Quality of Essential Medicines from Different Sources in Enugu and Anambra, Nigeria

Abstract

This study investigated the quality of 13 essential medicines in the states of Enugu and Anambra, Nigeria. A total of 260 samples were purchased from licensed pharmaceutical manufacturers and wholesalers and from vendors in pharmaceutical markets with unclear licensing status. Samples were analyzed for identity, content, and dissolution according to the United States Pharmacopeia (USP) 42 monographs. Forty-five samples of this study could be examined for authenticity with the Mobile Authentication Service scheme of the Nigerian National Agency for Food and Drug Administration and Control. Out of all samples, 25.4% did not comply with the USP 42 specifications. Strikingly, 21 out of 22 dexamethasone tablet samples (95%) were out of specification (OOS). Nine out of 19 glibenclamide samples (47%) failed dissolution testing, and 7 out of 17 cotrimoxazole samples (41%) failed assay testing. Medicines against noncommunicable diseases showed a slightly higher percentage of OOS samples than anti-infectives (21.2% versus 17.6%). The rates of OOS samples were similar in medicines stated to be produced in Nigeria, India, and China but were very different between individual manufacturers from each of these countries of origin. Therefore, prequalification of products, manufacturers, and suppliers are very important for quality assurance in medicine procurement. Unexpectedly, the total proportions of OOS samples were similar from licensed vendors (25.2%) and from markets (25.5%). Four samples (1.5%), all collected in markets, were clearly falsified and did not contain the declared active pharmaceutical ingredients. The proportion of falsified medicines was found to be lower than frequently reported in the media for Nigeria.

Figure 1.

Number of samples stated to be manufactured in different countries and results of their compendial quality testing. See the legend for Figure 5 for definitions of quality categories. The four discovered falsified medicines (containing no active pharmaceutical ingredient [API] or a wrong API) were stated to be manufactured in Nigeria, but this statement might be incorrect.

Figure 2.

Four falsified medicines discovered in this study. Products A, B, and C contained different kinds of tablets, with different embossings and thicknesses, in the same container. None of these contained any active pharmaceutical ingredient. Product D contained paracetamol (27 mg per tablet) instead of the labeled ingredients sulfamethoxazole and trimethoprim.

Figure 3.

Content and dissolution of the active pharmaceutical ingredient (API) determined for each sample, expressed as a percentage of the stated API amount. (A) Content of the API. (B) Dissolution of the API. The specification limits of the United States Pharmacopeia (USP) (Q values in case of dissolution) are depicted. ^aFor this ciprofloxacin sample, individual tablets showed a dissolution of less than Q minus 15%. Thereby, this sample deviates from USP specifications, even though its mean dissolution is above the pharmacopeial Q value of 80%. ^bThis metformin sample was formulated as an extended-release tablet. Therefore, dissolution testing was carried out and evaluated according to the USP monograph for metformin extended-release tablets (see Supplemental Table S1). Dissolution testing was not carried out for four samples that already showed in assay analysis contents of chloroquine, metronidazole, or trimethoprim lower than Q minus 25% (see text). Their API contents are depicted in Figure 3B with underlined symbols.

Figure 4.

Results of compendial analysis for different therapeutic groups, for different sources of medicines, and for medicines with verifiable and nonverifiable National Agency for Food and Drug Administration and Control (NAFDAC) registration numbers (see text). Dexamethasone can be used in the treatment of both COVID-19 and noncommunicable diseases and was therefore excluded from the comparison of anti-infective medicines with medicines against noncommunicable diseases. See the legend for Figure 5 for definitions of quality categories.

Figure 5.

Results of compendial analysis for the investigated active pharmaceutical ingredients (APIs). ^aOnly 15 of 22 fluconazole samples were tested for dissolution, since 7 samples were collected as capsules and no dissolution testing method for fluconazole capsules is specified in the United States Pharmacopeia (USP). ^bOnly 25 of 26 ciprofloxacin samples were tested for dissolution, because not enough dosage units were available for one of the samples. ^cFor assay values, the following five categories were used^,,: 1) containing no or wrong APIs (i.e., “falsified”); 2) containing less than 50% of the declared API amount, without evidence that their low content was due to API degradation (i.e., “probably falsified”); 3) other samples deviating by more than 20% from the declared API amount (i.e., “extreme deviation”); 4) deviations from USP assay specifications by not more than 20% of the declared API amount (i.e., “moderate deviation”); 5) in specification. ^dFor dissolution values, average dissolution values lower than Q minus 25% were considered “extreme deviations”; dissolution values below USP specifications but not lower than Q minus 25% on average were considered “moderate deviations”. The categories “falsified” and “probably falsified” were not used, as these categories were based on assay results alone.

Figure 6.

Results of compendial analysis for different stated manufacturers from Nigeria. See the legend for Figure 5 for definitions of quality categories. ^aThe names of the four stated manufacturers of falsified medicines could not be found by an internet search nor in Nigeria’s Registered Drug Product Database. Apparently, these four manufacturers do not exist.

Figure 7.

(A) SMS verification of a Mobile Authentication Service (MAS) PIN code resulting in a correct but incomplete response; see text for National Agency for Food and Drug Administration and Control (NAFDAC) requirements for a complete response. (B) SMS verification of a MAS PIN code resulting in an incorrect response (i.e., a wrong product name). (C) Summary of all results of MAS PIN code testing.