TABLE 8.
Studies regarding substandard/counterfeit antiparasitic agentsa
| Yr/country(ies) (reference) | Category of drugs studied (n) | Method(s) of detection of low-quality drug | Results | Characteristics of counterfeit/substandard drugs |
|---|---|---|---|---|
| 2012/Ghana (88) | Artemisinin-based antimalarial medicines, tablets: artesunate, amodiaquine, artemether-lumefantrine | Colorimetry, TLC, quality assessment tests (uniformity of mass, crushing strength, disintegration time, % content of active pharmaceutical ingredients) | All 14 (100%) of artemisinin-based antimalarial medicines were substandard/counterfeit | Reduced content of AI, increased content of AI, wt variation outside pharmacopoeial limits, reduced dissolution and stability |
| 2012/South American countries (157) | Antimalarial drugs, tablets: artesunate, chloroquine, doxycycline, primaquine and quinine, SP (1,663) | Visual and physical inspection, disintegration tests, TLC, HPLC | 193/1,663 (11.6%) of antimalarials were of low quality; most of these drugs (8.6%) did not pass inspection or had expired. | Inappropriate packaging and labeling, reduced content of AI, reduced dissolution and stability |
| 2012/Angola, Brazil, Cameroon, Central African Republic, Chad, Congo, Ethiopia, Guinea Bissau, Guinea Conakry, India, Kenya, Madagascar, Malawi, Rwanda, Uganda (111) | Antimalarial drugs (17) | UV-visible spectrophotometric assay | 6/17 (35%) of antimalarial drugs were counterfeit | Reduced dissolution and stability |
| 2011/India (113) | Antimalarial drugs, tablets: artesunate (NR) | HPLC, mass spectrometry | Approximately 80% of artesunate tablets were substandard/counterfeit | Reduced dissolution and stability, reduced content of AI, increased content of AI, inappropriate packaging/labeling |
| 2011/Cameroon, Ghana, Kenya, Nigeria, Tanzania (88) | Antimalarial drugs, tablets: SP, sulfamethoxy-pyrazinepyrimethamine, artemisinin-based combination (267) | Quality testing | 28.5% of drugs were substandard/counterfeit | Reduced content of AI, increased content of AI, no AI, wt variation outside pharmacopoeial limits, impurities, reduced dissolution and stability |
| 2009/Uganda, Madagascar, Senegal (89) | Antimalarial drugs, tablets: artemisinin-based combination, SP (188) | Quality testing | 32% of drugs were substandard/counterfeit | Reduced content of AI, increased content of AI, no AI, wt variation outside pharmacopoeial limits, impurities, reduced dissolution and stability |
| 2010/Nigeria, Ghana (161) | Antimalarial drugs, tablets: SP, amodiaquine, mefloquine, artemisinin | Mini-lab tests, TLC, disintegration tests | The overall rate of substandard antimalarials was reduced significantly by >30% within 3 years | Reduced dissolution and stability, reduced content of AI |
| 2009/India (117) | Antimalarial drugs, tablets: chloroquine (119) | TLC, disintegration and dissolution tests | 7% of chloroquine tablets were substandard/counterfeit | Reduced dissolution and stability, inappropriate packaging, reduced amt of AI |
| 2009/Nigeria (164) | Antimalarials, tablets: artesunate (15) and amodiaquine (5) | Subjective physical assessment of products, TLC, disintegration and dissolution tests | 66.7 % of the 15 studied artesunate tablets were substandard/counterfeit, 1 (20%) of the 5 studied amodiaquine tablets was substandard/counterfeit | Reduced dissolution and stability, inappropriate packaging, reduced amt of AI, increased content of AI |
| 2009/Nigeria (82) | Antimalarials, tablets: artesunate, dihydroartemisinin, SP, quinine, chloroquine (225) | HPLC and dissolution test; U.S. Pharmacopeia standards were used | 37% of drugs were substandard/counterfeit | No AI, wrong AI, reduced amt of AI |
| 2008/Burkina Faso (158) | Antimalarials, tablets: chloroquine, SP, quinine, amodiaquine, artesunate, artemether-lumefantrine (77) | HPLC and dissolution test; European pharmacopeia standards were used | 32/77 (42%) drug samples were found to be of poor quality | Inappropriate packaging, reduced amt of AI, reduced dissolution and stability, no AI |
| 2008/Kenya, Ghana, Nigeria, Rwanda, Tanzania, Uganda (162) | Antimalarials, tablets: amodiaquine, artesunate, artemether, artemether-lumefantrine, dihydroartemisinin, mefloquine, SP (210) | TLC and dissolution tests | Overall, 35% of tested drugs were substandard | Inappropriate packaging, expired, reduced dissolution and stability |
