticals, Dannex Ltd and product R from Astra Zeneca UK Ltd as the reference. All the products used for the work except product TZ passed the specifications described in the BP 2002.
Pharmacokinetic parameters such as the average cumulative amount of unchanged drug excreted, the time for peak urinary excretion, and the mean peak urinary excretion rate were assessed to characterize bioequivalence.
In the analysis of chloroquine phosphate in the urine of six healthy subjects an average of 8.74, 8.10, 10.38 and 10.65 percent of the administered dose for test products TX, TZ, TY and reference product R respectively were excreted in 24 hours. Only products TX and TY were bioequivalent with the reference product R with relative bioavailabilities of 82.11 and 97.52 percent respectively that of TZ failed with relative bioavailability of 76.11 percent.
Statistical analysis also showed that there was a significant difference between the means of the time for peak excretion rate obtained for the test product TZ and the reference product R. However, there was no significant difference between the standard deviations and the means of all the pharmacokinetic parameters investigated for test products TX and TY with reference product R.
Description
A thesis submitted to the College of Health Sciences in partial fulfilment of the requirements for Master of Science degree in (Pharmaceutical Analysis and Quality Control), 2005