= In vitro drug release test
An <in vitro drug release test> measures the amount or rate at which a substance leaves a formulation under specified laboratory conditions. The medium, temperature, agitation or flow, separation method and sampling schedule define the experiment. A measured release curve is therefore a property of a formulation–apparatus system under those conditions, rather than a direct measurement of the concentration in a person.
A typical design places the formulation in contact with a receiving medium, separates released material from the carrier and measures concentration at several times. The primary FDA technical account describes pressure-driven separation as an alternative to passive dialysis-membrane transport for complex formulations. It emphasizes that the separation step can itself limit the observed rate.<Adaptive Perfusion: A Novel In Vitro Drug Release Testing Method for Complex Drug Products by the FDA>[Technology Summary, pressure-driven separation and limitations of conventional membrane methods]{ref}
Repeated sampling requires a material balance. Suppose a well-mixed receiver has constant volume $V$. At each observation a volume $v$ is removed and replaced with blank medium. If $C_j$ is the concentration immediately before the $j$th withdrawal, the cumulative amount transferred into the receiver by time $t_n$ is
$$
M_{\mathrm{rel}}(t_n)=VC_n+v\sum_{j=1}^{n-1}C_j.
$$
The first term is material still in the receiver; the sum is material removed at earlier observations. This <sampling correction in drug release testing> assumes matched replacement, a well-mixed receiver and no unmeasured loss or chemical transformation.
For illustrative $V=100\,\mathrm{mL}$, $v=5\,\mathrm{mL}$, $C_1=0.10\,\mathrm{mg\,mL^{-1}}$ and $C_2=0.18\,\mathrm{mg\,mL^{-1}}$, the amount at the second observation is $18+0.5=18.5\,\mathrm{mg}$, not just $18\,\mathrm{mg}$. These chosen values demonstrate accounting; they are not a formulation specification or dosing instruction.
An informative experiment also accounts for material retained in the formulation and material lost to the apparatus. Adsorption, incomplete separation or degradation can change a measured concentration without the same change in carrier release. A control without the carrier and a recovery check address different parts of this problem. Comparing the measured curve under several justified apparatus conditions helps distinguish <drug release kinetics> from transport and analytical limitations.
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