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Modeling the pharmacokinetics of extended release pharmaceutical systems

Heat and Mass Transfer volume 45, pages 579–589 (2009)Cite this article

Abstract

The pharmacokinetic (PK) models predict the hematic concentration of drugs after the administration. In compartment modeling, the body is described by a set of interconnected “vessels” or “compartments”; the modeling consisting of transient mass balances. Usually the orally administered drugs were considered as immediately available: this cannot describe the administration of extended-release systems. In this work we added to the traditional compartment models the ability to account for a delay in administration, relating this delay to in vitro data. Firstly, the method was validated, applying the model to the dosage of nicotine by chewing-gum; the model was tuned by in vitro/in vivo data of drugs (divalproex-sodium and diltiazem) with medium-rate release kinetics, then it was applied in describing in vivo evolutions due to the assumption of fast- and slow-release systems. The model reveals itself predictive, the same of a Level A in vitro/in vivo correlation, but being physically based, it is preferable to a purely statistical method.

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Abbreviations

ADME:

Adsorption–distribution–metabolism–excretion

AUC:

Area under curve

BCS:

Biopharmaceutics classification system

ER:

Extended release

GI:

Gastro-intestinal tract

IR:

Immediate release

IVIVC:

In vitro/in vivo correlations

MEC:

Minimum effective concentration

MTL:

Minimum toxic level

PBPK:

Physiologically based pharmacokinetics

PK:

Pharmacokinetics

USP:

United States pharmacopoeia

References

  1. Fournier RL (1999) Basic transport phenomena in biomedical engineering. Taylor & Francis, Philadelphia

    Google Scholar 

  2. Saltzman M (2001) Drug delivery. Oxford University Press, Oxford

    Google Scholar 

  3. Grass GM, Sinko PJ (2002) Physiologically based pharmacokinetic simulation modelling. Adv Drug Deliv Rev 54:433–451

    Article  Google Scholar 

  4. Peppas NA, Langer R (2004) Origins and development of biomedical engineering within chemical engineering. AICHE J 50:536–546

    Article  Google Scholar 

  5. Sale M (2001) Modelling and simulation in drug development, promise and reality. Drug Discov World 2:47–50

    Google Scholar 

  6. Rooney KF, Snoeck E, Watson PH (2001) Modelling and simulation in clinical drug development. Drug Discov Today 6:802–806

    Article  Google Scholar 

  7. Holz M, Fahr A (2001) Compartment modeling. Adv Drug Deliv Rev 48:249–264

    Article  Google Scholar 

  8. Veng-Pedersen P (2001) Noncompartmentally based pharmacokinetic modeling. Adv Drug Deliv Rev 48:265–300

    Article  Google Scholar 

  9. FDA (1997) Guidance for industry. Dissolution testing of immediate release solid oral dosage forms. Center for Drug Evaluation and Research (CDER)

  10. USP 23/NF 18 (1995) The United States Pharmacopoeial Convention, Inc., Rockville, MD

  11. FDA (1997) Guidance for industry. Extended release oral dosage forms: development, evaluation, and application of in vitro/in vivo correlations. Center for Drug Evaluation and Research (CDER)

  12. McNabb ME, Ebert RV, McCusher K (1982) Plasma nicotine levels produced by chewing nicotine gum. JAMA 248:865–868

    Article  Google Scholar 

  13. Grassi M, Grassi G, Lapasin R, Colombo I (2007) Understanding drug release and absorption mechanisms. CRC Press, Boca Raton

    Google Scholar 

  14. Dutta S, Yihong Q, Samara E, Cao G, Granneman R (2005) Once-a-day extended-release dosage forms of divalproex sodium III: development and validation of a level A in vitro–in vivo correlation (IVIVC). J Pharm Sci 94(9):1949–1956

    Article  Google Scholar 

  15. FDA (2003) Guidance for industry. Bioavailability and bioequivalence studies for orally administered drug products-general considerations. Center for Drug Evaluation and Research (CDER)

  16. Korhonen O, Kanerva H, Vidgren M, Urtti A, Ketolainen J (2004) Evaluation of novel starch acetate-diltiazem controlled release tablets in healthy human volunteers. J Control Release 95:515–520

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Chemical and Food Engineering, University of Salerno, Via Ponte don Melillo, 84084, Fisciano, SA, Italy

    Michela Di Muria, Gaetano Lamberti & Giuseppe Titomanlio

Authors
  1. Michela Di Muria
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  2. Gaetano Lamberti
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  3. Giuseppe Titomanlio
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Correspondence to Gaetano Lamberti.

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Di Muria, M., Lamberti, G. & Titomanlio, G. Modeling the pharmacokinetics of extended release pharmaceutical systems. Heat Mass Transfer 45, 579–589 (2009). https://doi.org/10.1007/s00231-008-0456-7

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  • DOI: https://doi.org/10.1007/s00231-008-0456-7

Keywords

  • Diltiazem
  • Extended Release
  • Immediate Release
  • Divalproex Sodium
  • Drug Release Kinetic