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Use of In Vitro–In Vivo Correlation to Predict the Pharmacokinetics of Several Products Containing a BCS Class 1 Drug in Extended Release Matrices

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Abstract

Purpose

To determine if an IVIVC model can predict PK profiles of varying formulations of a BCS Class 1 drug that is a salt of a weak base.

Method

An IVIVC model (Level A) was created by correlating deconvoluted in vivo absorption data obtained from oral administration of 50 mg, 100 mg, and 200 mg fast and slow extended release formulations with in vitro percent dissolved using residual regression analysis. The model was then used to predict the in vivo profile of five test products that varied in formulation characteristics.

Results

The model passed internal validation for predicted Cmax and AUC. For external validation, in vitro data of five different test formulations was utilized. The model passed external validation for two test formulations that were different but belonging to the same release mechanism as that of the reference formulation. Three formulations failed external validation because they belonged to either a mixed or different release mechanism. The model and results were further confirmed using GatstroPlus™ simulation software.

Conclusions

These observations indicate that an IVIVC model for a BCS class I drug may be applicable to varying formulations if the principle of the drug release is similar.

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Abbreviations

AUC:

area under the curve

BCS:

biopharmaceutics classification system

Cmax :

maximum drug concentration observed in the blood plasma profile

FRA:

fraction of drug absorbed into the body

FRD:

fraction of drug dissolved during in vitro experimentation

IVIVC:

in vitro–in vivo correlation

ke :

constant of elimination

MAPE:

mean absolute percentage error

rpm:

revolutions per minute

SUPAC-MR:

scale up post approval changes modified release

Vd :

volume of distribution

%PEAUC :

percent error of AUC prediction

%PECmax :

percent error of Cmax prediction

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ACKNOWLEDGMENTS AND DISCLOSURES

The findings and conclusions in this presentation have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.

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Authors and Affiliations

  1. Food and Drug Administration Division of Product Quality Research, (CDER/OPS/OTR/DPQR), White Oak, LS Building 64 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA

    Tahseen Mirza, Srikant A. Bykadi, Christopher D. Ellison, Yongsheng Yang & Mansoor A. Khan

  2. Food and Drug Administration Division of Bioequivalence II, (CDER/OPS/OGD/DBII), 7520 Standish Place, Rockville, Maryland, 20855, USA

    Barbara M. Davit

Authors
  1. Tahseen Mirza
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  2. Srikant A. Bykadi
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  3. Christopher D. Ellison
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  4. Yongsheng Yang
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  5. Barbara M. Davit
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  6. Mansoor A. Khan
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Correspondence to Tahseen Mirza.

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Mirza, T., Bykadi, S.A., Ellison, C.D. et al. Use of In Vitro–In Vivo Correlation to Predict the Pharmacokinetics of Several Products Containing a BCS Class 1 Drug in Extended Release Matrices. Pharm Res 30, 179–190 (2013). https://doi.org/10.1007/s11095-012-0861-y

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  • DOI: https://doi.org/10.1007/s11095-012-0861-y

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