PMID- 18271036
OWN - NLM
STAT- MEDLINE
DCOM- 20090128
LR  - 20080903
IS  - 1520-6017 (Electronic)
IS  - 0022-3549 (Linking)
VI  - 97
IP  - 10
DP  - 2008 Oct
TI  - Quality-by-design (QbD): effects of testing parameters and formulation variables 
      on the segregation tendency of pharmaceutical powder measured by the ASTM D 
      6940-04 segregation tester.
PG  - 4485-97
LID - 10.1002/jps.21320 [doi]
AB  - The objective of this study was to examine the effects of testing parameters and 
      formulation variables on the segregation tendency of pharmaceutical powders 
      measured by the ASTM D 6940-04 segregation tester using design of experiments 
      (DOE) approaches. The test blends consisted of 4% aspirin (ASP) and 96% 
      microcrystalline cellulose (MCC) with and without magnesium stearate (MgS). The 
      segregation tendency of a blend was determined by measuring the last/first (L/F) 
      ratio, the ratio of aspirin concentrations between the first and last samples 
      discharged from the tester. A 2(2) factorial design was used to determine the 
      effects of measurement parameters [amount of material loaded (W), number of 
      segregation cycles] with number of replicates 6. ANOVA showed that W was a 
      critical parameter for segregation testing. The L/F value deviated further from 1 
      (greater segregation tendency) with increasing W. A 2(3) full factorial design 
      was used to assess the effects of formulation variables: grade of ASP (unmilled, 
      milled), grade of MCC, and amount of lubricant, MgS. MLR and ANOVA showed that 
      the grade of ASP was the main effect contributing to segregation tendency. 
      Principal Component Regression Analysis established a correlation between L/F and 
      the physical properties of the blend related to ASP and MCC, the ASP/MCC particle 
      size ratio (PSR) and powder cohesion. The physical properties of the blend 
      related to density and flow were not influenced by the grade of ASP and were not 
      related to the segregation tendency of the blend. The direct relationship between 
      L/F and PSR was determined by univariate analysis. Segregation tendency increased 
      as the ASP to MCC particle size increased. This study highlighted critical test 
      parameters for segregation testing and identified critical physical properties of 
      the blends that influence segregation tendency.
CI  - (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association
FAU - Xie, Lin
AU  - Xie L
AD  - School of Pharmacy, University of Maryland, Baltimore, Maryland, USA.
FAU - Wu, Huiquan
AU  - Wu H
FAU - Shen, Meiyu
AU  - Shen M
FAU - Augsburger, Larry L
AU  - Augsburger LL
FAU - Lyon, Robbe C
AU  - Lyon RC
FAU - Khan, Mansoor A
AU  - Khan MA
FAU - Hussain, Ajaz S
AU  - Hussain AS
FAU - Hoag, Stephen W
AU  - Hoag SW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Pharmaceutical Preparations)
RN  - 0 (Powders)
SB  - IM
MH  - Analysis of Variance
MH  - *Chemistry, Pharmaceutical
MH  - Particle Size
MH  - *Pharmaceutical Preparations
MH  - *Powders
MH  - Sensitivity and Specificity
EDAT- 2008/02/14 09:00
MHDA- 2009/01/29 09:00
CRDT- 2008/02/14 09:00
PHST- 2008/02/14 09:00 [pubmed]
PHST- 2009/01/29 09:00 [medline]
PHST- 2008/02/14 09:00 [entrez]
AID - S0022-3549(16)32757-5 [pii]
AID - 10.1002/jps.21320 [doi]
PST - ppublish
SO  - J Pharm Sci. 2008 Oct;97(10):4485-97. doi: 10.1002/jps.21320.