7 replies to this topic

[suzannekurtzer]

Dissolution tests are widely used in the pharmaceutical industry to assess the influence of the formulations and manufacturing process on drug release. For example, they are used to assess the influence of aging on the formulation during stability testing. In bioequivalence studies, dissolution testing is performed to select which reference batches best match the test formulation. Finally, in some cases, these tests can be used as a surrogate for in vivo data of immediate release formulations of BCS class I and III drugs or to attain a biowaiver of strength.

The standard statistical test for comparing in vitro dissolution data with in vivo pharmacokinetic data is the F2 test. What tools are available for formulation scientists to perform F2 testing? And what regulatory guidelines must be considered when performing these tests?

Join this webinar where Prof JM Cardot will explain the following:

• When the F2 test is used to compare dissolution profiles
• The constraints of the F2 Test
• How to program this test in Phoenix
• Differences in requirements between regulatory agencies

Register now!

[LuluDurandG]

Hello,

A very good, concise and clear presentation: thanks a lot!

Just an additionnel question if possible to follow up:

Is there a minimum dissolution threshold to reach to perform a f2 (in non-sink condition)and have a meaningful result? 10%? 20%?

Thanks

[LuluDurandG]

Hello,

I saw that the webinar was recorded.

Will the recording be available from your website? I'd like to double check the data wizard functions discussed within the presentation ...

Thanks

[LuluDurandG]

If it is not too late to ask another question on F2 calculation to JM cardot:
In non-sink condition, dissolution at the same dose are recommanded in EMA guideline (eg. two tablets of 5 mg versus one tablet of 10 mg could be compared). Can dissolution at the same concentration could be used instead/accepted by EMA? (eg. one tablets of 5 mg in 500mL versus one tablet of 10 mg in 1000 mL could be compared?)

[Simon Davis]

Lucie,

   Prof Cardot has passed me the following answers;

 

q1 Is there a minimum dissolution threshold to reach to perform a f2 (in non-sink condition)and have a meaningful result? 10%? 20%?
 

To answer your question it is more by analogy to other possibilities.

For the limit of 10% we can have a justification by comparison to other dissolution requirement. Dissolution for Delayed release are 2h in acidic and then in pH 6.8. It is considered that the release is not important in acidic when it is below 10%.
So by analogy we can consider that 10% is a limit for dissolution comparison.

Reference EMA/CHMP/QWP/428693/2013
Committee for Medicinal Products for Human Use (CHMP) Guideline on quality of oral modified release products
“At least two points should be included in the specification on in vitro dissolution of a gastro-resistant product: an early time point to exclude release in the acidic medium (less than 10% dissolved after 2 hours) and one to ensure that the majority of the active substance has been released in a (near) neutral medium. It is emphasized that gastro-resistance must be demonstrated for two hours or more. With regard to acceptance criteria for continued testing, reference is made to the Ph. Eur.”

In US it is more drug related (see USP and Dissolution @ FDA).

q2 In non-sink condition, dissolution at the same dose are recommanded in EMA guideline (eg. two tablets of 5 mg versus one tablet of 10 mg could be compared). Can dissolution at the same concentration could be used instead/accepted by EMA? (eg. one tablets of 5 mg in 500mL versus one tablet of 10 mg in 1000 mL could be compared?)

No that is not possible you could compare either the same dose per vessel within your prodiuct line or test vs reference by strength.

[Simon Davis]

Just a reminder that if you go to ; https://www.certara.com/webinars/

 

you can register for his next webinar in a week's time.

 

Non-linear Time Scaling for IVIVC: Secrets from an Expert

Speaker(s): Jean-Michel Cardot

Date: March 29, 2017

Time: 11 am EST

Duration: 1 hour

 

In vitro-in vivo correlation (IVIVC) is a predictive mathematical tool that describes the relationship between an in vitro property of a drug dosage form and an in vivo pharmacokinetic response. IVIVCs generally employ linear time scaling. Yet sometimes, the IVIVC relationship is better described by a more complex function. For example, some drugs release in vivo at 2 different rates. The release rates for erodible matrices depends on the dosage form’s position in the intestine. For implants, the release rate changes as diffusion is followed by erosion.

 

If the in vitro test does not account for these possibilities, the in vitro dissolution may exhibit a different shape compared to in vivo release. In this case, a non-linear relationship must be established. Prof. JM Cardot will explain how non-parametric approaches can be used to determine time scaling.

About Our Speaker

 

Jean-Michel Cardot is a professor and head of the Department of Biopharmaceutics and Pharmaceutical Technology at the Auvergne University in France. Prior to coming to Auvergne University, he worked in the pharmaceutical industry for 15 years. Prof. Cardot earned degrees in pharmacy (PharmD), a Masters in Biopharmaceutical, Statistical sciences and Pharmacokinetics, and a doctorate in pharmaceutical sciences from Auvergne University. His research interests include biopharmaceutical development of drugs, in vitro dissolution, and in vivo bioequivalence and in vitro-in vivo correlation.

[suzannekurtzer]

Prof. Cardot gave a great webinar. If you missed it, please check out the recording.

[Simon Davis]

Webinar: How to Perform Level C IVIVC in Phoenix 13 Dec 2017

Full registration details for this complimentary webinar here; https://www.certara....vivc-in-phoenix

Speaker(s): Jean-Michel Cardot
Date: December 13, 2017
Time: 11am EDT
Duration: 1 hour

In vitro in vivo correlation (IVIVC) is built on the premise that the in vitro dissolution characteristics of a drug can serve as a surrogate for a bioequivalance study. This type of analysis is attractive to sponsors because dissolution assays are cheaper and faster to perform than clinical testing. It also provides reassurance that a positive benefit/risk balance for patients is maintained throughout the life of a drug. IVIVC encompasses levels A, B, and C.

Level C correlation relates one dissolution time point (t50%, t90%, dissolution observed at 1h, etc.) to one mean pharmacokinetic parameter such as AUC (the area under the concentration-time curve), Tmax (the time after administration of a drug when the maximum plasma concentration is reached) or Cmax (peak concentration). Only a partial relationship between absorption and dissolution is established since it does not reflect the complete shape of plasma drug concentration time curve, which is the critical factor that defines the performance of a drug product.

Due to its limitations, the usefulness of a Level C correlation is restricted in predicting in vivo drug performance. In early formulation development, Level C correlations can help select pilot formulations. Waiver of an in vivo bioequivalence study (biowaiver) is generally not possible....