Advertisement

AAPS PharmSciTech

, Volume 19, Issue 7, pp 2885–2897 | Cite as

Physiological Considerations and In Vitro Strategies for Evaluating the Influence of Food on Drug Release from Extended-Release Formulations

  • Mirko Koziolek
  • Edmund Kostewicz
  • Maria Vertzoni
Review Article Theme: Advancements in Dissolution Testing of Oral and Non-Oral Formulations
  • 127 Downloads
Part of the following topical collections:
  1. Theme: Advancements in Dissolution Testing of Oral and Non-Oral Formulations

Abstract

Food effects on oral drug bioavailability are a consequence of the complex interplay between drug, formulation and human gastrointestinal (GI) physiology. Accordingly, the prediction of the direction and the extent of food effects is often difficult. With respect to novel formulations, biorelevant in vitro methods can be extremely powerful tools to simulate the effect of food-induced changes on the physiological GI conditions on drug release and absorption. However, the selection of suitable in vitro methods should be based on a thorough understanding not only of human GI physiology but also of the drug and formulation properties. This review focuses on in vitro methods that can be applied to evaluate the effect of food intake on drug release from extended release (ER) products during preclinical formulation development. With the aid of different examples, it will be demonstrated that the combined and targeted use of various biorelevant in vitro methods can be extremely useful for understanding drug release from ER products in the fed state and to be able to forecast formulation-associated risks such as dose dumping in early stages of formulation development.

KEY WORDS

food effect oral bioavailability biorelevant dissolution testing extended release dosage forms in vitro 

