Bioequivalence and Bioavailability Forum

Phaneendra.K ☆ 2010-12-31 16:06 (5642 d 14:40 ago) Posting: # 6366 Views: 11,445	Montelukast study [Design Issues] Post reply
	Dear all, What factors are taken into account while designing a BE study of Montelukast sodium tablets. What formulation criteria, physiological factors, are taken into account Suggest me pertinent literature. Thanks and regards, Phaneendra.K — Thanks and Regards, PK

Helmut ★★★ Vienna, Austria, 2010-12-31 16:35 (5642 d 14:11 ago) @ Phaneendra.K Posting: # 6368 Views: 10,367	Montelukast study Post reply
	Dear Phani, do your homework first and search the forum for some previous posts. See also FDA’s draft guidance (2008). — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes

jagdish ☆ India, 2012-01-11 14:43 (5266 d 16:03 ago) (edited on 2012-01-12 12:14) @ Helmut Posting: # 7899 Views: 9,029	tablets Post reply
	Dear HS, can you tell me how montelukast should be administered during BE study for europen submission with water after chewing or without water after chewing

Helmut
★★★

Vienna, Austria,
2012-01-11 15:19
(5266 d 15:27 ago)

@ jagdish
Posting: # 7900
Views: 9,123

Chewable tablets (EMA)

Post reply

Dear Jagdish!

❝ Dear HS,

^^ not interested in opinions of other members?

❝ can you tell me how montelukast should be administered during BE study for european submission with water after chewing or without water after chewing

See the GL, Appendix II, Orodispersible tablets and the last paragraph:

Other oral formulations such as […] chewable tablets may be handled in a similar way as for ODTs. Bioequivalence studies should be conducted according to the recommended use of the product.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

jagdish
☆

India,
2012-01-12 12:12
(5265 d 18:34 ago)

@ Helmut
Posting: # 7912
Views: 8,973

Chewable tablets (EMA)

Post reply

Dear all,

Thank you for your reply HS,

I have gone through that guideline but it is not clear still. As per PIL, the tablet should be chewed and swallowed. But it is not clear whether it should be swallowed with water or without, as there is concern of chewed tablet particle getting stuck in teeth if swallowed without water?

Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]

Helmut
★★★

Vienna, Austria,
2012-01-13 18:26
(5264 d 12:20 ago)

@ jagdish
Posting: # 7934
Views: 9,343

Chewable tablets (EMA)

Post reply

Dear Jagdish!

❝ As per PIL, the tablet should be chewed and swallowed. But it is not clear whether it should be swallowed with water or without, […]

Do I get you right that nothing is stated in the reference’s SmPC? If yes, the first bullet point of the GL is applicable:

If the reference medicinal product can be taken with or without water, bioequivalence should be demonstrated without water as this condition best resembles the intended use of the formulation. This is especially important if the substance may be dissolved and partly absorbed in the oral cavity. If bioequivalence is demonstrated when taken without water, bioequivalence when taken with water can be assumed.

❝ as there is concern of chewed tablet particle getting stuck in teeth if swallowed without water?

Reminder: BE = similar rate and extent of absorption. If both products stick to teeth, what is the problem? If not, products might not be BE without water. Easy.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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manan ☆ Ahmedabad, 2011-01-01 07:16 (5641 d 23:30 ago) @ Phaneendra.K Posting: # 6376 Views: 10,279	Montelukast study Post reply
	Dear Phani I would like to know which type of formulation are you intersted in?? Montelukast is available as film coated and chewable tablets also. so the dosing criteria for both the formulations are going to be different. However, for any formulation, the dosing, blood sampling, plasma separation needs to be carried out under sodium vapour lamp covered with red gelatin paper.

Phaneendra.K ☆ 2011-01-02 10:32 (5640 d 20:14 ago) @ manan Posting: # 6382 Views: 10,203	Montelukast study Post reply
	Dear manan, It is Monteleukast Sodium film coated tablets. But are the criteria diffetent for different formulations. How. Also, what is the reason for the usage of monochromatic light while dosing. Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut] — Thanks and Regards, PK

Helmut
★★★

Vienna, Austria,
2011-01-02 16:13
(5640 d 14:33 ago)

@ Phaneendra.K
Posting: # 6384
Views: 10,307

FDA’s guidances, lightsensitive drugs

Post reply

Dear Phani and Manan!

❝ It is Monteleukast Sodium film coated tablets. But are the criteria diffetent for different formulations. How.

See FDA’s guidances, Section ‘Bioavailability / Bioequivalence’. There you will find a link to ‘Individual Product BE Recommendations by API’ > M > Montelukast Sodium (Granule, Tablet, Chewable Tablet). I leave it to you to check what the differences are.

❝ Also, what is the reason for the usage of monochromatic light while dosing.

Another urban myth, IMHO. I would really like to see hard data from people advocating such an error-prone procedure.
@Manan: Can you come up with a reference showing a difference, or were you just copypasting?
Concerning dosing of light sensitive drugs see this thread. A similar thread covering also bioanalytics here.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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manan
☆

Ahmedabad,
2011-01-03 06:52
(5639 d 23:54 ago)

@ Helmut
Posting: # 6386
Views: 10,323

FDA’s guidances, lightsensitive drugs

Post reply

Dear Phanni

The dosing procedure for chewable and film coated tablets is different as both fall into a different class of formulation.
As HS has said, it is always good to refer the FDA guidance on individual drugs before initiation of any study.

Dear HS
i do have a literature wherein it is mentioned that Montelukast shows instability when exposed to light leading to formation of cis-isomer as a major photoproduct and the degradation rate is least in sodium light then in UV or daylight. therefore it is better to carry out the trial in dark conditions to avoid exposure to direct light. the link which you have provided in last reply is also quiet helpful in this regard.

Helmut
★★★

Vienna, Austria,
2011-01-03 16:22
(5639 d 14:24 ago)

@ manan
Posting: # 6389
Views: 10,464

Lightsensitive drugs

Post reply

Dear Manan!

❝ i do have a literature wherein it is mentioned that Montelukast shows instability when exposed to light leading to formation of cis-isomer as a major photoproduct and the degradation rate is least in sodium light then in UV or daylight.

From the Abstract of

MM Al Omari, RM Zoubi, EI Hasan, TZ Khader and AA Badwan
Effect of light and heat on the stability of montelukast in solution and in its solid state
Journal of Pharmaceutical and Biomedical Analysis 45/3, 465-471 (2007)

Montelukast in solution showed instability when exposed to light leading to the formation of its cis-isomer as the major photoproduct. The rate of photodegradation of Montelukast in solution exposed to various light sources increases in the order of; sodium < neon < tungsten < daylight < UV (254 nm). The extent of photodegradation was influenced by solvent type, where Montelukast was found to be most stable in 70% methanol. In solid state, Montelukast showed more than 20% decrease in its potency after exposure to daylight for 1 week. Also unpacked Montelukast chewable tablets, exposed to daylight for 2 weeks, showed a decrease of about 10% with the formation of Montelukast S-oxide as a major photoproduct. On the other hand, Montelukast film-coated tablets either unpacked or in its immediate pack showed excellent stability under the same condition.

(my emphases)

❝ […] therefore it is better to carry out the trial in dark to avoid exposure to direct light.

In the light of the above: :cool:

Performing the clinical part »in dark conditions« does not make sense at all. Look at the data. Chewable tablets are expected to show a degradation of 0.03% (!!) after one hour in daylight. I don’t think it shall take that long to dispense them to the subjects.
Concerning bioanalytics – simply test it! Hint: Sometimes it’s sufficient to wrap stock solutions in aluminium foil.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

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