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mahonny ☆ India, 2014-04-04 11:00 (3460 d 16:02 ago) Posting: # 12764 Views: 10,803 |
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Dear Friends, Many times i read topics in the forum and take advantage of your comments. Today i would like to ask a question for your evaluation. We are working on a fixed dose combination product. Dissolution profiles of reference and test product are given below. API1 is BCS class I drug, whereas API2 is BCS class III. Sampling points are 5-10-15-20-30-45 mins. 0.1 N HCl, 900 ml, 50 rpm, Pedal API1 R 31.9 59.1 74.7 80.4 83.7 85.2 T 25.7 52.8 76.0 88.1 92.7 93.6 API2 R 42.2 77.1 91.6 95.2 95.7 94.8 T 30.5 60.3 84.2 95.3 97.2 97.7 pH 6.8, 900 ml, 50 rpm, Pedal API1 R 21.1 48.5 72.1 83.2 88.9 92.3 T 23.0 45.2 72.1 92.3 102.8 102.4 API2 R 25.8 44.9 59.5 69.6 82.4 92.5 T 21.4 43.6 70.5 91.0 101.9 101.4 Do you think this formulation is eligible for BE study? For Class III drugs, drcampos has pointed that points earlier that 30 mins are negligible due to the fact that absorbtion is limiting step in BE study https://forum.bebac.at/mix_entry.php?id=3314 PS. API1 will be administed as one dose tablet whereas API2 will be of two doses in BE study. (Ref= A total of 3 tablets, Test= 1 tablet) Looking for your kind comments. Regards, Mahonny |
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Dr_Dan ★★ Germany, 2014-04-04 12:43 (3460 d 14:20 ago) @ mahonny Posting: # 12766 Views: 9,271 |
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Dear mahonny Keeping in mind that both drugs are good soluble the results you present look rather strange and I would not draw any conclusion from these data. I suggest to evaluate if your method is discriminatory. In case of BCS class I and III substances you would expect dissolution profiles which show a rapid onset with more than 85% dissolution after 15 min. or at least after 30 min. and about 100% at the end for each pH level. If you show this for the reference product you can evaluate if your products is suitable. I hope this helps Dr_Dan — Kind regards and have a nice day Dr_Dan |
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mahonny ☆ India, 2014-04-04 13:12 (3460 d 13:51 ago) @ Dr_Dan Posting: # 12767 Views: 9,298 |
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Dear Dr_Dan, API3 is class III according to literature, however, API1 which is dexketoprofen trometamol, is expected to be class I (or class III). We could not find any knowledge in the literature survey. Below is given 75 rpm dissolution data of reference product of API1. If we study at 75 rpm, %85 dissolution in 15 minutes is achived, however, i do think that 75 rpm dissolution might not reflect biorelevant conditions. What do you think? To consider 75 rpm data or 50 rpm? In the case of considering 75 rpm data, any formulation possessing >%85 dissolution in 15 minutes will be suitable but i am very suspicious that it is biorelevant. Besides, i believe that main reason for relatively low solubility at 50 rpm is the particle size of the API1 in reference product. 0.1 N HCl, 900 ml, 75 rpm, Pedal API1 R 43.0 79.9 90.7 93.3 94.7 95.2 95.0 API2 R 54.3 92.3 95.0 94.2 93.4 92.2 pH 6.8, 900 ml, 75 rpm, Pedal API1 R 43.6 77.1 99.6 99.5 98.5 97.4 96.4 API2 R 32.1 57.7 74.0 83.9 91.4 93.5 Regards, Mahonny 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] — Mahonny |
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Dr_Dan ★★ Germany, 2014-04-04 14:43 (3460 d 12:19 ago) @ mahonny Posting: # 12768 Views: 9,323 |
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Dear mahonny, I do not believe that main reason for relatively low solubility at 50 rpm is the particle size of the API1 in reference product since large particles dissolve more slowly indeed but at the end completely so that you will get 100% dissolution even if the profile is different. But you show differences in the proportion of dissolved API between your test and the reference formulation. I suggest to perform some more solubility and dissolution tests. On basis of the presented data I would not dare to give advice. Kind regards Dr_Dan — Kind regards and have a nice day Dr_Dan |
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mahonny ☆ India, 2014-04-04 15:29 (3460 d 11:33 ago) @ mahonny Posting: # 12769 Views: 9,279 |
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Any more comments from different point of views are highly appreciated... — Mahonny |
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luvblooms ★★ India, 2014-04-07 10:28 (3457 d 16:34 ago) @ mahonny Posting: # 12778 Views: 9,299 |
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Dear Mahonny ❝ Any more comments from different point of views are highly appreciated...
As said, you should look for some more solubility and dissolution tests. With the current data I would be worried for my BE out come. Regards — ~A happy Soul~ |
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mahonny ☆ India, 2014-04-14 17:22 (3450 d 09:41 ago) @ luvblooms Posting: # 12836 Views: 9,113 |
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@luvblooms Thanks for your comments. ❝ a. Was there any heap formation at 50 rpm? The difference between 50 and 75 rpm points towards. Heap is formed, that is right. But currently we have only reference tablets for BE study, therefore, we dont want to change the DT method :s ❝ b. Why not trying basket apparatus and check? Basket method was tried as well, however heap still remains Edit: Standard quotes restored. [Helmut] — Mahonny |
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susan dong ☆ China, 2018-11-26 09:35 (1763 d 16:27 ago) @ mahonny Posting: # 19650 Views: 4,397 |
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I want to know when to use the dissolution sinker. I see from this website (https://www.zhehanfilter.com/dissolution-accessories/dissolution-sinker.html) that the use of dissolution sinker may affect the test results, is that so? 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! [Ohlbe] |
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snow2020 ☆ India, 2018-12-05 07:27 (1754 d 18:36 ago) @ susan dong Posting: # 19667 Views: 4,244 |
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Thank you for your suggestion. I checked the website you gave. would like to ask, does this dissolution sinker have an impact on the test results? |
Ing. Helmut Schütz