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Survey: calculation of the characteristics of oral diffusion-controlled release dosage forms related to the drug

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Abstract

Oral dosage forms with controlled release exhibit various advantages over their immediate release counterparts, but they must be built adequately by dispersing the drug through the well-defined polymer matrix. This study is concerned with diffusion-controlled dosage forms to resolve the problems that appear: in vitro tests generally used for determining the kinetics of drug release do not take into account the nature of the drug. On the contrary, the plasma drug profiles obtained through in vivo tests strongly depend on the nature of the drug, through their typical pharmacokinetic parameters. Moreover, the effect of the stirring rate is difficult to evaluate. Following the demand from the FDA concerned with the in vitro/in vivo correlation, a numerical model was built so as to evaluate the plasma drug profile obtained with any drug delivered from a diffusion-controlled release dosage form. The results are expressed by connecting the half-life times of the drugs obtained either with bolus injection or with the dosage forms, for various values of the parameters of interest: the diffusivity of the matrix polymer and the size of the dosage form. Thus, these diagrams make it possible to promptly determine the characteristics of the dosage forms able to give the desired plasma drug profile for any drug. Of course, for each drug being defined by its pharmacokinetic parameters, the polymer matrix should be selected as a function of its diffusivity. Finally, the evaluation of the plasma drug profile is of effective help to determine quantitatively the effect of the intervariability of the patients as well as the effect of the patient’s noncompliance.

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Abbreviations

C :

Drug concentration in the plasma

C t , C0:

Drug concentration in the plasma at time t, at time 0 (Eq. 11)

C s :

Drug concentration at the surface of the dosage form (Eq. 2)

C ext :

Drug concentration in the GI (Eq. 2)

D :

Diffusivity of the drug through the polymer dosage form cm2/s

h :

Coefficient of drug transport at the dosage form–GI liquid interface

GI:

Gastrointestinal tract

M t :

Amount of drug release by the dosage form at time t (Eqs. 3, 4)

M ∞ :

Amount of drug initially in the dosage form (Eqs. 3, 4)

M t /M∞:

Amount of drug in the plasma at time t as a fraction of the amount initially in the dosage form (Eqs. 3, 4)

n :

Number varying from 1 to ∞ (Eqs. 3, 4)

R, r:

Radius of the dosage form, radial position

t :

Time

t 0.5 :

Half-life time of the drug in the patient’s blood obtained by iv bolus injection. Pharmacokinetic parameter (Eq. 12)

T 0.5 :

Half-life of the drug in the patient’s blood with controlled release dosage form

T ′0.5 :

Half-life of the drug in the patient’s blood with immediate release dosage form

V p :

Apparent plasmatic volume (l) (Eq. 13)

Y :

Amount of drug in the GI tract at time t (Eqs. 7, 8)

Z :

Amount of drug in the plasma at time t (Eqs. 8, 9)

W :

Amount of drug eliminated at time t (Eq. 9)

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Authors and Affiliations

  1. Concordia University, Montreal, QC, Canada

    I. D. Rosca

  2. Saint-Etienne University, 42400, Saint-Etienne, France

    J. M. Vergnaud

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  1. I. D. Rosca
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  2. J. M. Vergnaud
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Correspondence to J. M. Vergnaud.

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Rosca, I.D., Vergnaud, J.M. Survey: calculation of the characteristics of oral diffusion-controlled release dosage forms related to the drug. Eur J Drug Metab Pharmacokinet 35, 29–39 (2010). https://doi.org/10.1007/s13318-010-0005-x

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  • DOI: https://doi.org/10.1007/s13318-010-0005-x

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