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Quality-by-Design Case Study: Investigation of the Role of Poloxamer in Immediate-Release Tablets by Experimental Design and Multivariate Data Analysis.

Quality-by-Design Case Study: Investigation of the Role of Poloxamer in Immediate-Release Tablets by Experimental Design and Multivariate Data Analysis.

Authors :
Kaul, Goldi
Huang, Jun
Chatlapalli, Ramarao
Ghosh, Krishnendu
Nagi, Arwinder
Source :
AAPS PharmSciTech; Dec2011, Vol. 12 Issue 4, p1064-1076, 13p
Publication Year :
2011

Abstract

The role of poloxamer 188, water and binder addition rate, on retarding dissolution in immediate-release tablets of a model drug from BCS class II was investigated by means of multivariate data analysis (MVDA) combined with design of experiments (DOE). While the DOE analysis yielded important clues into the cause-and-effect relationship between the responses and design factors, multivariate data analysis of the 40+ variables provided additional information on slowdown in tablet dissolution. A steep dependence of both tablet dissolution and disintegration on the poloxamer and less so on other design variables was observed. Poloxamer was found to increase dissolution rates in granules as expected of surfactants in general but retard dissolution in tablets. The unexpected effect of poloxamer in tablets was accompanied by an increase in tablet-disintegration-time-mediated slowdown of tablet dissolution and by a surrogate binding effect of poloxamer at higher concentrations. It was additionally realized through MVDA that poloxamer in tablets either acts as a binder by itself or promotes binder action of the binder povidone resulting in increased intragranular cohesion. Additionally, poloxamer was found to mediate tablet dissolution on stability as well. In contrast to tablet dissolution at release (time zero), poloxamer appeared to increase tablet dissolution in a concentration-dependent manner on accelerated open-dish stability. Substituting polysorbate 80 as an alternate surfactant in place of poloxamer in the formulation was found to stabilize tablet dissolution. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15309932
Volume :
12
Issue :
4
Database :
Complementary Index
Journal :
AAPS PharmSciTech
Publication Type :
Academic Journal
Accession number :
67481236
Full Text :
https://doi.org/10.1208/s12249-011-9676-0