Bioequivalence and Bioavailability Forum

Dear Clarc

❝ In FED state:

❝ Tmax (mean) - Test: 9.8846 / Reference: 7.5385

❝ Yes it has, HPMC. The release mechanism is mostly erosion, but diffusion is implied too.

From the Tmax values in fed condition it looks like that the test formulation is having a stronger Matrix as compared to the reference.

In my experience, I have observed that higher viscosity grades of HPMC show a bit nasty behaviour in fed condition (slower release)as there will be lesser water for permatiion in formulation.

Thus most of the time we have used it in combination with lower viscosity grade HPMC or some other matix forming agents to maintain proper release.


And I agree to John on the reformulation option.

You can play with
a) different grade of HPMC (may be lower viscosity)
b) HPMC in combination with other excipients (PVP etc.)

❝ ❝ e) Was there any period effect? I know it is long shot but still it could give you some idea for AUC inf if there is a difference in Kel observed in different periods.

❝ The calculated period effect for Cmax was: 0.717 (NS)

Ok!! what about elemination pattern or Kel? Was there any differences observed in mean profile of each period.


While looking for the Indapamide MR, I came across one article which I think could be useful for you in further understanding (You must be having this one)

Galenic Development and Pharmacokinetic Profile of Indapamide Sustained Release 1.5mg; Clin Pharmacokinet 1999; 37 Suppl. 1: 13-19

Here they have played with percentages of MHPC and povidone, which permit a linear release in vitro of indapamide and later optimized the ratio of these 2 constituents to release of more than 70% of the dosage over 16 hours in a very reproducible manner.

Hope this would be of some use.

Regards