Bioequivalence and Bioavailability Forum

Hi to all,

We had conducted the Montelukast BE study (fasting) in 30 subjects (29 completed) for GCC submission. (study design: As per USFDA product specific BE guidance)

As per the study results, Cmax UL falls above the limit (128%) and point estimate is 118%.

AUC 0-t & AUC 0-inf is high but within the limits.

Results & PK analysis are clearly indicates our product is fasten in release in comparison with reference.

Here I have few questions to be clarified.

1) As per the available reference, Montelukast falls under BCS class I molecule.
In-vitro results shows that >85% release within 15 mts at release medium & pH 6.8 medium. In addition shows similarity in the 0.1 N HCl & pH 4.5 medium (No difference in release).

Here my question is what are the chances are there for failure of BCS class I molecule. Any one having experience of BCS class I molecule BE study failure?

In-vitro shows similar but in-vivo fails. We are looking for identifying the discriminative media. Any one can advice on these?

Any advice to look in to the certain parameters.

Moreover, Outlier analysis done and no outliers.

Please comment.