Central Composite Experimental Designs

Applied to Chemical Systems

John A. Palasota and Stanley N. Deming1
University of Houston, 4800 Calhoun Road, Houston, TX 77204-5641

Multifactor Systems in Chemistry

In science there has always been a strong belief that “if
you want to find out how one factor influences a response,
you must hold all other factors constant and vary only that
one factor.” As a result, much research is still carried out
using the single-factor-at-a-time method (I).
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For chemical systems that have more than one indepen-

dent variable or factor (multifactor systems), the single-
factor-at-a-time method often leads to an incomplete un-
derstanding of the behavior of the system, resulting in
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confusion and a lack of predictive ability. Some of this con-

fusion may be avoided with the application of properly de-
signed experiments and adequate multifactor models.

Response Surfaces
Figures 1-3 show typical response surfaces that are fre-
quently encountered in chemistry. A response surface is a
plot of the system response (e.g., percent yield of a reac-
tion) versus each of the factors or variables that have an
influence on the response (e.g., temperature and pressure)
(2, 3).

A Maximum
For Figure 1, suppose that the following factors are rep-
resented by the following variables. Figure 2. Response surface for the full two-factor second-order poly-
nomial model.
The response y\ is the percent yield.
y2 = 96.65 1.683X, 2.183x2 + 0.01250(^)2
- -

The factor x1 is the reaction temperature.

The factor x2 is the reaction pressure. + 0.01750(x2)2 + 0.008660^2

Then at a reaction temperature of 50 °C and a reaction

pressure of 50 atmospheres, the percent yield is 100%. At
any other temperature and pressure, the percent yield is
less than 100%.

A Minimum

Chemical systems often have multiple responses. For ex-

ample, in the reaction described above, both high percent
yield and low percent impurity might be desirable. Figure
2 might show a response surface of percent impurity (re-
sponse y2) versus reaction temperature (factor xi) and re-
action pressure (factor x2).
At a reaction temperature of 50 °C and a reaction pres-
sure of 50 atmospheres in Figure 2, the percent impurity is
a minimum. At any other temperature and pressure, the
percent impurity is greater than the minimum. Thus, if
the reaction is run at 50 °C and 50 atmospheres, the per-
cent yield (Fig. 1) will be a maximum, while the percent
impurity (Fig. 2) will be a minimum.
A Saddle Surface

Figure 3 illustrates a third response surface often en-

Figure 1. Response surface for the full two-factor second-order poly- countered in chemistry: a saddle surface (4). Let the re-
nomial model.
y, = 3.349 + 1.683*, + 2.183x2 0.01250^)2
-

1
Author to whom correspondence should be addressed. (713) 743-
-

0.01 750(x2)2 -

0.008660x1x2 2809.

560 Journal of Chemical Education

 30

25
(0, +1.41)
319

,00 20 -

6 0

*0
5 -

!°
0 -'-:-1-1-1-
0 5 10 15 20 25 30

Drops H202

Figure 4. A two-factor central composite design.

A significant interaction between factor x, and factor x2

Figure 3. Response surface for the full two-factor second-order poly-
nomial model.
y, 93.30 0.3660*, 1,366*2 0.005000(x,)2
= - - -
+ 0.005000<*2)2
sponse y, be the percent yield for a different reaction as a
function of temperature (factor X|) and pressure (factor x2)-
As the experimental conditions change from a tempera-
ture of 50 °C and a pressure of 50 atmospheres, the percent
yield either increases or decreases depending on the direc-
tion. Increasing or decreasing both temperature and pres-
sure causes the percent yield to increase. Increasing one
factor while decreasing the other factor causes the percent
yield to decrease.
The Polynomial Model
A full second-order polynomial empirical model is often
adequate for describing a wide variety of multifactor chem-
ical systems such as those shown in Figures 1—3. For a two-
factor system the model is
yii -
can be seen in Figure 3. When xi = 0, as x2 increases, the
response decreases. However, when Xi = 100, as x2 in-
creases, the response increases. Thus, the response surface
has the appearance of a twisted plane.
The Central Composite Design
+ 0.01732*,*2 Assuming that the model of eq 1 will adequately describe
the behavior of a two-factor system, it is necessary to
choose an experimental design that will provide sufficient
data to estimate the p’s. Box and Wilson (8) introduced the
central composite design in 1951. A central composite de-
sign (Fig. 4) consists of a two-level full factorial design (tri-
angles) superimposed on a star design (dots). The centers
of the two designs coincide (9, 10).
This design allows the estimation of the intercept, slope,
curvature, and interaction terms in the model of eq 1. In a
coded factor space, in which the factorial points are ±1
from the center, the star points are usually located a dis-
tance
a = 2*/4
from the center, where k is the number of factors (2).
A coded central composite design (11) for a system with
two factors (k = 2) is listed in the table. The two factors (xi
and x2) might be pH and viscosity, temperature and pres-

