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Mauricio Sampaio ★ Brazil, 2016-05-18 19:43 (3259 d 14:55 ago) Posting: # 16327 Views: 7,755 |
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Hello for all! I would like to confirm an information with experts in BCS.... Caffeine is a reference standard to determine the biopharmaceutical classification of other drugs according with solubility and permeability? If yes, this is a possible reason thcat support the FDA to classify caffeine as an effective substance which there are no bioequivalence problems? I really appreciate any colaboration ( with references, if is possible) , because I would like to understand why is not need to measure caffeine in bioequivalence studies. Best regards. |
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Relaxation ★ Germany, 2016-05-18 20:08 (3259 d 14:30 ago) @ Mauricio Sampaio Posting: # 16328 Views: 6,594 |
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❝ Hello for all! ❝ ❝ I would like to confirm an information with experts in BCS.... ❝ Best regards. Hello Mauricio. I am not saying that I am an expert, but I have an opinion. I am also not quite sure that I got your point, so please do not hesitate to point to my misunderstandings. I cannot check at the moment, whether caffeine is part of the list of reference standards for permeability experiments, but this could be and I think it is (highly permeable). You can find this list in the FDA-GfI "Waiver of In Vivo Bioavailability and Bioequivalence Studies...". Please note that there is a new version (including BCS-III and I am not quite sure that the title is the same (copy at home)). However, permeability is nice but not the most important issue in discussing BCS. These are actually solubility and abs. bioavailability. Just by looking at the first Google match for Caffeine solubility and bioavailability I would say, that solubility is 16 mg/mL at room temperature (increasing with temperature), that is at least 4 g are soluble in 250mL, which should be sufficient for those products I am aware of. And Blenchard et al. published 1983 that abs. BA is 108.3% in N=6. Hm, admittedly there should be better publications on this, but looks like complete absorption to me. There you go. BCS-class I. In case some other requirements are fulfilled ... no need for BE for IR products. Best regards, Steven P.S.: to avoid a misunderstanding, the solubility i refer to is in water. That would not be sufficient for a discussion of BCS, but considering the amount and that this is caffeine I would not expect to see the solubility to drop too low over the relevant pH. |
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Helmut ★★★   Vienna, Austria, 2016-05-18 20:20 (3259 d 14:19 ago) @ Relaxation Posting: # 16329 Views: 6,641 |
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Hi Steven, ❝ And Blenchard et al. published 1983 that abs. BA is 108.3% in N=6. Hm, admittedly there should be better publications on this, but looks like complete absorption to me. IMHO, F > 1 is not surprising. F > 1 is reported for theophylline, another methylxanthine (references from the 1980s somewhere in my pile; n = 12?). These are the rare examples where we have complete absorption and a first-pass metabolism in the lung. Hence, concentrations after an oral dose are higher than after IV because the pulmonary circulation is bypassed and there is no first-pass metabolism in the liver. Edit: Found them; the usual suspects…
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Mauricio Sampaio ★ Brazil, 2016-05-18 22:42 (3259 d 11:57 ago) @ Relaxation Posting: # 16330 Views: 6,734 |
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Thank you Steven and Helmult. In my opnion you are the best experts at the moment. I agree that caffeine has a behavior like BCS class 1. But, until the moment, I do not understand the reason of FDA does not request an option to waiver of in-vivo testing of this product according the Guidance for Industry: Waiver of In Vivo Bioavailability and Bioequivalence for Immediate – Release Solid Oral Dosage Forms Based on the Biopharmaceutics Classification System. Instead of this, FDA takes on that caffeine must not be measurable in bioequivalence studies as you can see in recommendations below:  Acetaminophen+ Aspirin+Caffeine Acetaminophen+Butalbital+ Caffeine Note in this guidance: Acetaminophen; Butalbital; Caffeine Capsules are a DESI1 effective drug for which there are no known or suspected bioequivalence problems, and as such is rated “AA” in the FDA/CDER’s Approved Drug Products with Therapeutic Equivalence Evaluations (“Orange Book”). Acetaminophen+Butalbital+ Caffeine+ Codeine phosphate |
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