References

  1. 1.
    Fleisher D, Li C, Zhou Y, Pao L-H, Karim A. Drug, meal and formulation interactions influencing drug absorption after oral administration: clinical implications. Clin Pharmacokinet. 1999;36(3):233–54.CrossRefGoogle Scholar
  2. 2.
    Koziolek M, Grimm M, Schneider F, Jedamzik P, Sager M, Kühn JP, et al. Navigating the human gastrointestinal tract for oral drug delivery: uncharted waters and new frontiers. Adv Drug Deliv Rev. 2016;101:75–88.CrossRefGoogle Scholar
  3. 3.
    Schug BS, Brendel E, Wolf D, Wonnemann M, Wargenau M, Blume HH. Formulation-dependent food effects demonstrated for nifedipine modified-release preparations marketed in the European Union. Eur J Pharm Sci. 2002;15(3):279–85.CrossRefGoogle Scholar
  4. 4.
    Hendeles L, Weinberger M, Milavetz G, Hill M, Vaughan L. Food-induced “dose-dumping” from a once-a-day theophylline product as a cause of theophylline toxicity. Chest J. 1985;87(6):758–65.CrossRefGoogle Scholar
  5. 5.
    Koziolek M, Garbacz G, Neumann M, Weitschies W. Simulating the postprandial stomach: physiological considerations for dissolution and release testing. Mol Pharm. 2013;10(5):1610–22.CrossRefGoogle Scholar
  6. 6.
    Varum FJ, Hatton GB, Basit AW. Food, physiology and drug delivery. Int J Pharm. 2013;457(2):446–60.CrossRefGoogle Scholar
  7. 7.
    Weitschies W, Blume H, Mönnikes H. Magnetic marker monitoring: high resolution real-time tracking of oral solid dosage forms in the gastrointestinal tract. Eur J Pharm Biopharm. 2010;74(1):93–101.CrossRefGoogle Scholar
  8. 8.
    Newton JM. Gastric emptying of multi-particulate dosage forms. Int J Pharm. 2010;395(1–2):2–8.CrossRefGoogle Scholar
  9. 9.
    Fadda H, McConnell E, Short MB, Basit AW. Meal-induced acceleration of tablet transit through the human small intestine. Pharm Res. 2009;26(2):356–60.CrossRefGoogle Scholar
  10. 10.
    Coupe AJ, Davis SS, Evans DF, Wilding IR. Correlation of the gastric emptying of nondisintegrating tablets with gastrointestinal motility. Pharm Res. 1991;8(10):1281–5.CrossRefGoogle Scholar
  11. 11.
    Khosla R, Davis SS. The effect of tablet size on the gastric emptying of non-disintegrating tablets. Int J Pharm. 1990;62(2–3):R9–11.CrossRefGoogle Scholar
  12. 12.
    Khosla R, Feely LC, Davis SS. Gastrointestinal transit of non-disintegrating tablets in fed subjects. Int J Pharm. 1989;53(2):107–17.CrossRefGoogle Scholar
  13. 13.
    Katsuma M, Watanabe S, Takemura S, Sako K, Sawada T, Masuda Y, et al. Scintigraphic evaluation of a novel colon-targeted delivery system (CODES™) in healthy volunteers. J Pharm Sci. 2004;93(5):1287–99.CrossRefGoogle Scholar
  14. 14.
    Zimmermann T, Yeates RA, Laufen H, Pfaff G, Wildfeuer A. Influence of concomitant food intake on the oral absorption of two triazole antifungal agents, itraconazole and fluconazole. Eur J Clin Pharmacol. 1994;46(2):147–50.CrossRefGoogle Scholar
  15. 15.
    Davis SS, Hardy JG, Taylor MJ, Whalley DR, Wilson CG. The effect of food on the gastrointestinal transit of pellets and an osmotic device (Osmet). Int J Pharm. 1984;21:331–40.CrossRefGoogle Scholar
  16. 16.
    Rao SSC, Kuo B, McCallum RW, Chey WD, DiBaise JK, Hasler WL, et al. Investigation of colonic and whole-gut transit with wireless motility capsule and radiopaque markers in constipation. Clin Gastroenterol Hepatol. 2009;7(5):537–44.CrossRefGoogle Scholar
  17. 17.
    Sarosiek I, Selover KH, Katz LA, Semler JR, Wilding GE, Lackner JM, et al. The assessment of regional gut transit times in healthy controls and patients with gastroparesis using wireless motility technology. Aliment Pharmacol Ther. 2010;31(2):313–22.PubMedGoogle Scholar
  18. 18.
    Koziolek M, Schneider F, Grimm M, Modeβ C, Seekamp A, Roustom T, et al. Intragastric pH and pressure profiles after intake of the high-caloric, high-fat meal as used for food effect studies. J Control Release. 2015;220(Part A):71–8.CrossRefGoogle Scholar
  19. 19.
    Cassilly D, Kantor S, Knight LC, Maurer AH, Fisher RS, Semler J, et al. Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy. Neurogastroenterol Motil. 2008;20(4):311–9.CrossRefGoogle Scholar
  20. 20.
    Ewe K, Press AG, Bollen S, Schuhn I. Gastric emptying of indigestible tablets in relation to composition and time of ingestion of meals studied by metal detector. Dig Dis Sci. 1991;36(2):146–52.CrossRefGoogle Scholar
  21. 21.
    Davis SS. Formulation strategies for absorption windows. Drug Discov Today. 2005;10(4):249–57.CrossRefGoogle Scholar
  22. 22.
