Dissolution Assay Development for in Vitro-in Vivo Correlations

Theory and Case Studies
  • Brian R. Rohrs
  • John W. Skoug
  • Gordon W. Halstead
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 423)


To obtain an in vitro-in vivo relationship (IVIVR), two sets of data are needed. The first set is the in vivo data, usually a pharmacokinetic metric derived from a plasma concentration profile (e.g., AUC, Cmax, % Absorbed, etc.). The second data set is the in vitro data. This is usually drug release data from a dissolution test and most often takes the form of percent dissolved as a function of time. A mathematical model describing the relationship between these data sets is then developed. While fairly obvious, it should be pointed out that when trying to develop an IVIVR, the in vivo data is fixed. Once this data is generated, it establishes the relevant performance of a particular dosage form or series of formulations. The in vitro drug release profile, on the other hand, may be modified through changes in the dissolution test conditions. It is the goal of the pharmaceutical scientist to vary in vitro conditions such that a dosage form or formulation series behaves in a manner similar to that found in vivo.


Response Surface Drug Release Dissolution Medium Dissolution Profile Dissolution Test 


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  1. 1.
    Pharmacopeial Forum, July–Aug 1981, p 1226.Google Scholar
  2. 2.
    Abdou HM. Dissolution, bioavailability and bioequivalence. Easton, PA: Mack Publishing Company, 1989, p l65.Google Scholar
  3. 3.
    Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995;12: 413–20.PubMedCrossRefGoogle Scholar
  4. 4.
    Skoug JW, Halstead GW, Theis DL, Freeman JE, Fagan DT, Rohrs BR. Strategy for the development and validation of dissolution tests for solid oral dosage forms. Pharm Tech 1996; 20:5: 58–72.Google Scholar
  5. 5.
    Civiale C, Ritschel WA, Shiu GK, Aiache JM, Beyssac E. In vivo-in vitro correlation of salbutamol release from a controlled release osmotic pump delivery system. Meth Find Exp Clin Pharmacol 1999; 13(7): 491–498.Google Scholar
  6. 6.
    U.S. Pharmacopeia 1995 Chapter 711, Dissolution.Google Scholar
  7. 7.
    Box GEP, Hunter WG, Hunter JS. Statistics for experimenters, an introduction to design, data analysis, and model building. New York: John Wiley & Sons, 1978.Google Scholar
  8. 8.
    Skoug JW, Borin MT, Fleishaker JC, Cooper AM. In vitro and in vivo evaluation of whole and half tablets of sustained-release adinazolam mesylate. Pharm Res 1991; 8(12): 1482–87.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1997

Authors and Affiliations

  • Brian R. Rohrs
    • 1
  • John W. Skoug
    • 1
  • Gordon W. Halstead
    • 1
  1. 1.Pharmaceutical DevelopmentPharmacia and UpjohnKalamazooUSA

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