P. Veng-pedersen et al., Carbamazepine level-A in vivo-in vitro correlation (IVIVC): A scaled convolution based predictive approach, BIOPHARM DR, 21(1), 2000, pp. 1-6
A method is presented for prediction of the systemic drug concentration pro
file from in vitro release/dissolution data for a drug formulation. The met
hod is demonstrated using four different tablet formulations containing 200
mg carbamazepine (CZM), each administered in a four way crossover manner t
o 20 human subjects, with 15 blood samples. drawn to determine the resultin
g concentration profile. Amount versus time dissolution data were obtained
by a 75 rpm paddle method for each formulation. Differentiation, with respe
ct to time, of a monotonic quadratic spline fitted to the dissolution data
provided the dissolution rate curve. The dissolution curve was through time
and magnitude scaling mapped into a drug concentration curve via a convolu
tion by a single exponential, and the estimated unit impulse response funct
ion. The method was tested by cross-validation, where the in vivo concentra
tion profiles for each formulation were predicted based on correlation para
meters determined from in vivo-in vitro data from the remaining three formu
lations. The mean prediction error (MPE), defined as the mean value of 100%
x(observed -predicted)/observed was calculated for all 240 cross-validatio
n predictions. The mean values of MPE were in the range of 10-36% (average
220%) with standard deviations (S.D.s) in the range of 9-33% (average 13%),
indicating a good prediction performance of the proposed in vivo-in vitro
correlation (IVIVC) method. Copyright (C) 2000 John Wiley & Sons, Ltd.