Vishal S
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India,
2021-05-24 11:21
(1153 d 03:08 ago)

Posting: # 22363
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 bioequivalence if test and reference formulation having different strengths [Design Issues]

How to prove the bioequivalence if test formulation having strength 325 mg and reference formulation having strength 500 mg


Edit: Category changed; see also this post #1. Please follow the Forum’s Policy[Helmut]
Helmut
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Vienna, Austria,
2021-05-24 14:32
(1152 d 23:58 ago)

@ Vishal S
Posting: # 22364
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 least common multiple of T and R

Hi Vishal,

❝ How to prove the bioequivalence if test formulation having strength 325 mg and reference formulation having strength 500 mg


When administering single doses, such a large dose-correction will not be acceptable (see there). I did it once 20 years ago when strict dose-proportionality was known for R and proven for T in another study. It was accepted by the German BfArM but we were told at the same time “Please do that never again.”

You would need to administer the least common multiple of the strengths (6,500 mg), i.e., 20 units of T and 13 units of R. This will be difficult even if this single dose is within the approved range.

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Vishal S
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India,
2021-05-25 15:26
(1151 d 23:03 ago)

@ Helmut
Posting: # 22365
Views: 2,123
 

 least common multiple of T and R

Hii Helmut

Thank you for replay
we are designing the fixed dose combination Immediate release test formulation(A+B) having strength 100 mg (A) and 325 mg (B), RLD for FDC formulation not approved in EU market & not available so we are using two different RLDs ie RLD (A) of 100 mg strength and RLD (B) having 500 mg strength. Note than RLD (B) available in EU market in 500 mg strength, 325 mg strength not available as RLD.
please guide me for BE study for same

Thanks and Regards
Vishal S


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 #5! [Ohlbe]
drgunasakaran1
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2021-05-25 16:22
(1151 d 22:08 ago)

@ Vishal S
Posting: # 22366
Views: 2,094
 

 least common multiple of T and R

Dear Mr Vishal,

❝ we are designing the fixed dose combination Immediate release test formulation(A+B) having strength 100 mg (A) and 325 mg(B), RLD for FDC formulation not approved in EU market & not available so we are using two different RLDs ie RLD (A) of 100 mg strength and RLD (B) having 500 mg strength. Note than RLD (B) available in EU market in 500 mg strength, 325 mg strength not available as RLD.


If possible, can we know the name of molecules to understand the rationale of individual strengths in the proposed FDC and to assess the clinical advantages of proposed FDC against the use on monotherpies.
Is it Aceclofenac/Paracetamol 100/325 mg FDC formulation??

Dr S Gunasakaran MBBS MD
Disclaimer: The replies/posts are my personal opinions and it does not represent my company views on the same.
Helmut
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Vienna, Austria,
2021-05-26 02:23
(1151 d 12:06 ago)

@ Vishal S
Posting: # 22367
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 least common multiple of T and R

Hi Vishal,

❝ we are designing the fixed dose combination Immediate release test formulation(A+B) […] 325 mg(B) […] Note than RLD (B) available in EU market in 500 mg strength, 325 mg strength not available as RLD.

  1. There are no reference-listed drugs in Europe.
  2. Did you bother reading the section I linked in my previous post? BE means always comparing BA of the same doses. An adjustment$$\small{\frac{f_\textrm{T}}{f_\textrm{R}}=\frac{AUC_\textrm{T}\,\cdot D_\textrm{R}}{AUC_\textrm{R}\,\cdot D_\textrm{T}}}$$would not be acceptable.

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