Bioequivalence and Bioavailability Forum

Hello John,

I am sure you are on to something; surely there might be an effect, but I have no idea if it amounts to anything tangible. I hope it will cancel out in xover trials For future purposes we will make sure to balance egg-before-juicers and juice-before-eggers in our parallel design trials.

I love this kind of speculation. There might even be a journal for it which accounts for the fact that I stopped wearing high heels.

Dear John,

Different regulatory guidelines have recommended different high-fat and high-calorie meal as a test meal for food-effect BA and fed BE studies. Which was sufficient food is given to allow potential perturbation of systemic BA of the drug from the drug product. The meal should contain approximately 30-40g of fat as this is likely to cause maximum perturbation to the release and absorption of the medicine. Similarly, protein and carbohydrate also effect the drug absorption of the drug product. Therefore it is recommended to take test medication after 30 minutes of the high-fat breakfast for uniform mixture of food particles in stomach for absorption. Different subject have different type of food intake habits. But the altimating goal was the mixture of high fat and calories of food in stomach environment which effecting the drug absorption. Similar effects was also reported in Invitro dissolution testing in different type of media e.g., 0.1N HCl (pH 2.2), pH 1.2 in SGFsp (simulated gastric fluid without pepsin), pH 6.8 in SIFsp (simulated Intestinal fluid without pancreatin, deionized water (pH approx. 5.5), fasted state simulated intestinal fluid (FaSSIF), and pH 6.5 and fed state simulated intestinal fluid (FeSSIF), pH 5.0. Hence, if subject will take food in sequential order or not, it will not effect the drug absorption in stomach as test drug will take after 30 minutes of high-fat breakfast.


Regards,
Susanta

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Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut]

Hi John,

I think this is not a silly but a technically valid question. From next time onwards consider asking the subjects to consume their meals in an uniform manner.

Regards
Srinivas

Dear John

A valid point!!

We have seen the impact on one of the BE study (BCS Class-I product)

1. In the first study all volunteers consumed their breakfast in the way they wanted (eat the egg first, then drink the juice, then eat the bread and then again drank juice): Test product values were lower by 40% and T/R was 66, 68, 68 for Cmax, AUC and AUC inf respectively)
   
2. When the same lot was used in another study where food pattern was kept like: All solid meal first→ Juice→ immediate dosing we observed T/R ratio of 96, 100 and 100 for Cmax, AUC and AUC inf respectively)

Now coming to the logic that why the second study was performed and was comfortable→ It was because the test product contained high amount of MCC and the product was not disintegrating in the churned food (USP-III) when tested in vitro with DT of about 45 minutes where as DT for reference was around 10 min. In another dissolution testing, we added some extra water above the churned food we observed the DT of ~12-15 min. But to confirm the same study was repeated and Voila

P.s: Typing from phone, sorry for spelling mistakes.