Permutation Test (PT) and Tolerated Difference Test (TDT): two new, robust and powerful nonparametric tests for statistical comparison of dissolution profiles.

2.50
Hdl Handle:
http://hdl.handle.net/10033/293160
Title:
Permutation Test (PT) and Tolerated Difference Test (TDT): two new, robust and powerful nonparametric tests for statistical comparison of dissolution profiles.
Authors:
Gómez-Mantilla, José-David; Casabó, Vicente Germán; Schaefer, Ulrich F; Lehr, Claus-Michael
Abstract:
The most popular way of comparing oral solid forms of drug formulations from different batches or manufacturers is through dissolution profile comparison. Usually, a similarity factor known as (f2) is employed; However, the level of confidence associated with this method is uncertain and its statistical power is low. In addition, f2 lacks the flexibility needed to perform in special scenarios. In this study two new statistical tests based on nonparametrical Permutation Test theory are described, the Permutation Test (PT), which is very restrictive to confer similarity, and the Tolerated Difference Test (TDT), which has flexible restrictedness to confer similarity, are described and compared to f2. The statistical power and robustness of the tests were analyzed by simulation using the Higuchi, Korsmayer, Peppas and Weibull dissolution models. Several batches of oral solid forms were simulated while varying the velocity of dissolution (from 30 min to 300 min to dissolve 85% of the total content) and the variability within each batch (CV 2-30%). For levels of variability below 10% the new tests exhibited better statistical power than f2 and equal or better robustness than f2. TDT can also be modified to distinguish different levels of similarity and can be employed to obtain customized comparisons for specific drugs. In conclusion, two new methods, more versatile and with a stronger statistical basis than f2, are described and proposed as viable alternatives to that method. Additionally, an optimized time sampling strategy and an experimental design-driven strategy for performing dissolution profile comparisons are described.
Affiliation:
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus A4.1, D-66123 Saarbruecken, Germany.
Citation:
Permutation Test (PT) and Tolerated Difference Test (TDT): two new, robust and powerful nonparametric tests for statistical comparison of dissolution profiles. 2013, 441 (1-2):458-67 Int J Pharm
Journal:
International journal of pharmaceutics
Issue Date:
30-Jan-2013
URI:
http://hdl.handle.net/10033/293160
DOI:
10.1016/j.ijpharm.2012.11.008
PubMed ID:
23194886
Type:
Article
Language:
en
ISSN:
1873-3476
Appears in Collections:
publications of the department drug delivery ([TC] DDEL)

Full metadata record

DC FieldValue Language
dc.contributor.authorGómez-Mantilla, José-Daviden_GB
dc.contributor.authorCasabó, Vicente Germánen_GB
dc.contributor.authorSchaefer, Ulrich Fen_GB
dc.contributor.authorLehr, Claus-Michaelen_GB
dc.date.accessioned2013-05-31T14:18:18Zen
dc.date.available2013-05-31T14:18:18Zen
dc.date.issued2013-01-30en
dc.identifier.citationPermutation Test (PT) and Tolerated Difference Test (TDT): two new, robust and powerful nonparametric tests for statistical comparison of dissolution profiles. 2013, 441 (1-2):458-67 Int J Pharmen_GB
dc.identifier.issn1873-3476en
dc.identifier.pmid23194886en
dc.identifier.doi10.1016/j.ijpharm.2012.11.008en
dc.identifier.urihttp://hdl.handle.net/10033/293160en
dc.description.abstractThe most popular way of comparing oral solid forms of drug formulations from different batches or manufacturers is through dissolution profile comparison. Usually, a similarity factor known as (f2) is employed; However, the level of confidence associated with this method is uncertain and its statistical power is low. In addition, f2 lacks the flexibility needed to perform in special scenarios. In this study two new statistical tests based on nonparametrical Permutation Test theory are described, the Permutation Test (PT), which is very restrictive to confer similarity, and the Tolerated Difference Test (TDT), which has flexible restrictedness to confer similarity, are described and compared to f2. The statistical power and robustness of the tests were analyzed by simulation using the Higuchi, Korsmayer, Peppas and Weibull dissolution models. Several batches of oral solid forms were simulated while varying the velocity of dissolution (from 30 min to 300 min to dissolve 85% of the total content) and the variability within each batch (CV 2-30%). For levels of variability below 10% the new tests exhibited better statistical power than f2 and equal or better robustness than f2. TDT can also be modified to distinguish different levels of similarity and can be employed to obtain customized comparisons for specific drugs. In conclusion, two new methods, more versatile and with a stronger statistical basis than f2, are described and proposed as viable alternatives to that method. Additionally, an optimized time sampling strategy and an experimental design-driven strategy for performing dissolution profile comparisons are described.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to International journal of pharmaceuticsen_GB
dc.titlePermutation Test (PT) and Tolerated Difference Test (TDT): two new, robust and powerful nonparametric tests for statistical comparison of dissolution profiles.en
dc.typeArticleen
dc.contributor.departmentBiopharmaceutics and Pharmaceutical Technology, Saarland University, Campus A4.1, D-66123 Saarbruecken, Germany.en_GB
dc.identifier.journalInternational journal of pharmaceuticsen_GB

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.