    Deloose E, Janssen P, Depoortere I, Tack J. The migrating motor complex: control mechanisms and its role in health and disease. Nat Rev Gastroenterol Hepatol. 2012;9(5):271–85.CrossRefGoogle Scholar
  23. 23.
    Garbacz G, Klein S, Weitschies WA. Biorelevant dissolution stress test device—background and experiences. Expert Opin Drug Deliv. 2010;7(11):1251–61.CrossRefGoogle Scholar
  24. 24.
    Schneider F, Grimm M, Koziolek M, Modeß C, Dokter A, Roustom T, et al. Resolving the physiological conditions in bioavailability and bioequivalence studies: comparison of fasted and fed state. Eur J Pharm Biopharm. 2016;108:214–9.CrossRefGoogle Scholar
  25. 25.
    Jain AK, Söderlind E, Viridén A, Schug B, Abrahamsson B, Knopke C, et al. The influence of hydroxypropyl methylcellulose (HPMC) molecular weight, concentration and effect of food on in vivo erosion behavior of HPMC matrix tablets. J Control Release. 2014;187:50–8.CrossRefGoogle Scholar
  26. 26.
    Schulze K. Imaging and modelling of digestion in the stomach and the duodenum. Neurogastroenterol Motil. 2006;18(3):172–83.CrossRefGoogle Scholar
  27. 27.
    Weitschies W, Wedemeyer RS, Kosch O, Fach K, Nagel S, Söderlind E, et al. Impact of the intragastric location of extended release tablets on food interactions. J Control Release. 2005;108(2–3):375–85.CrossRefGoogle Scholar
  28. 28.
    Weitschies W, Friedrich C, Wedemeyer RS, Schmidtmann M, Kosch O, Kinzig M, et al. Bioavailability of amoxicillin and clavulanic acid from extended release tablets depends on intragastric tablet deposition and gastric emptying. Eur J Pharm Biopharm. 2008;70(2):641–8.CrossRefGoogle Scholar
  29. 29.
    Kalantzi L, Goumas K, Kalioras V, Abrahamsson B, Dressman JB, Reppas C. Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies. Pharm Res. 2006;23(1):165–76.CrossRefGoogle Scholar
  30. 30.
    Riethorst D, Mols R, Duchateau G, Tack J, Brouwers J, Augustijns P. Characterization of human duodenal fluids in fasted and fed state conditions. J Pharm Sci. 2015:1–10.Google Scholar
  31. 31.
    FDA. Guidance for industry: food-effect bioavailability and fed bioequivalence studies. 2002.Google Scholar
  32. 32.
    Koziolek M, Grimm M, Garbacz G, Kühn JP, Weitschies W. Intragastric volume changes after intake of a high-caloric, high-fat standard breakfast in healthy human subjects investigated by MRI. Mol Pharm. 2014;11(5):1632–9.CrossRefGoogle Scholar
  33. 33.
    Diakidou A, Vertzoni M, Goumas K, Söderlind E, Abrahamsson B, Dressman J, et al. Characterization of the contents of ascending colon to which drugs are exposed after oral administration to healthy adults. Pharm Res. 2009;26(9):2141–51.CrossRefGoogle Scholar
  34. 34.
    Vertzoni M, Markopoulos C, Symillides M, Goumas C, Imanidis G, Reppas C. Luminal lipid phases after administration of a triglyceride solution of danazol in the fed state and their contribution to the flux of danazol across Caco-2 cell monolayers. Mol Pharm. 2012;9(5):1189–98.CrossRefGoogle Scholar
  35. 35.
    Litou C, Vertzoni M, Goumas C, Vasdekis V, Xu W, Kesisoglou F, et al. Characteristics of the human upper gastrointestinal contents in the fasted state under hypo- and a-chlorhydric gastric conditions under conditions of typical drug – drug interaction studies. Pharm Res. 2016;33(6):1399–412.CrossRefGoogle Scholar
  36. 36.
    Mudie DM, Amidon GL, Amidon GE. Physiological parameters for oral delivery and in vitro testing. Mol Pharm. 2010;7(5):1388–405.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Grimm M, Koziolek M, Kühn J-P, Weitschies W. Interindividual and intraindividual variability of fasted state gastric fluid volume and gastric emptying of water. Eur J Pharm Biopharm. 2018;127(February):309–17.CrossRefGoogle Scholar
  38. 38.
    Bergström CAS, Holm R, Jørgensen SA, Andersson SBE, Artursson P, Beato S, et al. Early pharmaceutical profiling to predict oral drug absorption: current status and unmet needs. Eur J Pharm Sci. 2014;57:173–99.CrossRefGoogle Scholar
  39. 39.
    Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6(3):231–48.CrossRefGoogle Scholar
  40. 40.
    Koziolek M, Carrière F, Porter CJH. Lipids in the stomach—implications for the evaluation of food effects on oral drug absorption. Pharm Res. 2018;35(3):55.CrossRefGoogle Scholar
  41. 41.
    Reppas C, Karatza E, Goumas C, Markopoulos C, Vertzoni M. Characterization of contents of distal ileum and cecum to which drugs/drug products are exposed during bioavailability/bioequivalence studies in healthy adults. Pharm Res. 2015;32(10):3338–49.CrossRefGoogle Scholar
