Quality Assessment of Selected Essential Antimicrobial Drugs from Drug Retail Outlets of Selected Cities in Eastern Ethiopia

Hailu Anjulo Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia;
Ethiopian Food and Drug Authority, Addis Ababa, Ethiopia;

Search for other papers by Hailu Anjulo in
Current site
Google Scholar
PubMed
Close
,
Worku Birhane Department of Pharmacy, College of Health Science, Debremarkos University, Debremarkos, Ethiopia;

Search for other papers by Worku Birhane in
Current site
Google Scholar
PubMed
Close
,
Ariaya Hymete Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia;

Search for other papers by Ariaya Hymete in
Current site
Google Scholar
PubMed
Close
, and
Ayenew Ashenef Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia;
Center for Innovative Drug Development and Therapeutic Trials for Africa, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia

Search for other papers by Ayenew Ashenef in
Current site
Google Scholar
PubMed
Close
Restricted access

ABSTRACT.

The prevalence of substandard and falsified (SF) antimicrobial drugs is increasing around the globe. This poses a great concern for the healthcare system. The consumption of SF antimicrobial drugs has the potential to result in treatment failure, emergence and development of antimicrobial resistance, and ultimately a rise in mortality rate. The objective of this study was to assess the quality of four commonly used antimicrobials marketed in the cities of Dire Dawa and Jijiga and the town of Togo-Wuchale, which have high potential for illegal drug trade activities in Ethiopia because they are located near the border with Somalia. A total of 54 brands/samples of amoxicillin, amoxicillin/clavulanic acid, ciprofloxacin, and norfloxacin formulations were collected covertly from 43 facilities using a convenience sampling strategy from March 16 to March 29, 2022. The samples were first screened using Global Pharma Health Fund (GPHF)-Minilab protocols and then analyzed using U.S. Pharmacopoeial and British Pharmacopoeia official methods. The quality evaluation detected no falsified product; however, it showed that 14.3% of the samples failed the GPHF-Minilab screening test semiquantitatively. Overall, 22.2% of the products analyzed did not meet any of pharmacopoeial specifications assessed: 13%, 12.2%, and 11.1% of the products failed in assay, dissolution, and weight variation, respectively. Additionally, 56.3% of amoxicillin samples, 60% of amoxicillin/clavulanate, 20% of ciprofloxacin, and 54.5% of norfloxacin samples were found to be pharmaceutically nonequivalent with their respective comparator products regarding dissolution profiles. The study showed the presence of substandard antimicrobial medicines in the eastern Ethiopian market.

Author Notes

Financial support: This study was funded by Addis Ababa University.

Authors’ addresses: Hailu Anjulo, Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia, and Ethiopian Food and Drug Authority, Addis Ababa, Ethiopia, Email: hailuanjulo@gmail.com. Worku Birhane, Department of Pharmacy, College of Health Science, Debremarkos University, Debremarkos, Ethiopia, Email: workub36@gmail.com. Ariaya Hymete and Ayenew Ashenef, Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia, E-mails: ariaya.hymete@aau.edu.et and ayenew.ashenef@aau.edu.et.

Address correspondence to Ayenew Ashenef, Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia. E-mail: ayenew.ashenef@aau.edu.et
  • 1.

    Wirtz VJ et al., 2017. Essential medicines for universal health coverage. Lancet Publishing Group Lancet. 389: 403476.

  • 2.

    Ozawa S , Shankar R , Leopold C , Orubu S , 2019. Access to medicines through health systems in low- and middle-income countries. Health Policy Plan 34 (Suppl 3): iii1iii3.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Global Burden of Disease 2015 Sustainable Development Goals Collaborators , 2016. Measuring the health-related sustainable development goals in 188 countries: a baseline analysis from the Global Burden of Disease Study 2015. The Lancet 388: 18131850.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    World Health Organization , 2017. WHO Global Surveillance and Monitoring System for Substandard and Falsified Medical Products. Geneva, Switzerland: WHO.

  • 5.

