= Sampling correction in drug release testing
<Sampling correction in drug release testing> is a material-balance adjustment for the substance removed, added or diluted when a receiver is sampled repeatedly. A measured concentration describes material still present at that moment; cumulative release also includes material withdrawn earlier. The distinction belongs to interpretation of an <in vitro drug release test>, whose transport and separation conditions are part of the measured system.<Adaptive Perfusion: A Novel In Vitro Drug Release Testing Method for Complex Drug Products by the FDA>[Technology Summary, release measurement and apparatus transport]{ref}
Let $V_n$ and $C_n$ be receiver volume and concentration just before the $n$th withdrawal. At earlier observations $j<n$, remove volume $v_j$ at concentration $C_j$ and add volume $w_j$ containing concentration $b_j$. With initial receiver amount $M_{\mathrm{init}}$, conservation gives the cumulative amount contributed by the formulation:
$$
M_{\mathrm{rel}}(t_n)=V_nC_n+\sum_{j<n}v_jC_j-\sum_{j<n}w_jb_j-M_{\mathrm{init}}.
$$
The terms account for material remaining, material already removed and material supplied from elsewhere. The equation assumes that measured species is conserved and that the receiver is well mixed; adsorption or chemical transformation requires additional terms.
For initially blank medium, blank replacement and constant volume $V$, this reduces to $VC_n+\sum_{j<n}v_jC_j$. If the aliquots are not replaced, the current volume instead satisfies $V_n=V_0-\sum_{j<n}v_j$.
Consider an illustrative receiver initially containing $100\,\mathrm{mL}$. Withdraw $10\,\mathrm{mL}$ at $C_1=0.20\,\mathrm{mg\,mL^{-1}}$ without replacement. At the next observation, $V_2=90\,\mathrm{mL}$ and $C_2=0.30\,\mathrm{mg\,mL^{-1}}$, so the cumulative amount is $27+2=29\,\mathrm{mg}$. Incorrectly retaining the initial volume in the calculation would give $32\,\mathrm{mg}$. These chosen numbers illustrate accounting, not a formulation specification.
The sampling schedule and replacement protocol must therefore accompany a release curve. A decline in concentration after dilution does not imply that previously released material returned to the carrier. Similarly, a finite-difference <drug release rate> should be calculated from corrected cumulative amounts, with uncertainty and any shared measurement errors carried through the calculation.
Back to article page
