POST MARKETING SURVEILLANCE OF ACTIVE PHARMACEUTICAL INGREDIENTS (API) IN ANTIMALARIAL DRUGS USED IN MALAWI

ABSTRACT The use of poor quality antimalarials causes low bioavailability of the active pharmaceutical ingredients (APIs) to the drug targets resulting in treatment ineffectiveness or failure and parasite resistance over a short period of drug usage. Resistance has rendered the hitherto cheap and effective drugs like chloroquine and sulphadoxine/pyrimethamine ineffective, resulting in their replacement with the more expensive artemisinin-based combination therapy (ACT) for malaria treatment. The high cost of the ACTs has made them attractive to counterfeiters leading to the proliferation of poor quality antimalarials on the drug markets. One hundred and twelve (112) samples of antimalarial drugs were purchased from licensed and unlicensed markets in all parts of Malawi. Samples were subjected to visual inspection of dosage form and packaging, registration verification with the Pharmacy, Medicines and Poisons Board of Malawi, basic tests and semi-quantitative thin layer chromatography (SQ-TLC) and HPLC tests to quantify the APIs in the samples and compare with pharmacopoeial specifications and the manufacturers’ claims. The results showed an 85 % registration status with all samples purported to be imported and 100% compliance with visual inspection requirements and basic tests confirming the presence of requisite APIs. The results of the SQ-TLC showed that 4.88% of artemether/lumefantrine (Atm/Lum) FDC samples were compliant with pharmacopoeial specifications, 2.44% were borderline compliant and a further 92.68% were non-compliant (48.15% of Atm component was overdose and 51.85% under dose; 57.14% of Lum component was overdose and the remaining 42.86% under dose). The HPLC results confirmed this result with 4.88% found to be compliant and 95.12% non-compliant (48.15% overdose and 51.85% under dose for Atm component; 50% overdose and 50% under dose for Lum component). SQ-TLC tests on artesunate/sulphadoxine/pyrimethamine (Ats/SP) samples showed that 77.78% were non- compliant all of which were under dose, while 22.22% were borderline compliant. However, the HPLC results showed a compliant percentage of 11.10% and 88.90% non-compliance (under dose). The dihydroartemisinin/piperaquine phosphate (Dha/Pp) samples recorded SQ-TLC percentage of 42.86% being compliant, 14.29% borderline compliant and 42.86% non-compliant with all the non-compliant quantities of the components found under dose. With HPLC, they were found to be 28.57% compliant, 7.14% borderline compliant and 64.29% non-compliant (under dosed components). Dihydroartemisinin/sulphadoxine/pyrimethamine (Dha/SP) samples were found to be 100% non-compliant for both SQ-TLC and HPLC tests. The quantities of the APIs in the non-compliant Dha/S/P samples fell within the range of 51% and 84%. Samples containing sulphadoxine/pyrimethamine (SP) were found to be 4.35% compliant, 8.70% borderline compliant and 86.95% non-compliant using SQ-TLC method (25.00% of the noncompliant pyrimethamine component overdose, 75.00% under dose and 100.00% of sulphadoxine under dose). With HPLC, half (50.00%) of the samples that were borderline compliant were found to be non-compliant with the remaining half being compliant giving rise to the following results: 8.70% and 91.30% compliant and non-compliant respectively with all noncompliant sulphadoxine and 72.73% of pyrimethamine being under dose and 27.27% of the quantities of pyrimethamine being overdose. None of the quinine samples were compliant with SQ-TLC (28.57% borderline compliant, 71.43% non-compliant and overdose). HPLC analysis found 30.77%, 15.38% and 53.85% to be compliant, borderline compliant and non-compliant (85.71% overdosed) respectively. Generally, 85.71% failure rate was found arising from Atm/Lum (95.12%), Dha/P (64.30%), Dha/SP (100.00%), SP (91.30%), Ats/SP (88.90%) and quinine (53.80%) failure rates indicating wide spread circulation of poor quality antimalarial drugs in Malawi.