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RegisterIn-vitro Dissolution: Order and questions [Regulatives / Guidelines]
Hi All,
According to 3-period bioequivalence study with Test-1, Test-2 and Reference, all products have been found as BE. But in dissolution tests in three different buffers, 60-70% of the test products and 95% of the Reference product are dissolved at first 15 min. And also ƒ2 has been found below 50.
According to the EMA guideline on the investigation of BE, 2010 CPMP/EWP/QWP/1401/98 on Appendix I:
"In case more than 85% is not dissolved at 15 minutes but within 30 minutes, at least three time points are required: the first time point before 15 minutes, the second one at 15 minutes and the third time point when the release is close to 85%."
...
"An ƒ2 value between 50 and 100 suggests that the two dissolution profiles are similar.
When the ƒ2 statistic is not suitable, then the similarity may be compared using model-dependent or model-independent methods e.g. by statistical multivariate comparison of the parameters of the Weibull function or the percentage dissolved at different time points."
Therefore, choosing 10 min as first point, 15 min as second and 25 min (close to 85% dissolved) as third point and calculating ƒ2 values at these time points at three different buffers are acceptable and adequate for authorities.
Thanks in advance.
Erkin Alkan
According to 3-period bioequivalence study with Test-1, Test-2 and Reference, all products have been found as BE. But in dissolution tests in three different buffers, 60-70% of the test products and 95% of the Reference product are dissolved at first 15 min. And also ƒ2 has been found below 50.
According to the EMA guideline on the investigation of BE, 2010 CPMP/EWP/QWP/1401/98 on Appendix I:
"In case more than 85% is not dissolved at 15 minutes but within 30 minutes, at least three time points are required: the first time point before 15 minutes, the second one at 15 minutes and the third time point when the release is close to 85%."
...
"An ƒ2 value between 50 and 100 suggests that the two dissolution profiles are similar.
When the ƒ2 statistic is not suitable, then the similarity may be compared using model-dependent or model-independent methods e.g. by statistical multivariate comparison of the parameters of the Weibull function or the percentage dissolved at different time points."
Therefore, choosing 10 min as first point, 15 min as second and 25 min (close to 85% dissolved) as third point and calculating ƒ2 values at these time points at three different buffers are acceptable and adequate for authorities.
Thanks in advance.
Erkin Alkan
Complete thread:
- In-vitro Dissolution complementary to BE sireen 2013-12-14 12:27
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- In-vitro Dissolution complementary to BE Dr_Dan 2013-12-16 12:58
- In-vitro Dissolution complementary to BE Helmut 2013-12-16 14:50
- In-vitro Dissolution: Order and questions mittyri 2014-01-22 19:39
- In-vitro Dissolution: Order and questions Dr_Dan 2014-01-23 11:50
- In-vitro Dissolution: Order and questionsErkin 2015-09-16 11:24
- In vivo ≫ in vitro Helmut 2015-09-16 15:37
- In vivo ≫ in vitro Erkin 2015-09-17 08:39
- In vivo ≫ in vitro Helmut 2015-09-17 12:41
- In vivo ≫ in vitro Shuanghe 2015-09-18 10:11
- What about BCS II, (III), IV? Helmut 2015-09-18 12:25
- In vivo ≫ in vitro Shuanghe 2015-09-18 10:11
- In vivo ≫ in vitro Helmut 2015-09-17 12:41
- In vivo ≫ in vitro Erkin 2015-09-17 08:39
- In vivo ≫ in vitro Helmut 2015-09-16 15:37
- In-vitro Dissolution: Order and questions mittyri 2014-01-22 19:39
- In-vitro Dissolution complementary to BE Helmut 2013-12-16 14:50
- In-vitro Dissolution complementary to BE Dr_Dan 2013-12-16 12:58
Ing. Helmut Schütz