Log in
Register|
Dr_Dan ★★ Germany, 2011-04-11 12:04 (5557 d 11:16 ago) Posting: # 6884 Views: 5,181 |
|
|
Hi everybody I want to perform a BE study with orodispersible tablets. What would be the correct way to standardize the administration (with or without water and if yes how much etc.) in order to minimize variability. Your input would be very much appreciated. Kind regards Dan — Kind regards and have a nice day Dr_Dan |
|
ElMaestro ★★★ Denmark, 2011-04-11 12:24 (5557 d 10:56 ago) @ Dr_Dan Posting: # 6885 Views: 4,499 |
|
|
Dear Dr_Dan, page 22 of the holy scripture provides guidance. Apart from blahblah the most important sentence in my opinion is "Bioequivalence studies should be conducted according to the recommended use of the product." If the vols have never used such formulations before or are study-naïve they may be a bit nervous in the first period (or at least more nervous in the first than in the second). This may cause dry mouth in the first period but less so in the next etc, and can affect disperison time and thus add spurious variation. To minimise variation a bit of training therefore could be relevant. — Pass or fail! ElMaestro |
|
Dr_Dan ★★ Germany, 2011-04-11 17:32 (5557 d 05:48 ago) @ ElMaestro Posting: # 6888 Views: 4,382 |
|
|
Dear ElMaestro I have never used an orodispersible tablet myself and therefore I can not imagine what will happen. According to the guideline it is recommended wet the mouth by swallowing 20 ml of water directly before applying the ODT on the tongue. Further fluid intake is not allowed earlier than 1 hour after administration. And now my question: Should the volunteer be advised to swallow the dispersed tablet and if yes when? How can I ensure that the drug reaches the GI tract in more or less the same time in all volunteers? If the originator SmPC tells me that the ODT can also be taken as an oral suspension I think then I should prefer this kind of application, right? In this context I would like to know the amount of water you need to prepare a suspension (240 ml?). The guideline does not mention suspensions.... Kind regards Dan — Kind regards and have a nice day Dr_Dan |
|
ElMaestro ★★★ Denmark, 2011-04-11 19:10 (5557 d 04:09 ago) @ Dr_Dan Posting: # 6889 Views: 4,324 |
|
|
Dear Dr_Dan, ❝ And now my question: Should the volunteer be advised to swallow the dispersed tablet and if yes when? How can I ensure that the drug reaches the GI tract in more or less the same time in all volunteers? Very good question. Not sure I can answer without knowing the API, and not sure I can answer even if knowing the API. What did the originator do in their studies? ❝ If the originator SmPC tells me that the ODT can also be taken as an oral suspension I think then I should prefer this kind of application, right? In this context I would like to know the amount of water you need to prepare a suspension (240 ml?). The guideline does not mention suspensions.... Yes, an oral suspension would give you some advantages. This sounds to me like the API is not subject to absorption from the oral cavity but please indicate if I am mistaking this; it could make a lot of difference. I imagine the fluid restraint for one hour was made with drugs in mind that are fully or partially absorbed through the oral mucosa. From that perspective I would expect the protocol to be OK even if you allow them to swallow a glass of water after adm. But get S.A. to be safe or wait until someone with better skills comes around to answer. — Pass or fail! ElMaestro |
|
Ohlbe ★★★ France, 2011-04-12 01:01 (5556 d 22:19 ago) @ Dr_Dan Posting: # 6890 Views: 4,348 |
|
|
Dear Dan, ❝ If the originator SmPC tells me that the ODT can also be taken as an oral suspension I think then I should prefer this kind of application, right? Would be easier, but I'm not sure the BE guideline is really giving you that choice: if the reference medicinal product can be taken with or without water, bioequivalence should be demonstrated without water as this condition best resembles the intended use of the formulation. This is especially important if the substance may be dissolved and partly absorbed in the oral cavity. If bioequivalence is demonstrated when taken without water, bioequivalence when taken with water can be assumed. Regards Ohlbe — Regards Ohlbe |
Ing. Helmut Schütz