Diclofenac SR fast or fed state study design [Design Issues]

posted by balakotu – India, 2018-04-13 08:22  – Posting: # 18678
Views: 2,642

» Hello, I need your advice please for diclofenac SR 75 mg:
» should study be conducted in fasting or fed state?
» thanks a lot
» * Emea guidelines should be followed for me

Dear Norah,
"Diclofenac sodium 75 mg SR tablets" is modified release formulation.

Please be noted that, as per EMEA, we need to consider fasting, fed and multiple dose studies for Modified release (ER, SR, MR) formulations.

Please find the below statement from EMA guidelines on modified release formulations. Page number 18 & 19. {Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms (EMA/CPMP/EWP/280/96 Corr1)}

6.1.1. Studies generally required to demonstrate bioequivalence:
a single-dose fasting study comparing test and reference drug product.
a single-dose fed study using a high-fat meal comparing test and reference drug product.
a multiple-dose study comparing test and reference drug product.


We can skip the multiple dose study by showing a low extent of accumulation for the formulation. We need to show the mean AUC(0-tau) after the first dose covers more than 90% of mean AUC(0-inf) for both test and reference in fed study. (fed condition is the SmPC recommendation).
The dose is One tablet once or twice daily.
So we need to consider 12 hours as the tau (dosing interval).
If you show the mean AUC0-12 is more than 90% of the mean AUC0-inf for both test and reference in fed study, you can skip multiple dose study.

Ref: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/11/WC500177884.pdf
https://www.medicines.org.uk/emc/product/2661/smpc

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