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In Vitro Dissolution of Generic Immediate-Release Solid Oral Dosage Forms Containing BCS Class I Drugs: Comparative Assessment of Metronidazole, Zidovudine, and Amoxicillin Versus Relevant Comparator Pharmaceutical Products in South Africa and India

  • Research Article
  • Theme: Recent Advances in Dissolution and In Vitro Release of Dosage Forms
  • Published:
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Abstract

Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

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References

  1. Newton NP. Impact of poor-quality medicines in the ‘developing’ world. Trends Pharmacol Sci. 2010;31(3):99–101.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Nsimba SED. Problems associated with substandard and counterfeit drugs in developing countries: a review article on global implications of counterfeit drugs in the era of anti-retroviral (ARVs) drugs in a free market economy. East Afr J Public Health. 2008;5(3):205–10.

    PubMed  Google Scholar 

  3. Ministry of Health and family Welfare-India. Reward Scheme for whistle blowers in the fight against the menace of spurious or fake drugs, cosmetics and medical devices. 2010; p.1–9. http://www.cdsco.nic.in/writereaddata/whistle%20Blowe%20(3).pdf.

  4. National Drug Policy for South Africa. http://www.doh.gov.za/docs/policy/drugsjan1996.pdf. 1996. Accessed 10 Feb 2011.

  5. FDA, CDER. Guidance for industry: Dissolution testing of immediate release solid oral dosage forms. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidancesucm070237.pdf. 1997. Accessed 12 Mar 2012.

  6. Löbenberg R, Chacra NB, Stippler ES, Shah VP, Stefano AJD, Hauck WW, et al. Towards global standards for comparator pharmaceutical product: case studies of amoxicillin, metronidazole, and zidovudine in the Americas. AAPS J. 2012;14(3):462–71.

    Article  PubMed Central  PubMed  Google Scholar 

  7. WHO. Fortieth report: annex 7: multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability. Geneva: WHO; 2006. p. 347–90.

    Google Scholar 

  8. Löbenberg R, Amidon GL. Modern bioavailability, bioequivalence and biopharmaceutics classification system. New scientific approaches to international regulatory standards. Eur J Pharm Biopharm. 2000;50(1):3–12.

    Article  PubMed  Google Scholar 

  9. Gupta E, Barends DM, Yamashita E, Lentz KA, Harmsze AM, Shah VP, et al. Review of global regulations concerning biowaivers for immediate release solid oral dosage forms. Eur J Pharm Sci. 2006;29(3–4):315–24.

    Article  CAS  PubMed  Google Scholar 

  10. FDA, CDER. Guidance for industry. Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms containing certain active moieties/active ingredients based on a biopharmaceutics classification system. http://www.fda.gov/ohrms/dockets/98fr/990121gd.pdf. 1999. Accessed 28 Dec 2013.

  11. WHO, General notes on biopharmaceutics classification system (BCS)—based biowaiver applications. http://apps.who.int/prequal/info_applicants/BE/BW_general_2012October.pdf. October 2012. Accessed 28 Dec 2013.

  12. Verbeeck RK, Musuamba FT. The revised 2010 EMA guideline for the investigation of bioequivalence for immediate release oral formulations with systemic action. J Pharm Pharm Sci. 2012;15(3):376–88.

    CAS  PubMed  Google Scholar 

  13. FDA, CDER. Guidance for industry. Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. August 2000. http://www.fda.gov/downloads/Drugs/…/Guidances/ucm070246.pdf Accessed 18 May 2011.

  14. EMEA, CHMP, CPMP/EWP/QWP/1401/98 Rev. 1/Corr, Guideline on the investigation of bioequivalence. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf. Accessed 28 Dec 2013.

  15. United States Pharmacopoeia, Buffer solutions. http://www.uspbpep.com/usp29/v29240/usp29nf24s0_ris1s119.html. Accessed 18 May 2011.

  16. USP-NF. Validation of compendial procedures <1225>, https://hmc.usp.org/sites/default/files/documents/HMC/GCs-Pdfs/c1225%20USP36.pdf . 2007. p.1-10.17. Accessed 18 May 2011.

  17. USP. Dissolution <711>. US Pharmacopeial Convention, Rockville, MD. http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/2011-02-25711DISSOLUTION.pdf. 2011, p. 1-8. Accessed 18 May 2011.

  18. FDA. Orange book: approved drug products with therapeutic equivalence evaluations. http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm . 2012. Accessed Jan 2012.

  19. FDA. Orange book: approved drug products with therapeutic equivalence evaluations. http://www.accessdata.fda.gov/scripts/cder/ob/docs/temptn.cfm. 2011. Accessed 18 May 2011.

  20. FDA. Orange book: approved drug products with therapeutic equivalence evaluations. http://www.accessdata.fda.gov/scripts/cder/ob/docs/tempai.cfm. 2011. Accessed 18 May 2011.

  21. WHO. Model list of essential medicines. 18th list http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf. 2013. Accessed 29 Dec 2013.

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Acknowledgments

This study was supported by the Biopharmaceutics Research Institute (BRI), Rhodes University, South Africa, and Dr. Prabhakar Kore Basic Sciences Research Center (BSRC), KLE University, India.

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Authors and Affiliations

  1. Basic Science Research Center, KLE University, Belgaum, Karnataka, 590010, India

    Nallagundla H. S. Reddy & Srinivas Patnala

  2. Faculty of Pharmacy, University of Alberta, Edmonton, T6G 2R3, Canada

    Raimar Löbenberg

  3. Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Grahamstown, 6139, South Africa

    Isadore Kanfer

Authors
  1. Nallagundla H. S. Reddy
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  2. Srinivas Patnala
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  3. Raimar Löbenberg
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  4. Isadore Kanfer
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Correspondence to Isadore Kanfer.

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Guest Editor: Susan D’Souza

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Reddy, N.H.S., Patnala, S., Löbenberg, R. et al. In Vitro Dissolution of Generic Immediate-Release Solid Oral Dosage Forms Containing BCS Class I Drugs: Comparative Assessment of Metronidazole, Zidovudine, and Amoxicillin Versus Relevant Comparator Pharmaceutical Products in South Africa and India. AAPS PharmSciTech 15, 1076–1086 (2014). https://doi.org/10.1208/s12249-014-0135-6

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