| 2008/Cambodia, Lao PDR, Myanmar (Burma), Vietnam (159) | Antimalarials, tablets: artesunate (391) | HPLC, mass spectrometry | 195/391 (49.9%) of drugs were counterfeit | Inappropriate packaging, reduced amt of AI, reduced dissolution and stability, no AI, wrong ingredient, impurities |
| 2008/Tanzania (81) | Antimalarial drugs, tablets: SP, sulfamethoxy-pyrazinepyrimethamine, amodiaquine, quinine, artemisinin derivative (304) | HPLC and dissolution test with U.S. Pharmacopeia standards | 12.2% of drugs were substandard/counterfeit | Reduced dissolution and stability, reduced content of AI |
| 2007/Kenya (163) | Antimalarial drugs, Capsules, dry powder suspensions, injections, tablets: containing either artemisinin derivatives or dihydroartemisinin (24) | HPLC, UV | 38% of drugs, 66% of dry powder suspensions, and up to 23% of tablets were substandard/counterfeit | Reduced content of AI, increased content of AI |
| 2007/East Congo (172) | Antimalarial drugs, tablets, injections, and syrups: chloroquine, proguanil, quinine, SP (6 for each drug) | HPLC, UV, TLC | 43% of antimalarial medicines being sold were substandard/counterfeit; 33% of chloroquine, 25% of quinine, and 25% of SP were substandard/counterfeit | Inappropriate packaging and labeling, reduced dissolution and stability, reduced content of AI |
| 2006/Sudan (166) | Antimalarial drugs, tablets, syrup, suspension, injections: chloroquine; tablets, injections: quinine; injections: artemether; tablets: mefloquine | NR | Up to 30% of antimalarials were substandard/counterfeit; almost 84% of failures were due to reduced stability of the drug (quinine, chloroquine), 8% due to low AI (chloroquine), 8% due to low dissolution (chloroquine) | Inappropriate packaging and labeling, reduced dissolution and stability, reduced content of AI |
| 2006/Congo, Burundi, Angola (60) | Antimalarials, tablets: chloroquine, quinine, mefloquine (NR) | LC | Reduced amt of AI (quinine tablets) | Inappropriate packaging, reduced amt of AI, impurities due to poor storage conditions |
| 2006/Cambodia (40) | Antimalarials, tablets: quinine, chloroquine, artesunate, mefloquine, tetracycline, dihydroartemisinin, artemether (451) | Packaging analysis disintegration tests, HPLC, Mini-lab kits, TLC | 79% of antimicrobials were unregistered; overall, 27.1% samples were substandard/counterfeit (50/451 substandard and 72/451 counterfeit) | Unknown origins and unregistered products, inappropriate packaging, wrong AI, no AI |
| 2005/Yemen (177) | Antimalarials, tablets, syrups: chloroquine, SP (4 for each drug) | UV, HPLC, dissolution tests | Up to 20% of chloroquine and 80% of SP were substandard/counterfeit | Reduced dissolution and stability, reduced content of AI, increased content of AI |
| 2005/Tanzania (183) | Antimalarials, tablets: 11 brands of SP | HPLC, physical methods | 54.5% of brands failed the hardness, disintegration, or friability tests | Reduced dissolution and stability |
| 2005/Kenya (43) | Antimalarials, tablets and suspensions: SP and amodiaquine (116) | Spectrophotometric assay, HPLC, dissolution tests | 40.5% of antimicrobials (45.3% of SP and 33.0% of amodiaquine) were substandard/counterfeit | Reduced content of AI, reduced dissolution and stability |
| 2004/Southeast Asia, Myanmar (Burma), Lao PDR, Vietnam, Cambodia, Thailand (58) | Antimalarials, tablets: artemisinin derivatives, mefloquine (188) | Colorimetric testing (Fast Red dye) and packaging analysis, HPLC | 53% of artesunate and 9% of mefloquine samples were substandard/counterfeit; overall, 44% of drugs were substandard/counterfeit (4/232 substandard and 99/232 counterfeit) | Inappropriate packaging/labeling, no AI |
| 2004/Cameroon (57) | Antimalarials, tablets, capsules: chloroquine, quinine, SP (284) | Color reaction test, TLC | 38% of chloroquine, 74% of quinine, and 12% of sulfadoxine-pyrimethamine were substandard/counterfeit; overall, 39.4% of drugs were substandard/counterfeit | No AI, reduced content of AI, wrong AI, unknown ingredient(s) |
| 2004/Rwanda, Tanzania (38) | Antimalarials, tablets: quinine, SP (33) | Dissolution tests, HPLC | In total, 24% of the sampled formulations were substandard/counterfeit | Reduced dissolution and stability, reduced content of AI |
