Product quality evaluation of marketed veterinary Ivermectin formulations in Addis Abeba

Document Type : Original Article

Authors

1 Department of Pharmaceutical Technology, Institute of Health Sciences, Near East University, Turkiye & Ethiopian Agricultural Authority, Addis Ababa, Ethiopia

2 Department of Animal Science, Werabe University, Werabe, Ethiopia

3 University of Gondar, College of Veterinary Medicine and Animal Sciences, Gondar, Ethiopia

4 Department of Pharmaceutical Technology, Institute of Health Sciences, Near East University, Turkiye

5 Ethiopian Agricultural Authority, Addis Ababa, Ethiopia

6 Department of Pharmaceutical Technology, Altinbas University, Istanbul, Turkiye

Abstract

Objectives: To assess the prevalence of substandard products, a quality study based on the United States Pharmacopeia (USP) standards was conducted on the veterinary medicinal product ivermectin.
Methods: From September 2020 to January 2021, a cross-sectional quality analysis was carried out on 19 samples of pharmaceutical products. These samples were obtained from all veterinary retail outlets in Addis Ababa, Ethiopia. The analysis included organoleptic assessment for packaging-related information and physical appearance, as well as high-performance liquid chromatography (HPLC)-based physicochemical analysis for identity, assay, packaging uniformity, and HLB ratio. The procedures followed were in accordance with the USP recommendations. The quality analysis took place at the national veterinary drug quality test center.
Results: The quality analysis has revealed the presence of substandard products for uniformity of packaging (15.8%), API assay (15.8%), and filling to a volume (16.67%). However, both sampled products demonstrated the expected API, recommended physical appearance, and consistent packaging information. The prevalence ratio values for all H1B1a/(H1B1a+H1B1b) chemical species were greater than 0.95.
Conclusion: The findings from this study clearly indicate the alarming presence of substandard veterinary pharmaceutical products. This highlights the need for strengthening the regulatory surveillance system.