    Dadgostar P , 2019. Antimicrobial resistance: implications and costs. Infect Drug Resist 12: 39033910.

  • 6.

    Mendelson M , Matsoso MP , 2015. The World Health Organization Global Action Plan for antimicrobial resistance. S Afr Med J 105: 325.

  • 7.

    Zabala GA , Bellingham K , Vidhamaly V , Boupha P , Boutsamay K , Newton PN , Caillet C , 2022. Substandard and falsified antibiotics: neglected drivers of antimicrobial resistance? BMJ Glob Health 7: e008587.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    World Health Organization , 2017. A Study on the Public Health and Socioeconomic Impact of Substandard and Falsified Medical Products. Geneva, Switzerland: WHO.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Ozawa S , Evans DR , Bessias S , Haynie DG , Yemeke TT , Laing SK , Herrington JE , 2018. Prevalence and estimated economic burden of substandard and falsified medicines in low- and middle-income countries. JAMA Netw Open 1: e181662.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Pharmaceutical Security Institute , 2019. Incident Trends. Available at: https://www.psi-inc.org/incident-trends. Accessed July 1, 2019.

    • PubMed
    • Export Citation
  • 11.

    Kelesidis T , Falagas ME , 2015. Substandard/counterfeit antimicrobial drugs. Clin Microbiol Rev 28: 443464.

  • 12.

    Schäfermann S et al., 2020. Substandard and falsified antibiotics and medicines against noncommunicable diseases in western Cameroon and northeastern Democratic Republic of Congo. Am J Trop Med Hyg 103: 894908.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Rentz ED et al., 2008. Outbreak of acute renal failure in Panama in 2006: a case–control study. Bull World Health Organ 86: 749756.

  • 14.

    U.S. Promoting the Quality of Medicines Program , 2019. Medicines Quality Database and Poor-Quality Medicines ALERT. Available at: https://apps.usp.org/app/worldwide/medQualityDatabase/terms.html. Accessed July 1, 2019.

    • PubMed
    • Export Citation
  • 15.

    Hajjou M et al., 2015. Monitoring the quality of medicines: results from Africa, Asia, and South America. Am J Trop Med Hyg 92: 6874.

  • 16.

    Sweileh WM , 2021. Substandard and falsified medical products: bibliometric analysis and mapping of scientific research. Global Health 17: 113.

  • 17.

    World Health Organization , 2015. Guidelines on the Conduct of Surveys of the Quality of Medicines (WHO-TRS No. 996, 2016, Annex 7). Geneva, Switzerland: WHO.

  • 18.

    Ministry of Health/Ethiopian Food and Drug Authority , 2020. Ethiopian Essential Medicines List. 6th ed. Addis Ababa, Ethiopia: EFDA.

  • 19.

    Gutema G , Ali S , Suleman S , 2021. Trends of community-based systemic antibiotic consumption: comparative analyses of data from Ethiopia and Norway calls for public health policy actions. PLoS One 16: e0251400.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Kelesidis T , Kelesidis I , Rafailidis PI , Falagas ME , 2007. Counterfeit or substandard antimicrobial drugs: a review of the scientific evidence. J Antimicrob Chemother 60: 214236.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Global Pharm Health Fund , 2020. GPHF-Minilab: A Concise Quality Control Guide on Essential Drugs and other Medicines Manual. Giessen, Germany: GPHF.

  • 22.

    The United States Pharmacopoeia National Formulary , 2021. USP 44-NF 39. Rockville, MD: U.S. Pharmacopoeia Convention.

    • PubMed
    • Export Citation
  • 23.

    The British Pharmacopoeia , 2021. The British Pharmacopoeia. London, United Kingdom: TSO.

  • 24.

    Office of Training and Communications Division of Communications Management. The Drug Information Branch, U.S. Food and Drug Administration , 1997. Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Formulations. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/dissolution-testing-immediate-release-solid-oral-dosage-forms. Accessed September 26, 2022.

    • PubMed
    • Export Citation
  • 25.

