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elam ☆ Saudi Arabia, 2016-12-01 09:20 (3033 d 14:40 ago) Posting: # 16817 Views: 10,947 |
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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. |
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nobody nothing 2016-12-01 11:03 (3033 d 12:58 ago) @ elam Posting: # 16818 Views: 10,072 |
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...really sure about the class 1 thing? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309826/pdf/12249_2014_Article_241.pdf — Kindest regards, nobody |
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Dr_Dan ★★ Germany, 2016-12-01 14:56 (3033 d 09:05 ago) @ nobody Posting: # 16820 Views: 10,015 |
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Hi Montelukast is rapidly absorbed following oral administration. For the 10 mg film-coated tablet the mean oral bioavailability is 64%. For the 5 mg chewable tablet, the mean oral bioavailability is 73% and is decreased to 63% by a standard meal. So, no BCS class I substance (BA < 85%). But even if it would be a BCS class I substance you have the results of the BE study and you can not ignore this. — Kind regards and have a nice day Dr_Dan |
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elam ☆ Saudi Arabia, 2016-12-04 09:32 (3030 d 14:28 ago) @ nobody Posting: # 16830 Views: 9,872 |
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❝ ...really sure about the class 1 thing? ❝ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309826/pdf/12249_2014_Article_241.pdf Dear All, Thanks for your comments. Please find the USFDA reference for class I molecule. https://bpca.nichd.nih.gov/collaborativeefforts/initiatives/documents/formulations_platform_report1.pdf |
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ElMaestro ★★★ Denmark, 2016-12-01 15:50 (3033 d 08:10 ago) @ elam Posting: # 16821 Views: 10,065 |
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Hi Elam, I am hearing you ask something like "Why is a system that divides all the world's synthetic drugs into four simple categories based on permeability and solubility not a predictor of my in vivo outcome?" It is in my opinion the wrong question to ask. We haven't even understood too well why BCS sometimes is a predictor. — Pass or fail! ElMaestro |
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nobody nothing 2016-12-01 16:34 (3033 d 07:26 ago) @ ElMaestro Posting: # 16822 Views: 9,990 |
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Hmmm, not such a surprise in my opinion, if whole drug is always in solution (independent of pH) and rushes trough stomach/gut wall like a charm then no big deal in (nearly) all solid IR formulations performing identical (except for those not disintegrating in vivo). So: Class 1 is straight forward. Class III not so far from this train of though in my opinion... Edit: Please don’t shout! [Helmut] — Kindest regards, nobody |
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elam ☆ Saudi Arabia, 2016-12-04 09:59 (3030 d 14:02 ago) @ elam Posting: # 16831 Views: 9,887 |
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Hi to all, Thanks for your comments. Almost all comments are emphasizing that, Montelukast is not a BCS class I molecule. I have Understood that, we everyone have different references and dissolution study results are varying. Moreover, Please find the USFDA reference for BCS class I category. https://bpca.nichd.nih.gov/collaborativeefforts/initiatives/documents/formulations_platform_report1.pdf My earlier below mentioned questions are general. Could you please share your comments. ❝ 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? In addition, We are looking for identifying the discriminative media. Any one can advice on these? Once again thanks for your all responses. regards Elam |
Ing. Helmut Schütz