o ativo precisa de ar por alguma razão desconhecida à priori?

Será uma questão de pH?

Dear João and Morais, Thank you for your contributions. I may add that it seems not to be pH dependent as the same statement is included (not in the USP, but in another document) when describing the dissolution test conditions at the normally requested  physiological pH range (for dissolution profile similarity assessment). My guess is that this is not a product dependent request, but as I said it's just a guess.

BR, Luis

Hi Luis

We need to simulate the gastro-intestinal condition while performing dissolution study. As our body fluid also contains dissolved oxygen and other sort of gases. Thus there is no need to de-aerate dissolution media.

Please let me know if you find any other answer.

Wish you a nice time ahead.

Dear Prashant, I appreciate your answer those are not the reasons. The use of simulated gastric or enteric fluids as dissolution media are exceptions, not the rule. The same with deareation: the rule is to deareate the dissolution medium, so "not to deareate" is an exception. Thanks for your contribution.

Luis

Dissolved gases present in dissolution media can affect the results in a number of ways. The dissolved gas can significantly change the pH of an unbuffered solution, can interfere with the fluid-flow patterns through bubble formation, and can change the nature of the active ingre- dient and alter analytical value.

Dear Himanshu, Thank you for your contribution. However and unfortunately it does not addresses or answers my question. Kind regards

As per my perception, media which contains surfactants are not deaerated because the process results in excessive foaming, and usually the effect of dissolved air on the dissolution process is mitigated by the reduced surface tension of the medium. The dissolved gas content of deaerated media under atmospheric pressure is unstable and will tend toward saturation.

Deaeration depends also on apparatus we use...for example, dissolution tests using the flow through cell method or basket apparatus could be particularly sensitive to the deaeration of the medium. So in this case deaeration is necessary..

Sometimes it depends on formulation..for example, for disintegrating or immidiate release tablets deaeration is not required...but for nondisintegrating tablets it is required..

Dear Himanshu, The foaming could be the reason but the USP standard procedure for deaeration is "Heat the medium, while stirring gently, to about 41°, immediately filter under vacuum using a filter having a porosity of 0.45 µm or less, with vigorous stirring, and continue stirring under vacuum for about 5 min. Other validated deaeration techniques for removal of dissolved gases may be used".

I do not expect to observe foaming when filtering under vacuum. Some foam may be formed but it will disapear rapidly.

Interesting your statement regarding the disintegrating vs non-disintegrating tablets deareation requirement Could you please elaborate and/or support with some sort of reference(s). 

Thanks in advance, Luis

I do not have reference for disintegrating vs non disintegrating...this is my thinking...because we have to keep non disintegrating tablets into dissolution media for longer period of time...so if media is not deaerated then the rate may differ in this case..but for fast disintegrating tablets, the tablets remains in media for short period of time..

I may wrong in my thinking..

Dear followers of this question,

I’m updating some info I just collected, namely the matches for the expression "Do not deareate" in the USP monographs for "Oral solid" dosage forms (USP39-NF34 S1). There are “only” 5 matches (3 for montelukast and 2 for efavirenz product monographs)!!!

-----------------------------

USP Monographs: Montelukast Sodium Oral Granules

Medium: 0.5% (w/v) sodium dodecyl sulfate in water; 900 mL. Do not deaerate.

Apparatus 1: 100 mesh; 50 rpm

USP Monographs: Montelukast Sodium Tablets

Medium: 0.5% (w/v) sodium dodecyl sulfate in water; 900 mL. Do not deaerate.

Apparatus 2: 50 rpm

Time: 20 min

USP Monographs: Montelukast Sodium Chewable Tablets

Medium: 0.5% (w/v) sodium dodecyl sulfate in water; 900 mL. Do not deaerate.

Apparatus 2: 50 rpm

Time: 20 min

USP Monographs: Efavirenz Capsules

Medium: 1.0% (w/v) sodium lauryl sulfate in water; 900 mL. [Note—Do not deaerate.]

Apparatus 2: 50 rpm, with helix sinker

Time: 45 min

USP Monographs: Efavirenz Tablets

Medium: 2.0% (w/v) sodium lauryl sulfate in water; 1000 mL. Do not deaerate.

Apparatus 2: 50 rpm, with helix sinker. In addition, paddle and shaft must be composed of stainless steel and not coated with Teflon or other material. Also, all sampling devices and dissolution vessels must be washed with methanol or ethanol followed by a water wash.

Time: 30 min

---------------------------------------------

As can be seen the dissolution media SDS concentration ranges from 0.5% to 2.0% (w/v), some use the apparatus I (basket) other the App.II (paddle). Dissolution test sampling time is in the 20-45min range. I’m not able to figure out a pattern that could justify the “Do not deareate” note.

