Bioequivalence and Bioavailability Forum

Dear Samaya

❝ What kind of conclusion can be drawn from dissolution / disintegration behaviour of formulation in fed viscous media when there isn't a significant difference between Tmax of T and R? (No lagtime and both T and R have 7.6 - 8 hr Tmax)... Out of curiosity!!

No T lag, means absorption starts from upper part of GIT or there might be a chance of Cmax build-up through hepatic recirculation (Typical example Raloxifene)
You can get few ideas as

1. Difference in disintegration pattern between test and reference product (for example: if disintegration of test is faster and there is saturation metabolism, absorption rate and exposure would be higher or if release from test formulation is slow as compared to reference, it would behave like an SR product leading to lower Cmax and/or AUC values): I would rather first try to find out the reason behind the difference and minimize it.
   
   
2. The differences in release mechanism in fed condition: Normally food forms a layer around the formulation and modifies the release mechanism. And it was observed that if you change some common excipients (MCC in place of Lactose), the release rate and disintegration pattern change drastically and show impact on BE studies as well.
   
   
3. And things get further interesting where Intestinal Glucuronidation is involed or where there is interplay of PgP and CYP 3A4.

Try this paper
Jelena Parojčić, Dragana Vasiljević, Svetlana Ibrić, Zorica Djurić; Tablet disintegration and drug dissolution in viscous media: Paracetamol IR tablets; International Journal of Pharmaceutics 355 (2008) 93–99
And also check some back refrences.


Hope this will give you some food for thought