Mei San
☆    

Malaysia,
2015-03-03 05:45
(3313 d 11:36 ago)

Posting: # 14533
Views: 14,990
 

 Hyoscine N-butyl­bromide 10mg Film-Coated vs Sugar Coated [Design Issues]

Hi,

Good day everyone!

May I know if anyone has any experience in conducting BE study for hyoscine IR tabs 10mg?

Is BE possible to be achieved if the reference product used in BE study is sugar-coated (Buscopan), whereas the test product is film-coated?

Appreciate feedback from all the experts!

Many thanks.

Regards,
Mei San.
Dr_Dan
★★  

Germany,
2015-03-03 11:20
(3313 d 06:01 ago)

@ Mei San
Posting: # 14535
Views: 14,284
 

 Hyoscine N-butyl­bromide 10mg Film-Coated vs Sugar Coated

Dear Mei San

❝ Is BE possible to be achieved if the reference product used in BE study is sugar-coated (Buscopan), whereas the test product is film-coated?


Yes, why not? As a quaternary ammonium compound, hyoscine butylbromide is highly polar and hence only partially absorbed following oral administration. After oral administration of single doses of hyoscine butylbromide in the range of 20 to 400 mg, mean peak plasma concentrations between 0.11 ng/mL and 2.04 ng/mL were found at approximately 2 hours. Test and reference are both IR formulations and unless they do not differ in dissolution behaviour BE should be possible. However, according to the Australian TGA ARGOM Appendix 1: Guidelines on efficacy and safety aspects of OTC applications bioequivalence data are generally not required for hyoscine butylbromide. So you may can think of a BCS class III biowaiver.

Kind regards and have a nice day
Dr_Dan
nobody
nothing

2015-03-03 17:27
(3312 d 23:54 ago)

@ Dr_Dan
Posting: # 14536
Views: 13,836
 

 Hyoscine N-butyl­bromide 10mg Flim-Coated vs Sugar Coated

...only to add that, considering data on other quaternary ammonia compounds, the extent and especially the variability of absorption might represent a substantial nightmare...

Kindest regards, nobody
Mei San
☆    

Malaysia,
2015-03-04 04:26
(3312 d 12:54 ago)

@ nobody
Posting: # 14542
Views: 13,858
 

 Hyoscine N-butylbromide 10mg Film-Coated vs Sugar Coated

❝ ...only to add that, considering data on other quaternary ammonia compounds, the extent and especially the variability of absorption might represent a substantial nightmare...


Dear nobody,

Would you mind to share more about the data on other quarternary ammonia compounds that you have encountered before or any literature sources which I can refer to?

Many thanks.
nobody
nothing

2015-03-04 09:01
(3312 d 08:20 ago)

@ Mei San
Posting: # 14544
Views: 13,774
 

 Hyoscine N-butyl­bromide 10mg Flim-Coated vs Sugar Coated

Hi Mei!

Other examples N-butyl scopolamine, trospium chloride, easy to find in Pubmed, just a very few hits ;-)

Especially for trospium there is some older data indicating nightmare, while there is a recently published BE study indicating a CVintra of only about 16%, that sounds to good to be true, I would not base my sample size estimate on that :-)

There seems to be active transport involved in the GI-absorption of these compounds...

Have fun!

Kindest regards, nobody
Mei San
☆    

Malaysia,
2015-03-04 04:32
(3312 d 12:49 ago)

(edited by Dr_Dan on 2015-03-04 08:41)
@ Dr_Dan
Posting: # 14543
Views: 13,895
 

 Hyoscine N-butyl­bromide 10mg Film-Coated vs Sugar Coated

Dear Dr Dan,

I've performed the CDP at pH 1.2,4.5, 6.8 and the F2 values calculated were 31.7, 33, 32.42 respectively. Definitely the film-coated tablet release is faster than sugar-coated tablet. Thus, still lack of confidence to proceed for the BE, taking into consideration the absorption variability and low detection amount. Is there anything I've missed out?


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! [Dr_Dan]
nobody
nothing

2015-03-04 10:20
(3312 d 07:00 ago)

@ Mei San
Posting: # 14546
Views: 13,840
 

 Hyoscine N-butylbromide 10mg Film-Coated vs Sugar Coated

Hi again!

Sugar-coating that is not removed within 10-15 min? Wow! Could you provide some details (at least mean graphs) to see what's going on there?

:-)

Kindest regards, nobody
Dr_Dan
★★  

Germany,
2015-03-04 09:56
(3312 d 07:24 ago)

@ Mei San
Posting: # 14545
Views: 13,720
 

 reformulate

Dear Mei San

During the development of a medicinal product the dissolution test is used as a tool to identify formulation factors that are influencing and may have a crucial effect on the bioavailability of the drug. You can argue that in the event that the results of comparative in vitro dissolution of the biobatches do not reflect bioequivalence as demonstrated in vivo the latter prevails. However, possible reasons for the discrepancy should be addressed and justified and honestly, I wouldn't try a study if comparative in vitro dissolution shows such demoralizing results.
As you learned so far in your case BE will be tricky and variability will be high. And then you will start with such a formulation? Forget it!

Kind regards and have a nice day
Dr_Dan
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