Bioequivalence and Bioavailability Forum

Dear Helmut,

Many thanks for the Excel workout and valuable info on “partial derivatives plot”.

On a second thought, can I tweak the algorithm to generate geometric progression such that the sampling is closer towards the last time point. Consider I have 18 sampling time points till 36 hours and the Cmax for my formulation is around 4 hours. I can split them in to two sets.

1. 9 sampling time points pre T_max
   
2. 9 sampling time points post T_max

I will use the existing above described algorithm for post Tmax sampling time generation [5.0, 7.0, 9.0, 12.0, 16.0, 20.0, 28.0 and 36 hrs – time points optimised for practicability].

For pre Tmax sampling time points I will use the algorithm that generates time points in a geometric progression that are closer towards the last time point [i.e. actually the Tmax].

After this exercise, if the 18 sampling time point thus generated are put together, we will have a sampling schedule which is crowded towards the T_max [ideal] and spacing out in a geometric progression on either sides.

❝ To keep it simple I would set the sampling interval to multiples of 15 minutes. We should have at least three sampling time points in the absorption phase and around C_max (FDA). So I suggest to aim for five evenly spaced samples in the interval [0, 4.75] ⇒ [0, 0.95, 1.9, 2.85, 3.8, 4.75] ⇒ mround(t,0.25) ⇒ [0, 1, 2, 2.75, 3.75, 4.75]. The remaining ten sample geometrically spaced, rounded ⇒ [6.5, 8.75, 11.75, 16, 21.5, 29, 39.25, 53.25, 72].

I totally agree with you but, just wanted to play around a bit with the algorithm. May come in handy for ER products with Tmax around 12 hours having a zero order release/absorption profile. I tried my bit with tweaking the excel algorithm but only ended up with failure .


Thanks,
IP.