Clinical assessment of the lag-time and t(max) of pellets with controlled release of glucose: in vitro/in vivo comparison using C-13-breath test
Abstract
Maintaining a stable glycaemia in diabetes mellitus type 1 requires flexible insulin administration and carbohydrate intake to affected individuals. In real life, there might be some situations limiting the insulin-sugar balance control, e.g. night sleep or prolonged sporting activities.
Glucose pellets with a pre-determined time lag between the pellet administration and glucose release were developed to mimic a snack eaten in advance'. In this article, a C-13-glucose breath test was introduced to translate laboratory dissolution testing to clinical confirmation of the glucose release pattern using 5% abundance to differentiate the appearance of in C-13 exhaled breath.
An independent two-sample t-test (p=0.20) confirmed an average clinical lag time of 300min and an in vitro time of 338min to be identical at a level of significance of =0.05. Moreover, using the same statistical method, the clinical t(max) (564min) and the in vitro t(50) (594min) were also considered identical (p=0.34).
It was concluded that dissolution testing is a relevant method to determine the time lags of dosage forms with controlled release of glucose and that the C-13-glucose breath test is a suitable clinical tool for lag time verification in clinical studies.