Evaluation of drug permeability methods recommended by health authorities

The oral route is the most preferred route for drug administration because of patient compliance. Following oral administration, a drug has to cross several biological barriers before reaching the systemic circulation by transcellular or paracellular transports. Oral drug absorption and bioavailability are influenced by the physicochemical, formulation and physiological variables. Oral absorption of drugs is controlled by dissolution from the dosage form, and permeability across the gastrointestinal mem-brane. Rate limiting step in absorption is the permeability for compounds with low permeability, and dissolution for compounds with low solubility. According to Food and Drug Administration (FDA) Biopharmaceutics Classification System (BCS)-based biowaiver guidance and European Medicines Agency (EMA) Guideline on the Investigation of Bioequivalence, permeability class of a drug substance can be determined using different methods. The aim of this study was to evaluate the methods in detail recommended by FDA and EMA for determination of permeability of drugs. We surveyed the literature as to the pros and cons of the methods recommended by the health authorities for assessment of permeability. In general, a single method is sufficient for determination of permeability. When a single method fails to demonstrate a permeability classification, two different methods may be used

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1. Hirota J, Shimizu S. Routes of Administration in The Laboratory Mouse. Second Edition. Academic Press, USA, 2012;709-725.

2. Kayaalp SO. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji (c. 1). Nüve Matbaası, Ankara, 1981.

3. Hannan PA, Khan JA, Khan A, et al. Oral dispersible system: A new approach in drug delivery system. Indian J Pharm Sci. 2016;78:2-7.

4. Löbenberg R, Amidon GL, Ferraz HG, et al. Mechanism of gastrointestinal drug absorption and application in therapeutic drug delivery. Therapeutic Delivery Methods: A Concise Overview of Emerging Areas. Beom-Jin Lee Future Science Ltd Unitec House, 2 Albert Place, London, 2013;8-22.

5. Horter D, Dressman JB. Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev. 2001;46:75-87.

6. Hillyer JF, Albrecht RM. Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. J Pharm Sci. 2001; 90:1927-36.

7. Lin L, Wong H. Predicting oral drug absorption: Mini review on physiologically based pharmacokinetic models. Pharmaceutics. 2017;9:41.

8. Amidon GL, Lennernas H, Shah VP, et al. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413-20.

9. U.S. Department of Health and Human Services Food and Drug Administration. Guidance for Industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System Guidance for Industry. https://www.fda.gov/downloads/Drugs/Guidances/ucm070246.pdf access date 22.07.2019

10. European Medicines Agency. Guideline on The Investigation of Bioequivalence. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf access date 25.07.2019

11. Penner N, Klunk LJ, Prakash C. Human radiolabeled mass balance studies: Objectives, utilities and limitations. Biopharm. Drug Dispos. 2009;30:185-203.

12. Lappin G, Rowland M, Garner RC. The use of isotopes in the determination of absolute bioavailability of drugs in humans. Expert Opin. Drug Metab Toxicol. 2006;2:419-27.

13. Ewe K, Wanitscke R, Staritz M. Intestinal Permeability Studies in Humans. In: TZ Csáky, eds, Pharmacology of Intestinal Permeation II. New York: Springer-Verlag. 1984;535-71.

14. Dahlgren D, Roos C, Sjogren E, et al. Direct In vivo human intestinal permeability (Peff) determined with different clinical perfusion and intubation methods. J Pharm Sci. 2015;104:2702–26.

15. ICH guideline M9 on Biopharmaceutics Classification System Based Biowaivers. https://www.ema.europa.eu/en/ich-m9-biopharmaceutics-classification-system-based-biowaivers access date 10.12.2019

16. Lentz KA, Hayashi J, Lucisano LJ, Polli JE. Development of a more rapid, reduced serum culture system for Caco-2 monolayers and application to the biopharmaceutics classification system. Int J Pharm. 2000; 200:41-51.

17. Bock U, Flötotto T, Haltner E. Validation of cell culture models for the intestine and the blood-brain barrier and comparison of drug permeation. LTEX. 2004;21:57-64.

18. Volpe DA, Faustino PJ, Ciavarella AB, et al. Classification of drug permeability with a Caco-2 cell monolayer assay. Clin Res Regul Aff. 2007;24:39-47.

19. Volpe DA. Application of method suitability for drug permeability classification. AAPS J. 2010;12:670-8.