PMID- 21861241
OWN - NLM
STAT- MEDLINE
DCOM- 20120326
LR  - 20211020
IS  - 1530-9932 (Electronic)
IS  - 1530-9932 (Linking)
VI  - 12
IP  - 4
DP  - 2011 Dec
TI  - Quality-by-design case study: investigation of the role of poloxamer in 
      immediate-release tablets by experimental design and multivariate data analysis.
PG  - 1064-76
LID - 10.1208/s12249-011-9676-0 [doi]
AB  - 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.
FAU - Kaul, Goldi
AU  - Kaul G
AD  - Pfizer Inc., Groton, Connecticut 06340, USA. goldi.kaul@pfizer.com
FAU - Huang, Jun
AU  - Huang J
FAU - Chatlapalli, Ramarao
AU  - Chatlapalli R
FAU - Ghosh, Krishnendu
AU  - Ghosh K
FAU - Nagi, Arwinder
AU  - Nagi A
LA  - eng
PT  - Journal Article
DEP - 20110823
PL  - United States
TA  - AAPS PharmSciTech
JT  - AAPS PharmSciTech
JID - 100960111
RN  - 0 (Dosage Forms)
RN  - 0 (Pharmaceutical Preparations)
RN  - 0 (Polysorbates)
RN  - 0 (Powders)
RN  - 0 (Surface-Active Agents)
RN  - 0 (Tablets)
RN  - 059QF0KO0R (Water)
RN  - 106392-12-5 (Poloxamer)
SB  - IM
MH  - Chemistry, Pharmaceutical
MH  - Dosage Forms
MH  - Drug Compounding
MH  - Drug Stability
MH  - Kinetics
MH  - Least-Squares Analysis
MH  - *Models, Chemical
MH  - *Multivariate Analysis
MH  - Pharmaceutical Preparations/*chemistry
MH  - Poloxamer/*chemistry
MH  - Polysorbates/chemistry
MH  - Powders
MH  - Principal Component Analysis
MH  - Solubility
MH  - Surface-Active Agents/*chemistry
MH  - Tablets
MH  - Technology, Pharmaceutical/*methods
MH  - Water/chemistry
PMC - PMC3225543
EDAT- 2011/08/24 06:00
MHDA- 2012/03/27 06:00
PMCR- 2012/08/23
CRDT- 2011/08/24 06:00
PHST- 2011/02/25 00:00 [received]
PHST- 2011/08/10 00:00 [accepted]
PHST- 2011/08/24 06:00 [entrez]
PHST- 2011/08/24 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2012/08/23 00:00 [pmc-release]
AID - 9676 [pii]
AID - 10.1208/s12249-011-9676-0 [doi]
PST - ppublish
SO  - AAPS PharmSciTech. 2011 Dec;12(4):1064-76. doi: 10.1208/s12249-011-9676-0. Epub 
      2011 Aug 23.