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Ahmed Al Habashi
Junior

UAE,
2014-08-16 07:08

Posting: # 13394
Views: 2,595
 

 Diclofenac Potassium Powder for Oral Solution [Regulatives / Guidelines]

I would like to get your advice on the following important matter:

I have received a query from one of MOHs requesting us to justify the absence of BE study for our product “Diclofenac Potassium Powder for Oral Solution” due to presence of Mannitol (890 mg) in the formula.

They mentioned that as per the European BE guidelines, we must conduct a BE study for this product.

Hence, I request you to kindly share your experience related to this matter.

Your response will be highly appreciated.
Dr_Dan
Senior

2014-08-16 09:47

@ Ahmed Al Habashi
Posting: # 13395
Views: 2,223
 

 Diclofenac Potassium Powder for Oral Solution

Dear Ahmed Al Habashi
In general the impact of excipients on bioavailability of completely absorbable drug substances like diclofenac is considered rather unlikely but it can not be completely excluded. Therefore, even in the case of solid oral formulations with class I drugs it is advisable to use similar amounts of the same excipients in the composition of test like in the reference product. The effect of mannitol on gastro-intestinal motility is often due to concentration and a possible overlap of multiple mechanistic pathways of the excipient’s influence on drug absorption. In order to discuss the magnitude of this influence of mannitol in your formulation you could study biowaiver monographs and other scientific publications. Luckily you have two advantages: 1. your drug substance is already in solution (=no exipient's influence on solubility) and 2. diclofenac is a completely absorbable drug substances. If there is an influence (if any) this will only affect the rate but not the amount of absorption.
I hope this helps.
Kind regards
Dr_Dan

Kind regards and have a nice day
Dr_Dan
Helmut
Hero
avatar
Homepage
Vienna, Austria,
2014-08-16 13:00

@ Dr_Dan
Posting: # 13396
Views: 2,204
 

 Diclofenac Potassium Powder for Oral Solution

Dear Dan & Ahmed,

» […] The effect of mannitol on gastro-intestinal motility is often due to concentration and a possible overlap of multiple mechanistic pathways of the excipient’s influence on drug absorption. In order to discuss the magnitude of this influence of mannitol in your formulation you could study biowaiver monographs and other scientific publications.

In the biowaiver monograph we find:

“Although data in humans are lacking, data in rabbits suggest that high concentrations of os­mo­tically active excipients such as mannitol may have an impact on the tmax of acet­amino­phen.”

The monograph is from 2005; maybe newer data exist.

» 2. diclofenac is a completely absorbable drug substances. If there is an influence (if any) this will only affect the rate but not the amount of absorption.

Correct. I guess it depends on the indication. If used as an antiinflammatory I would not bother. If used as an analgetic rapid onset of effect is important, right? That’s why according to EMA’s BE-GL in vivo studies may be required even for oral solutions.

Cheers,
Helmut Schütz
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mayur661
Junior

India,
2018-11-16 09:02

@ Helmut
Posting: # 19634
Views: 397
 

 Diclofenac Potassium Powder for Oral Solution

Hello, I need your advice please for diclofenac powder for Oral Solution
should study be conducted in fasting or fed state?
thanks a lot
Ohlbe
Hero

France,
2018-11-16 10:01

@ mayur661
Posting: # 19636
Views: 393
 

 Diclofenac Potassium Powder for Oral Solution

Dear Mayur,

» please for diclofenac powder for Oral Solution should study be conducted in fasting or fed state?

In which country do you intend to submit your data ? Guidelines and requirements vary from one region to the next.

Regards
Ohlbe
mayur661
Junior

India,
2018-11-16 10:08

@ Ohlbe
Posting: # 19637
Views: 11,139
 

 Diclofenac Potassium Powder for Oral Solution

Dear Ohlbe,

» In which country do you intend to submit your data ? Guidelines and requirements vary from one region to the next.

We are intending to submit data to USA.

Dear Members,
In Package insert of diclofenac potassium for Oral solution it mentioned that
''High fat food had no significant effect on the extent of diclofenac absorption, but there was a reduction in peak plasma levels of approximately 70% after a high fat meal. Decreased Cmax may be associated to decreased effectiveness''. ''Taking CAMBIA with food may cause a reduction in effectiveness compared to taking CAMBIA on an empty stomach'' As per these statements we are going for only fasting BE study. Please provide opinion on this topic.

Thanks lot


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!
Two successive posts merged. You can edit your messages within 24 hours from posting a message [Ohlbe]
Ohlbe
Hero

France,
2018-11-16 12:09

@ mayur661
Posting: # 19639
Views: 347
 

 Fasting and fed

Dear Mayur,

» As per these statements we are going for only fasting BE study. Please provide opinion on this topic.

The draft guidances for diclofenac capsules and diclofenac potassium capsules both recommend to do fasting and fed studies. Only doing a fasting study for your powder for oral solution could be risky. I would suggest to initiate a controlled correspondence with the FDA.

Regards
Ohlbe
mayur661
Junior

India,
2018-11-16 12:27

@ Ohlbe
Posting: # 19640
Views: 333
 

 Fasting and fed

Dear Ohlbe

Thanks for your valuable suggestion
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