Hi all! We have developed three prolonged formulations of our tablets with three dosage: 500, 750 and 1000 mg. And we have in vivo data of 1) IV injection (1000 mg) and 2) IR tablets (500 mg) of the same drug from our previous clinical study. I would like to predict C-t profile of our prolonge tablets using the convolution tool. We got in vitro data for these three formulations (in the same dissolution conditions). In vitro profiles of these formulations are almost the same. Our goal was to get the same behavior of three formulations with different dosage. I map a set of points of in vitro data as Input, and a set of points of in vivo data from IV and IR as UIR. After convolving I got two different predicted profiles with different Cmax and Tmax. How can I specify my dosage (500, 750 and 1000 mg) if in vitro behavior is the same for all of them? Because I need to get three predicted in vivo profiles with thee Cmax’. What kind of in vivo data (IV or IR) I have to choise? They give different sorts of profiles. I’d like to ask you to look through my sample ..maybe I did some wrong setting. Thank you, Helen [file name=Convolution_example.phxproj size=222332]/extranet/media/kunena/attachments/legacy/files/Convolution_example.phxproj[/file]Convolution_example.phxproj (217 KB)
Hi Helen, I think you should normalise the raw concs to get them the down to a single dose unit -then you have the UIR (Unit Impulse Response). Secondly I would recommend using the UIR from IV data since the IR profile maybe confounded by bioavailability, absorbtion Do you have the IVIVC tool kit as that has a wizard that helps you through some of these questions. Simon.
Hi Simon, Yes I have IVIVC tool kit. I try it. But what do you mean “you should normalise the raw concs to get them the down to a single dose unit” ? Can you explain? Thank you, Helen
In your original post you asked - "How can I specify my dosage (500, 750 and 1000 mg) if in vitro behavior is the same for all of them? Because I need to get three predicted in vivo profiles with three Cmax’. If you have normalised your UIR, by dividing the original concs by dose amount then the UIR input to the convolution will be for 1 unit.
Hi! Sorry, I do not fully understand this problem. For example: I have C-t profile of 250 mg IV injection (0, 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hr— 27.4, 17, 12.7, 7.5, 3.6, 1.5, 0.6, 0.25, 0.15, 0.13, 0.11 mg/L) (to use as UIR input) and Fdiss profile of 1000 mg CR tablets (0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16 hr — 0, 0.1, 0.18, 0.25, 0.31, 0.38, 0.43, 0.49, 0.55, 0.6, 0.66, 0.72, 0.78, 0.83, 0.89, 0.95, 0.99) (to use as input data). Please can you give me an example of the calculations of normalisation of UIR. Thank you Helen