Keywords

Main Subjects

References

  1. Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA. Ivermectin: a potent new antiparasitic agent. Science. 1983;221(4613):823-8. doi:10.1126/science.6308762 PMid:6308762
  2. Crump A, Ōmura S. Ivermectin, 'wonder drug' from Japan: the human use perspective. Proc Jpn Acad Ser B Phys Biol Sci. 2011; 87(2):13-28 doi:10.2183/pjab.87.13 PMid:21321478 PMCid:PMC3043740
  3. González Canga A, Sahagún Prieto AM, Diez Liébana MJ, Fernández Martínez N, Sierra Vega M, García Vieitez JJ. The pharmacokinetics and interactions of ivermectin in humans--a mini-review. AAPS J. 2008;10(1):42-6 doi:10.1208/s12248-007-9000-9 PMid:18446504 PMCid:PMC2751445
  4. Low ZY, Yip AJW, Lal SK. Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication. Biochim Biophys Acta Mol Basis Dis. 2022; 1868 (2): 166294 doi:10.1016/j.bbadis.2021.166294 PMid:34687900 PMCid:PMC8526435
  5. Héctor C, Roberto H, Psaltis A, Veronica C. Study of the efficacy and safety of topical ivermectin+ iota-carrageenan in the prophylaxis against COVID-19 in health personnel. J biomed res clin investig. 2020; 2(1):1007 doi:10.31546/2633-8653.1007
  6. Campbell WC. Ivermectin and abamectin: Springer Science & Business Media; 2012.
  7. Steel JW. Pharmacokinetics and metabolism of avermectins in livestock. Vet Parasitol. 1993;48(1-4):45-57. doi:10.1016/0304-4017(93)90143-B PMid:8346648
  8. Puspitasari S, Farajallah A, Sulistiawati E, Muladno. Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia. Trop Life Sci Res. 2016;27(1):135-44 PMID: 27019686; PMCID: PMC4807958.
  9. Institute of Medicine (US) Forum on Emerging Infections. The Resistance Phenomenon in Microbes and Infectious Disease Vectors: Implications for Human Health and Strategies for Containment: Workshop Summary. Knobler SL, Lemon SM, Najafi M, Burroughs T, editors. Washington (DC): National Academies Press (US); 2003. PMID: 22649806
  10. Andersson DI, Hughes D. Microbiological effects of sublethal levels of antibiotics. Nat Rev Microbiol. 2014;12(7):465-78. doi:10.1038/nrmicro3270 PMid:24861036
  11. Nwokike J, Clark A, Nguyen PP. Medicines quality assurance to fight antimicrobial resistance. Bull World Health Organ. 2018; 96 (2):135-7 doi:10.2471/BLT.17.199562 PMid:29403117 PMCid:PMC5791778
  12. Jabbar A, Iqbal Z, Kerboeuf D, Muhammad G, Khan MN, Afaq M. Anthelmintic resistance: the state of play revisited. Life Sci. 2006; 79(26):2413-31. doi:10.1016/j.lfs.2006.08.010 PMid:16979192
  13. Wolstenholme AJ, Fairweather I, Prichard R, von Samson-Himmelstjerna G, Sangster NC. Drug resistance in veterinary helminths. Trends Parasitol. 2004;20(10):469-76. doi:10.1016/j.pt.2004.07.010 PMid:15363440
  14. Wolstenholme AJ, Evans CC, Jimenez PD, Moorhead AR. The emergence of macrocyclic lactone resistance in the canine heartworm, Dirofilaria immitis. Parasitology. 2015;142(10):1249-59 doi:10.1017/S003118201500061X PMid:26040450
  15. Nana-Djeunga HC, Bourguinat C, Pion SD, Bopda J, Kengne-Ouafo JA, Njiokou F, et al. Reproductive status of Onchocerca volvulus after ivermectin treatment in an ivermectin-naïve and a frequently treated population from Cameroon. PLoS Negl Trop Dis. 2014;8(4):e2824 doi:10.1371/journal.pntd.0002824 PMid:24762816 PMCid:PMC3998936
  16. 1 in 10 medical products in developing countries is substandard or falsified News release [Internet]. 2017; 2022(13 August). Available from: https://www.who.int/news/item/28-11-2017-1-in-10-medical-products-in-developing-countries-is-substandard-or-falsified#
  17. WHO CD. Guidelines for the development of measures to combat counterfeit drugs. WHO: Geneva, Switzerland. 1999.
  18. Addis Ababa City Administration Socioeconomic Data 2007. Available from: https://www.statsethiopia.gov.et/wp-content/uploads/2019/06/Addis_Ababa_Statistical-1.pdf.
  19. Schiavetti B, Wynendaele E, Melotte V, Van der Elst J, De Spiegeleer B, Ravinetto R. A simplified checklist for the visual inspection of finished pharmaceutical products: a way to empower frontline health workers in the fight against poor-quality medicines. J Pharm Policy Pract. 2020;13: 9. doi:10.1186/s40545-020-00211-9 PMid:32377348 PMCid:PMC7193355
  20. Ivermectin Monographs. In: In United States Pharmacopeia Convention Committee of Revision (Ed.) USP-NF, editor. USP 44 NF 34. USA2021.
  21. List of registered veterinary drug products in ethiopia. 2022.
  22. WHO Model List of Essential Medicines, World Health Organization. April 2015
  23. Bhorat QE, Bhorat AE. A qualitative analysis of seven ivermectin formulations in South Africa. S Afr Med J. 2021;111(4):288-290. doi:10.7196/SAMJ.2021.v111i4.15630 PMid:33944756
  24. Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products :Guidance for Industry. Draft Guidance for industry. 2015 [Last access date: 10.26.2022]
  25. Getahun M, Tefera B, Bacha B, Eticha T, Ashenef A. Quality of veterinary anthelmintic drugs marketed in Gondar Zones, North West Ethiopia; presence of poor-quality medicines. Heliyon. 2023; 9 (7): e18023. doi:10.1016/j.heliyon.2023.e18023 PMid:37483800 PMCid:PMC10362142
  26. Fijalek Z. Market Surveillance of Suspected Illegal Products MSSIP001: Slimming Dietary Supplements 2023; Summary Report.
  27. van der Schoot SC, Nuijen B, Huitema AD, Beijnen JH. Assessment of performance of manufacturing procedures in a unit for production of investigational anticancer agents, using a mixed effects analysis. Pharm Res. 2007;24(3):605-12 doi:10.1007/s11095-006-9179-y PMid:17245647 PMCid:PMC1915623
  28. Adediran OA, Uwalaka EC. Effectiveness Evaluation of Levamisole, Albendazole, Ivermectin, and Vernonia amygdalina in West African Dwarf Goats. J Parasitol Res. 2015;2015:706824. doi:10.1155/2015/706824 PMid:26579232 PMCid:PMC4633566
  29. Seifu A, Kebede E, Bacha B, Melaku A, Setegn T. Quality of albendazole tablets legally circulating in the pharmaceutical market of Addis Ababa, Ethiopia: physicochemical evaluation. BMC Pharmacol Toxicol. 2019;20(1):20. doi:10.1186/s40360-019-0299-5 PMid:31023365 PMCid:PMC6485143
  30. Tefera B, Bacha B, Belew S, Ravinetto R, Andualem T, Abegaz Z, et al. Study on identification, assay and organoleptic quality of veterinary medicines in Ethiopia. J Pharm Policy Pract. 2022; 15(1):17. doi:10.1186/s40545-022-00410-6 PMid:35241169 PMCid:PMC8892721
  31. A study on the public health and socioeconomic impact of substandard and falsified medical products. 2017.
  32. Geerts S, Gryseels B. Drug resistance in human helminths: current situation and lessons from livestock. Clin Microbiol Rev. 2000; 13 (2): 207-22 doi:10.1128/CMR.13.2.207 PMid:10755998 PMCid:PMC100151
  33. Shalaby HA. Anthelmintics Resistance; How to Overcome it? Iran J Parasitol. 2013;8(1):18-32. PMID: 23682256; PMCID: PMC3655236
  34. Bersissa K, Abebe W. Efficacy of albendazole and tetramisole anthelmintics against Haemonchus contortus in experimentally infected lambs. 2006.
  35. Eguale T, Chaka H, Gizaw D. Efficacy of albendazole against nematode parasites isolated from a goat farm in Ethiopia: relationship between dose and efficacy in goats. Trop Anim Health Prod. 2009;41(7):1267-73. doi:10.1007/s11250-009-9311-1 PMid:19194779
  36. Roos MH. Drug resistance in the sheep nematode parasite Haemonchus contortus, mechanisms and clinical perspectives. InAntimicrobial Drug Resistance: Clinical and Epidemiological Aspects 2009 (pp. 1127-1132). Totowa, NJ: Humana Press. doi:10.1007/978-1-60327-595-8_32
International Archives of Health Sciences
Volume 10, Issue 4
December 2023
Pages 156-163

Files

History

  • Receive Date: 14 August 2023
  • Revise Date: 23 October 2023
  • Accept Date: 29 October 2023

Share

How to cite

Statistics