A pilot study on quality of artesunate and amodiaquine tablets used in the fishing community of Tema, Ghana

Abstract

BackgroundThe ineffectiveness of artesunate and amodiaquine tablets in malaria treatment remains a health burden to WHO and governments of malaria-endemic countries, including Ghana. The proliferation of illegitimate anti-malarial drugs and its use by patients is of primary concern to international and local drug regulatory agencies because such drugs are known to contribute to the development of the malaria-resistant parasites in humans. No data exist on quality of these drugs in the fishing village communities in Ghana although the villagers are likely users of such drugs. A pilot study on the quality of anti-malarial tablets in circulation during the major fishing season at a malarious fishing village located along the coast of Tema in southern Ghana was determined.MethodsBlisterpacks of anti-malarial tablets were randomly sampled. The International Pharmacopoeia and Global Pharma Health Fund Minilab protocols were used to assess the quality of anti-malarial tablets per blisterpacks allegedly manufactured by Guilin Pharmaceutical Co Ltd, China (GPCL) and Letap Pharmaceuticals Ltd, Ghana (LPL) and sold in chemical sales outlets at Kpone-on–Sea. Ferric chloride and cobaltous thiocyanate tests confirmed the presence of active ingredients in the tablets. A confirmatory test for the active ingredient was achieved with artesunate (ICRS1409) and amodiaquine (ICRS0209) reference standards. A high performance liquid chromatography analysis confirmed the amount of artesunate found in tablets.ResultsBased on the International Pharmacopoeia acceptable range of 96/98 to 102% for genuine artesunate per tablet, 10% [relative standard deviation (RSD): 3.2%] of field-selected artesunate blisterpack per tablets manufactured by GPCL, and 50% (RSD: 5.1%) of a similar package per tablet by LPL, passed the titrimetric test. However, 100% (RSD: 2.2%) of amodiaquine blisterpack per tablet by GPCL were found to be within the International Pharmacopeia acceptable range of 90 to 110% for genuine amodiaquine in tablet, whilst 17% of a similar package per tablet by LPL failed spectrophotometric testing.ConclusionInadequate amounts of artesunate and amodiaquine detected in the tablets suggest that both pharmaceutical companies may not be following recommended drug formulation procedures, or the active pharmaceutical ingredients might have been degraded by improper storage conditions. Thus, drugs being sold at Kpone-on-Sea, Ghana may likely be classified as substandard drugs and not suitable for malaria treatment.

Development of a simple and specific direct competitive ELISA for the determination of artesunate using an anti-artesunate polyclonal antiserum

“…Thus, it is important to quantify the amount of active ART in drug tablets. HPLC methods are currently used to estimate the amount of active ART [22]. However, the use of methods requiring expensive equipment and trained technicians is restricted to well-equipped laboratories and thereafter is unfeasible in many malaria-endemic areas where quantification of the amount of ART in tablet samples is needed.…”

A systematic review of counterfeit and substandard medicines in field quality surveys

“…68 The TLC analysis technique is limited by its inability to detect higher than 80% of API concentration in medicine samples 41 which has been evident to exist in previous studies. 31,41,44,46,50,52,53,61,63,66,70,73,[76][77][78]87,91,93 It is therefore possible that the prevalence of SSFFC medicines in South America could be higher than the reported figures if more sophisticated chemical techniques for the quantification of API% content were used, such as high-performance liquid chromatography. Another study reported problems with low API% on a range of medicines procured from Mexico; of particular importance are some narrow therapeutic index medicines such as warfarin and levothyroxine.…”

“…12,33,35,40,46,56,62,80,86,88 Package inspection was more popular than authentication, being reported in 39/66 (59%) of studies, with the majority reporting obvious spelling errors and basic label information (medicine name, dosage, manufacturer, expiry date, and lot number), as shown in Tables 1, 2 (61%) and 19/66 (29%) of studies, respectively (Tables 1, 2, and 4). Other chemical analysis methods were reported such as color reaction tests, 39,40,43,48,49,52,[54][55][56][57]66 spectroscopic techniques, 12,43,[54][55][56]58,61,63,69,71,72,75,79,92 and titration, 47,50,52,59,63,73 but remain less frequently used. Moreover, physical analysis tests were performed in 39/66 (59%) of the studies (Tables 1, 2 and 4).…”

“…The most common physical tests reported were disintegration and/or dissolution tests in 36/39 (92%) cases (Tables 1, 2, and 4). Other less frequently used physical analysis tests include content uniformity, 33,42,43,45,66 weight measurement, 33,35,42,47,52,57,60,63,65,67,73 hardness, 32,65,73 and friability 32,43,60,65,73 tests. Interestingly, only six studies (9%) reported all four types of analysis in an attempt to clearly identify and classify the type of SSFFC problem, where present, in any medicine sample.…”

Healthcare professionals’ perspective can guide post-marketing surveillance of artemisinin-based combination therapy in Uganda

“…The proliferation of substandard and falsified artemisinin-based combinations (SF ACT medicines) is of global concern and has disproportionately affected highly malaria-endemic Southeast Asian and sub-Sahara African (SSA) countries [1][2][3][4]. Up to 66% of drugs studied in SSA, in a recent quality study, were found to be substandard [5]. Newton et al showed that SF ACT medicines account for 38% of artemisinin-based combinations in the private sector market in Uganda [6].…”