A method of determining the in vivo drug release rate constant of sustained-release preparation

Assuming a one-compartment model and first-order processes for drug release, absorption, and elimination, a new equation to describe the fraction of drug to be absorbed (1-Ft) for a sustained-release product is derived. Based on this equation, when In(1-Ft) vs. time is plotted, the slopes yield the drug release rate constant (Kr), the drug absorption rate constant (Ka), and two intercepts that are a mixed function of Ka, Kr, and the fraction of sustained-release (Fs). The accuracy of this equation to generate pharmacokinetic parameters, such as Ka, Kr, Fs, and the bioavailability-volume of distribution ratio (FD/V) was tested by fitting this equation to multiple simulated plasma concentration-time data (5 sets errorless and 75 sets errant data). The absolute percentage error of Ka and FD/V estimated by this equation is much less than that of traditional polyexponential equation, whereas the absolute percentage error of Kr estimated by this equation is statistically significantly less than that of traditional polyexponential equation. Furthermore, with this equation, it is easier to estimate Fs than with traditional equation. An application of this equation in generating these parameters is illustrated for a quinidine sustained-release dosage form-quinidex.