    Zhang Y , Huo M , Zhou J , Zou A , Li W , Yao C , Xie S , 2010. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J 12: 263271.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Allen LV , Popovich NG , Ansel HC , 2009. Pharmaceutical Dosage Forms and Drugs Delivery System. 9th ed. Philadelphia, PA: Walters Kluwer/Lipincott Williams & Wilkins.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    U.S. Food and Drug Administration , 2015. Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules Guidance for Industry. Rockville, MD: Center for Drug Evaluation and Research.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Muselík J , Komersová A , Kubová K , Matzick K , Skalická B , 2021. A critical overview of FDA and EMA statistical methods to compare in vitro drug dissolution profiles of pharmaceutical products. Pharmaceutics 13: 1703.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Usta DY , Incecayir T , 2022. Modeling of in vitro dissolution profiles of carvedilol immediate-release tablets in different dissolution media. AAPS PharmSciTech 23: 201.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    World Health Organization, Expert Committee on Specifications for Pharmaceutical Preparations , 2015. Guidance on the Selection of Comparator Pharmaceutical Products for Equivalence Assessment of Interchangeable Multisource (Generic) Products. WHO TRS 992 Annex 8. Geneva, Switzerland: WHO.

    • PubMed
    • Export Citation
  • 31.

    Rojas-Cortés R , 2020. Substandard, falsified and unregistered medicines in Latin America, 2017–2018. Rev Panam Salud Publica 44. doi: 10.26633/RPSP.2020.125.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Sutherland A , Waldek S , 2015. It is time to review how unlicensed medicines are used. Eur J Clin Pharmacol 71: 10291035.

  • 33.

    Kahsay G , Debella A , Asres K. , 2007. Comparative in vitro quality evaluation of ciprofloxacin tablets from drug retail outlets in Addis Ababa, Ethiopia. Ethiopian Pharm J 25: 18.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Waqas MK , Ali R , Usman M , Shahid MN , Rasul A , Khan BA , Murtaza G , 2020. In vitro comparative dissolution assessment of different brands of co-amoxiclav tablets in Pakistan. Dissolut Technol 27: 18.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    World Health Organizatoin , 2011. Survey of the Quality of Selected Antimalarial Medicines Circulating in Six Countries of Sub-Saharan Africa. Available at: https://www.afro.who.int/publications/survey-quality-selected-antimalarial-medicines-circulating-six-countries-sub-saharan. Accessed June 1, 2021.

    • PubMed
    • Export Citation
  • 36.

    Kassaye L , Genete G , 2013. Evaluation and comparison of in-vitro dissolution profiles for different brands of amoxicillin capsules. Afr Health Sci 13: 369375.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Hailu GS , Gutema GB , Hishe HZ , Ali YS , Asfaw AA , 2013. Comparative in vitro bioequivalence evaluation of different brands of amoxicillin capsules marketed in Tigray, Ethiopia. Int J Pharm Sci Nanotechnol 6: 19661971.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Al-Tabakha M , Fahelelbom K , Obaid DEE , Sayed S , 2017. Quality attributes and in vitro bioequivalence of different brands of amoxicillin trihydrate tablets. Pharmaceutics 9: 18.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Hambisa S , Belew S , Suleman S , 2019. In vitro comparative quality assessment of different brands of norfloxacin tablets available in Jimma, Southwest Ethiopia. Drug Des Devel Ther 13: 12411249.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Hintsa G , Murad F , 2018. Comparative in-vitro bioequivalence analysis of some brands of ciprofloxacin HCl tablets marketed in Ethiopia. Int J Res Pharm Sci 8: 3338.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Jain D , Pathak D , Pathak K , 2009. Pharmaceutical product development technologies based on the biopharmaceutical classification system. Die Pharmazie Int J Pharm Sci 64: 483490.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Banakar U , 2022. Pharmaceutical Dissolution Testing, Bioavailability, and Bioequivalence. Hoboken, NJ: John Wiley & Sons.

Past two years Past Year Past 30 Days
Abstract Views 234 234 64
Full Text Views 28 28 1
PDF Downloads 30 30 2
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save