2015-03-31 15:12
(2920 d 19:12 ago)

Posting: # 14639
Views: 5,466

 Simeticone soft gel capsule dissolution problem [Dissolution / BCS / IVIVC]

Hi all,

We are currently working on a new project in which reference product is a soft gel capsule (orally administered) and has 300 mg of simeticone (USP) and class III API in combination. Simeticone (viscous oily liquid, API grade) and class III API is mixed and filled into soft gel capsules in the reference product formulation. As generic, we are working on developing a tablet formulation. Considering information below we would like to develop a dissolution medium/method:
  • Capsule shell of reference product consists of gelatin, glycerin and colorant.
  • Simeticone is not absorbed, therefore, it has waiver for BE study.
  • Class III compound is not absorbed (or very limited); only 0.15% is absorbed and locally acts in intestins according to SPC, therefore, it has waiver for BE study.
Since we know simeticone is not dissolved, only assay of this API for this solid dosage form will take place in specification of FDF. Nevertheless, class III compound is soluble in water and though it is not absorbed and locally acts, we believe that we have to develop a dissolution method for QC purposes while submitting our dossier to MoH. We tried a dozen of dissolution medium as stated below, however, we could not succeed 100% solubility of class III API due to the fact that class III API is mixed with simeticone in the soft gel capsule and though capsule shell is dissolved simeticone (and class III API) still looks like a capsule during dissolution test.

Dissolution rate of class III API after 45 minutes, Apparatus II, (900 or 1000 ml volume):
  • 0.1 N HCl, 50 rpm: 2%
  • pH 4.5, 50 rpm: 1%
  • pH 6.8, 50 rpm: 1%
  • 0.1 N HCl (+3% SLS), 100 rpm: 10%
  • 0.1 N HCl (+3% Tween 80), 100 rpm: 7%
  • 0.1 N HCl (+20% Ethanol), 100 rpm: 3%
  • 0.1 N HCl (+5% PEG 40 Hydrogenated Castor Oil), 150 rpm: 2%
  • 0.1 N HCl (+4% cetrimide), 150 rpm: 2%
  • 0.1 N HCl (+30% tetrahydrofuran), 150 rpm: 30%
  • 0.1 N HCl (+30% tetrahydrofuran + 10% SLS), 150 rpm: 30%
As seen above, quite interesting and challenging media were studied.

Questions are:
  1. Can anyone give a clue to overcome this situation?
  2. Is it possible to give only disintegration test in specification for FDF? Can it be accepted by MoH?

Kind Regards,


2021-01-04 09:21
(815 d 00:03 ago)

@ mahonny
Posting: # 22164
Views: 848

 Simeticone soft gel capsule dissolution problem

Dear mahonny,

I read your complete post and surprise to see that you also face the same problem which we also facing in 2021.

We are also working on a similar kind of formulation where we also did the same trials as you mentioned.
Since you posted a very long time ago, so I hope you find out the solution for the SImethicone problem in Dissolution.

We are thinking to use USP Type III apparatus or looking to skip dissolution since there is very little absorption reported in the available literature.

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]
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