Therefore I’m still “in the dark” regarding this requirement.

Kind regards

Luis

Dear Luis,

If you see in above mentioned, the time of all the dissolution tests are 20-45 min..These all tablets and granules may be fast disintegrating or fast dissolving...I told you in previous comments that for non-disintegrating tablets the deaeration is required because without deaeration for non-disintegrating dosage form causes bubbles which may alter dissolution because we keep non-disintegrating dosage form in media until it get fully dissolved...also all of the above media contain SDS or SLS which generate bubbles or foam...

Dear Himanshu

I guess that some lost of focus has occurred in the course of the contributions from several RG members as it seems you are trying to demonstrate a link between the unusual note “Do not deaerate.” found in the USP dissolution section of the Efavirenz tablets monograph and the nature of the unit solid dosage form (disintegrating or non-disintegrating, immediate-release or slow/extended release). However, despite your belief you do not provide any facts or references to support it.

Additionally, and contrary to your statement, adding SLS (sodium lauryl sulphate) or SDS (sodium dodecyl sulphate) - they are synonymous - to the dissolution medium, reduces the formation of bubbles in the tablet surface, in the apparatus 2 paddle and shaft or in the apparatus 1, basket and shaft surfaces – and I know that from experimental observation in the lab.

Please note some additional facts from the USP39:

• Search : { USP Monographs } in 'Document Type' and { Oral Solid } in 'Dosage Form' and { Extended Release Tablets } in 'Full Text' / Found : 49 Documents
• Search : { USP Monographs } in 'Document Type' and { Oral Solid } in 'Dosage Form' and { deaerated } in 'Full Text' / Found : 69 Documents
• Search : { USP Monographs } in 'Document Type' and { Oral Solid } in 'Dosage Form' and { Dissolution 711 } in 'Monograph Section'/ Found : 779 Documents

Only 17 of the 49 Extended release tablet dissolution directions include “deaerated”, or “degassed”. The remaining 32 do not require, despite the dissolution being extended up to 24 h in some cases. Below some examples:

• Diclofenac Sodium Extended-Release Tablets (Medium:  0.05 M phosphate buffer, pH 7.5; 900 mL; Apparatus 2:  50 rpm; use wire sinkers; Times:  1, 5, 10, 16, and 24 h)
• Pentoxifylline Extended-Release Tablets (Medium: water; 900 mL or 1000 mL; Apparatus 2: 100 rpm; Times: 1, 4, 8, and 12 hours)
• Methylphenidate Hydrochloride Extended-Release Tablets (Medium:  Water; 500 mL; Apparatus 2:  50 rpm; Times:  1, 2, 3.5, 5, and 7 h)

Of 311 non extended release tablets (selected from monographs containing “deaerated”, “degassed” or “deaerate” and a dissolution specification time up to 45 minutes):

• 181 request “deaerated”, or“degassed” even with short (NMT 45 min) dissolution test times. For example: Nefazodone Hydrochloride Tablets (Medium: 0.1 N hydrochloric acid; 900 mL, deaerated.; Apparatus 2: 50 rpm.; Time: 30 minutes.)
• 5 mention the request “Do not deaerate” ---THIS IS ACTUALLY WHAT I WANT TO KNOW THE REASON WHY
• the remaining 125 do not carry any mention to medium deaeration

Additionally, you may take a look to the USP monographs on Isosorbide Mononitrate Tablets (immediate release and extended-release) and notice that the IR requires deaeration and the ER does not!

• Isosorbide Mononitrate Tablets (Medium: water; 900 mL, deaerated; Apparatus 2: 50 rpm; Time: 15 minutes)
• Isosorbide Mononitrate Extended-Release Tablets (Medium:  Water; 900 mL; Apparatus 2:  50 rpm; Tablets are placed in a metal helix prepared by winding 10 in of a 0.8-mm stainless steel wire around a 9/32-in shaft and pulling the coils to form a helix 1 in long; Times:  1, 2, 4, 8, and 12 h)

In face of the above data, retrieved from the USP, it seems that no link exists between the time length of the dissolution testing and the deaeration requirement as you stated twice already.

Therefore, despite making sense that a longer dissolution time would require the deaeration of the medium and a short would not, the fact is that it is not even the majority of the cases observed in the USP.

I welcome your comments and contribution but I also expect them to be supported by experimental data or bibliographical references.

The question still remains to be answered: Why is the Efavirenz tablet dissolution test includes a direction to "Do not deaerate" the dissolution medium? It is not dependent on the release rate, nor on the medium containing SLS, not the SLS concentration.

Kind regards

Luis

write directly to USP. for possible explaination

Dear Shiv, I already did.

Thanks and kind regards

Luis