Bioequivalence and Bioavailability Forum

Dear All,
we had worked on angiotensin receptor antagonist. The molecule has inherent variability.
It has bioavailability of 13 % and also has a regiospecific absorption (from duodenum to jejunum). We carried study where we compared two test formulations with the innovator. The study was completed in three period. The study was marginally failed. when the data was analysed, it was observed that the varibaility in period three was on higher side as compared to period 1 and 2. The higher variability in period three is irrespective of the formulations dosed to the healthy volunteers. The variability in Cmax is given below.

Formulations % CV values
           TestProduct1   TestProduct2     Reference        
Period 1       34.94          35.61          65.89
Period 2       34.81          34.59          42.48
Period 3       26.61          28.22          50.57

The 90 % CI values are given below
                 Cmax          AUC 0-t       AUC 0-inf
(T2 Vs R)    72.05-101.45    69.63-98.88    70.31-97.80
(T1 Vs R)    66.36- 93.43    67.83-96.33    68.95-95.90

The dissolution profiles of the molecule are carried out in multi pH media (0.1 N HCl, pH 4.5, pH 6.8 and pH7.4)

The molecule is insoluble at pH 4.5 (2-3 % dissolution) while it is sparingly soluble in acid and has good solubility above pH 6.0. The dissolution profile of the in house test product is matching in all media with that of innovator.

Considering the above results, we are unable to understand the causes of failure in BE study.
Kindly suggest
Regards
Rahul

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