| 2004/Laos (28) | Antimalarials, tablets: chloroquine (300) | HPLC, TLC, UV, color reactions, mass uniformity analysis | Overall, 47% of chloroquine samples were substandard/counterfeit | Increased content of AI, wt variation outside pharmacopoeial limits |
| 2003/Uganda (176) | Antimalarials, tablets, injection: chloroquine (92) | HPLC | 44.5 % of chloroquine samples were substandard/counterfeit | Reduced content of AI, increased content of AI |
| 2003/Tanzania (165) | Antimalarials, tablets: amodiaquine, SP (33) | HPLC, TLC | 36% of samples were substandard | Reduced dissolution and stability, reduced content of AI |
| 2003/Gabon, Ghana, Kenya, Mali, Mozambique, Sudan, Zimbabwe (87) | Antimalarial drugs, tablets, syrup: chloroquine and SP (278) | HPLC, drug-specific assays and dissolution test | 23% of drugs were substandard/counterfeit | Reduced content of AI |
| 2002/Tanzania (34) | Antimalarials: chloroquine (2) | HPLC | Plain formulation of chloroquine phosphate was significantly more bioavailable than sugar-coated formulation | Reduced bioavailability |
| 2002/Tanzania (31) | Antimalarials, tablets: SP, chloroquine (22) | HPLC, accelerated stability test | Two SP and two chloroquine formulations had reduced dissolution | Reduced dissolution and stability, reduced content of AI |
| 2001/Southeast Asia, Cambodia, Laos, Myanmar (Burma), Thailand, Vietnam (9) | Antimalarials, tablets: artesunate (104) | Fast Red TR dye technique, physical characteristics of drugs and packages determined by independent observer | 38% of artesunate samples were counterfeit | Inappropriate packaging/labeling, wt variation outside pharmacopoeial limits, no AI, wrong AI |
| 2001/Sudan (185) | Antiparasitic agents, tablets: Praziquantel (34) | NR | Three brands did not meet the quality pharmacopoeial for impurities and formulation characteristics, and one brand was counterfeit and contained no AI | Wt variation outside pharmacopoeial limits, no AI, inappropriate packaging/labeling |
| 2001/Nigeria (7) | Antimalarials, tablets: SP; tablets: proguanil; tablets, injections, syrups: quinine; anthelmintic, tablets: mebendazole (581) | HPLC and dissolution test, British Pharmacopeia standards were used | More than 50% of drugs were substandard/counterfeit | No AI, reduced content of AI, increased content of AI |
| 2001/Cambodia (48) | Antimalarials, tablets: mefloquine artesunate (NR) | NR | Most mefloquine and half of the artesunate tablets were counterfeit | Inappropriate packaging/labeling |
| 1998/Uganda (175) | Antimalarials, Chloroquine (53 tablets and 49 injections) | Pharmacopoeial assays | Up to 30% of the tablet samples and 33% of injection samples were substandard/counterfeit | Reduced content of AI, increased content of AI |
| 1998/Laos (24) | Antimalarials, tablets: chloroquine (366) | Identity assay (TLC, UV, HPLC, color reactions), measurement of wt variation | 49% of chloroquine samples were substandard/counterfeit | No AI, reduced content of AI, increased content of AI, inappropriate packaging/labeling, wt variation outside pharmacopoeial limits |
| 1997/South Africa (209) | Anthelmintics, tablets: three rafoxanide products (3 brands) | The drugs were tested against a known susceptible strain of Haemonchus in sheep | One of the three commercial formulations (of highly reputable companies) was markedly substandard in terms of efficacy | Reduced efficacy, inappropriate packaging/labeling |
| 1997/Nigeria, Thailand (2) | Antimalarials, tablets, capsules, suspension, injection: chloroquine (81 Nigeria, 15 Thailand) | HPLC | Overall, 36.5% of drugs were substandard/counterfeit | No AI, reduced content of AI, increased content of AI |
| 1995/Tanzania (174) | Antimalarials: chloroquine tablets of nine different brands) (NR) | NR | Only 39% of sugar-coated chloroquine tablets passed the dissolution test | Reduced dissolution and stability |
| 1995/Amazonian region (63) | Antimalarials, tablets: primaquine (12) | NR | 50% of the samples were substandard/counterfeit; reduced and increased concn of AI | Reduced content of AI, increased content of AI |
| 1995/Nigeria (123) | Antimalarials, tablets and syrup formulations of chloroquine (40) | Approximately 8% of chloroquine tablets were substandard/counterfeit | Reduced content of AI |
a
Abbreviations: AI, active ingredient; HPLC, high-performance liquid chromatography; LC, liquid chromatography; NR, not reported; SP, sulfadoxine-pyrimethamine; TLC, thin-layer chromatography; UV, UV spectrophotometry.