  42. 42.
    Koziolek M, Grimm M, Becker D, Iordanov V, Zou H, Shimizu J, et al. Investigation of pH and temperature profiles in the GI tract of fasted human subjects using the Intellicap® system. J Pharm Sci. 2015;104(9):2855–63.CrossRefGoogle Scholar
  43. 43.
    Raman S, Polli JE. Prediction of positive food effect: bioavailability enhancement of BCS class II drugs. Int J Pharm. 2016;506(1–2):110–5.CrossRefGoogle Scholar
  44. 44.
    Amidon GL, Lennernäs H, Shah VP, Crison JRA. Theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12(3):413–20.CrossRefGoogle Scholar
  45. 45.
    Custodio JM, Wu C-Y, Benet LZ. Predicting drug disposition, absorption/elimination/transporter interplay and the role of food on drug absorption. Adv Drug Deliv Rev. 2008;60(6):717–33.CrossRefGoogle Scholar
  46. 46.
    Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev. 2012;64(SUPPL):163–74.CrossRefGoogle Scholar
  47. 47.
    Guiastrennec B, Söderlind E, Richardson S, Peric A, Bergstrand M. In vitro and in vivo modeling of hydroxypropyl methylcellulose (HPMC) matrix tablet erosion under fasting and postprandial status. Pharm Res. 2017;34(4):847–59.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Abrahamsson B, Albery T, Eriksson A, Gustafsson I, Sjöberg M. Food effects on tablet disintegration. Eur J Pharm Sci. 2004;22(2–3):165–72.CrossRefGoogle Scholar
  49. 49.
    Williams HD, Nott KP, Barrett DA, Ward R, Hardy IJ, Melia CD. Drug release from HPMC matrices in milk and fat-rich emulsions. J Pharm Sci. 2011;100(11):4823–35.CrossRefGoogle Scholar
  50. 50.
    Williams HD, Ward R, Hardy IJ, Melia CD. The effect of sucrose and salts in combination on the drug release behaviour of an HPMC matrix. Eur J Pharm Biopharm. 2010;76(3):433–6.CrossRefGoogle Scholar
  51. 51.
    Davis J, Burton J, Connor AL, Macrae R, Wilding IR. Scintigraphic study to investigate the effect of food on a HPMC modified release formulation of UK-294,315. J Pharm Sci. 2009;98(4):1568–76.CrossRefGoogle Scholar
  52. 52.
    Schug BS, Brendel E, Chantraine E, Wolf D, Martin W, Schall R, et al. The effect of food on the pharmacokinetics of nifedipine in two slow release formulations: pronounced lag-time after a high fat breakfast. Br J Clin Pharmacol. 2002;53(6):582–8.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Auiler JF, Liu K, Lynch JM, Gelotte CK. Effect of food on early drug exposure from extended-release stimulants: results from the Concerta®, Adderall XR™ food evaluation (CAFÉ) study. Curr Med Res Opin. 2002;18(5):311–6.CrossRefGoogle Scholar
  54. 54.
    Schug BS, Brendel E, Wonnemann M, Wolf D, Wargenau M, Dingler A, et al. Dosage form-related food interaction observed in a marketed once-daily nifedipine formulation after a high-fat American breakfast. Eur J Clin Pharmacol. 2002;58(2):119–25.CrossRefGoogle Scholar
  55. 55.
    Malaterre V, Ogorka J, Loggia N, Gurny R. Oral osmotically driven systems: 30 years of development and clinical use. Eur J Pharm Biopharm. 2009;73(3):311–23.CrossRefGoogle Scholar
  56. 56.
    O’Reilly S, Wilson CG, Hardy JG. The influence of food on the gastric emptying of multiparticulate dosage forms. Int J Pharm. 1987;34(3):213–6.CrossRefGoogle Scholar
  57. 57.
    Koziolek M, Garbacz G, Neumann M, Weitschies W. Simulating the postprandial stomach: biorelevant test methods for the estimation of intragastric drug dissolution. Mol Pharm. 2013;10(6):2211–21.CrossRefGoogle Scholar
  58. 58.
    Vardakou M, Mercuri A, Barker SA, Craig DQ, Faulks RM, Wickham MSJ. Achieving antral grinding forces in biorelevant in vitro models: comparing the USP dissolution apparatus II and the dynamic gastric model with human in vivo data. AAPS PharmSciTech. 2011;12(2):620–6.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Schneider F, Beeck R, Hoppe M, Koziolek M, Weitschies W. In vitro simulation of realistic gastric pressure profiles. Eur J Pharm Sci. 2017;107:71–7.CrossRefGoogle Scholar
  60. 60.
    Markopoulos C, Andreas CJ, Vertzoni M, Dressman JB, Reppas C. In-vitro simulation of luminal conditions for evaluation of performance of oral drug products: choosing the appropriate test media. Eur J Pharm Biopharm. 2015;93:173–82.CrossRefGoogle Scholar
  61. 61.
    Baxevanis F, Kuiper J, Fotaki N. Fed-state gastric media and drug analysis techniques: current status and points to consider. Eur J Pharm Biopharm. 2016;107:234–48.CrossRefGoogle Scholar
  62. 62.
