Partial AUC & Cmax in case of multiphasic modified release drug product [Regulatives / Guidelines]

posted by maulik963 – India, 2016-05-31 10:09 (3183 d 09:22 ago) – Posting: # 16372
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Dear All,

I wish to conduct a 2-way crossover study on multiphasic modified release drug product for EMEA submission.

The drug product is a prolonged release formulation with biphasic release pattern (IR+MR). The initial maximum concentration achieves at about 1 to 2 hours (due to release of IR Part) and Peak plasma concentration achieves at about 6 to 8 hours.

As per "Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms_Jun-2015", For single dose study of multiphasic modified release drug product following parameters has to show bioequivalence.
AUC0-t, AUC0-∞, partialAUCs and Cmax in all phases.

I have kept AUC0-t, AUC0-∞, partialAUC0-2, partialAUC2-t.

Please provide your opinion on following points.

(1) Please help to understand the meaning of "Cmax in all phases".
Shall I consider it as Cmax(0-2) & Cmax(2-t)? OR shall I consider Cmax(0-t)?
Shall I report the result for Cmax(0-2) & Cmax(2-t) and prove bioequivalence only on Cmax(0-t)?

(2) As per the guideline, Cmax(x+1) and partialAUC(x+1) also need to be evaluated. In this case shall I consider it as Cmax(2+1) = Cmax0-3 & partialAUC(2+1) = partialAUC(0-3)? Please help to understand the rationale of Cmax(x+1) & partialAUC(x+1).

Thanks in advance.

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