    Berlin M, Ruff A, Kesisoglou F, Xu W, Wang MH, Dressman JB. Advances and challenges in PBPK modeling—analysis of factors contributing to the oral absorption of atazanavir, a poorly soluble weak base. Eur J Pharm Biopharm. 2015;93:267–80.CrossRefGoogle Scholar
  63. 63.
    Diakidou A, Vertzoni M, Abrahamsson B, Dressman JB, Reppas C. Simulation of gastric lipolysis and prediction of felodipine release from a matrix tablet in the fed stomach. Eur J Pharm Sci. 2009;37(2):133–40.CrossRefGoogle Scholar
  64. 64.
    Persson E, Gustafsson A-S, Carlsson A, Nilsson R, Knutson L, Forsell P, et al. The effects of food on the dissolution of poorly soluble drugs in human and in model small intestinal fluids. Pharm Res. 2005;22(12):2141–51.CrossRefGoogle Scholar
  65. 65.
    Jantratid E, Janssen N, Reppas C, Dressman JB. Dissolution media simulating conditions in the proximal human gastrointestinal tract: an update. Pharm Res. 2008;25(7):1663–76.CrossRefGoogle Scholar
  66. 66.
    Georgaka D, Butler J, Kesisoglou F, Reppas C, Vertzoni M. Evaluation of dissolution in the lower intestine and its impact on the absorption process of high dose low solubility drugs. Mol Pharm. 2017;14(12):4181–91.CrossRefGoogle Scholar
  67. 67.
    Andreas CJ, Chen YC, Markopoulos C, Reppas C, Dressman J. In vitro biorelevant models for evaluating modified release mesalamine products to forecast the effect of formulation and meal intake on drug release. Eur J Pharm Biopharm. 2015;97:39–50.CrossRefGoogle Scholar
  68. 68.
    Franek F, Holm P, Larsen F, Steffansen B. Interaction between fed gastric media (Ensure Plus®) and different hypromellose based caffeine controlled release tablets: comparison and mechanistic study of caffeine release in fed and fasted media versus water using the USP dissolution apparatus 3. Int J Pharm. 2014;461(1–2):419–26.CrossRefGoogle Scholar
  69. 69.
    Klein S. Predicting food effects on drug release from extended-release oral dosage forms containing a narrow therapeutic index drug. Dissol Technol. 2009;8:28–40.CrossRefGoogle Scholar
  70. 70.
    Fadda HM, Merchant HA, Arafat BT, Basit AW. Physiological bicarbonate buffers: stabilisation and use as dissolution media for modified release systems. Int J Pharm. 2009;382(1–2):56–60.CrossRefGoogle Scholar
  71. 71.
    Garbacz G, Kolodziej B, Koziolek M, Weitschies W, Klein S. An automated system for monitoring and regulating the pH of bicarbonate buffers. AAPS PharmSciTech. 2013;14(2):517–22.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Sheng JJ, McNamara DP, Amidon GL. Toward an in vivo dissolution methodology: a comparison of phosphate and bicarbonate buffers. Mol Pharm. 2009;6(1):29–39.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Shibata H, Yoshida H, Izutsu KI, Goda Y. Use of bicarbonate buffer systems for dissolution characterization of enteric-coated proton pump inhibitor tablets. J Pharm Pharmacol. 2016;68(4):467–74.CrossRefGoogle Scholar
  74. 74.
    Koziolek M, Görke K, Neumann M, Garbacz G, Weitschies W. Development of a bio-relevant dissolution test device simulating mechanical aspects present in the fed stomach. Eur J Pharm Sci. 2014;57:250–6.CrossRefGoogle Scholar
  75. 75.
    Chessa S, Huatan H, Levina M, Mehta RY, Ferrizzi D, Rajabi-Siahboomi AR. Application of the dynamic gastric model to evaluate the effect of food on the drug release characteristics of a hydrophilic matrix formulation. Int J Pharm. 2014;466(1–2):359–67.CrossRefGoogle Scholar
  76. 76.
    Tenjarla S, Romasanta V, Zeijdner E. Release of 5-aminosalicylate from an MMX mesalamine tablet during transit through a simulated gastrointestinal tract system. Adv Ther. 2007;24(4):826–39.CrossRefGoogle Scholar
  77. 77.
    Bellmann S, Lelieveld J, Gorissen T, Minekus M, Havenaar R. Development of an advanced in vitro model of the stomach and its evaluation versus human gastric physiology. Food Res Int. 2016:1–8.Google Scholar
  78. 78.
    Andreas CJ, Pepin X, Markopoulos C, Vertzoni M, Reppas C, Dressman JB. Mechanistic investigation of the negative food effect of modified release zolpidem. Eur J Pharm Sci. 2017;102:284–98.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Mirko Koziolek
    • 1
  • Edmund Kostewicz
    • 2
  • Maria Vertzoni
    • 3
  1. 1.Department of Biopharmaceutics and Pharmaceutical TechnologyUniversity of Greifswald, Center of Drug Absorption and TransportGreifswaldGermany
  2. 2.Institute of Pharmaceutical TechnologyGoethe UniversityFrankfurt am MainGermany
  3. 3.Department of Pharmacy, School of Health ScienceNational and Kapodistrian University of AthensAthensGreece

Personalised recommendations