Pa + Pl*li + Pa*2i + Pll(xli)2 + P22(x2;)2 + 012*1[*2: + rli (1)

sure, or volume of reactant A and volume of reactant B.
The coded values in the design matrix represent the fol-
whereyii is the single response in the ith experiment (e.g.,
absorbance); xi and x2 are the factors or experimental vari- lowing values that the two factors take for this particular
ables (e.g., concentration of reactant A and concentration design in a specified region of factor space.
of reactant B); p0 is the intercept term; pi and p2 are slopes • the lowest value: -a
with respect to each of the two factors; pn and p22 are cur- • the low value: -1
vature terms; and p12 is the interaction term. • the middle value: 0
The interaction term p12 is a measure of how much the • the high value: +1
• the highest value: +a
slope, with respect to one factor, changes as the other fac-
tor increases or decreases (5, 6). The full second-order poly-
nomial model usually provides a good approximation of the Coded Central Composite Design for a system
true behavior of a given system over a modest factor do- with two factors (k = 2).
main (2, 5, 7).
Design Point Factor *1 Factor *2
Interpretation of Terms in the Model
+ 1 +1
Figures 1-3 show that changes in the p0 term cause +1 -1
-1 +1
changes in the intercept (the response at zero X, and zero
-1 -1
x2). Likewise, as the magnitude of the curvature terms (pn
and p22) increases and decreases, the parabolic shape of 0 0
the response surface increases and decreases. When the +1.41 0
-1.41 0
signs of Pn and p22 are both negative, the parabola opens 0 +1.41
downward (Fig. 1); when the signs of pn and p22 are both
_Q_ -1.41
positive, the parabola opens upward (Fig. 2).

Volume 69 Number 7 July 1992 561

 The uncoded values may be calculated from the following
relationship.
*Ii=c1 + d1*;i (2)

where Xu is the uncoded value, x\i is the coded value, Ci is

the center point value expressed in real units, and d i is the
length expressed in real units between the center point
and the +1 value of the factor. The values ofci and di must
be such that the experimental design lies within any real
boundaries.
Although the central composite design specifies only
nine factor combinations, three additional center-point
replicates are usually performed to determine the repro-
ducibility of the system. Regression-analysis computer
programs using matrix least squares are available for cal-
culating the 3 values (the parameters). Details on matrix
least squares can be found in the literature (2, 3, 6, 12-15).

Experimental
To demonstrate the use of a central composite design, the
absorbance response from a constant volume of a solution
of vanadyl sulfate (VOSO4) can be investigated as a func-
tion of the volume in drops of hydrogen peroxide (H202)
and sulfuric acid (H2S04) that are added (16, 17). Figure 5. Graph of the fitted full two-factor second-order polynomial
The first factor xj is the number of drops of 1% H202. The model, eq 4.
second factor x2 is the number of drops of 20% H2S04. The
measured responseyq is the absorbance. The experimental
factor space can be bounded between 0 drops and 30 drops yl = 334.75 -

31.84*1 -

11.46x1 + 13.13(x*i)2
of H202 and H2S04.
+ 3.63(x2)2 + 24.50x4x2 (3)
When using c4 = 15, di = 5, and eq 2, the following equa-
tions give the real (uncoded) values chosen for both factors. The following is the fitted model in uncoded factor space
lowest (-a) = 8 in real units.

low (-1) = 10 y4 = 835.90 -

36.82*! -

21.34x2 + 0.53(*i)2

middle (0) = 15 + 0.15(x2)2 + 0.98* ix2 (4)

high (+1) = 20 A graph of the fitted full second-order polynomial model

22
highest (+a) =
Procedure
Add dropwise the amounts of 1% H202 and 20% H2S04,
in that order, that are specified by the experimental design
to 40 drops of a stock VOS04 solution (about 0.1 g dissolved
in 250 mL of distilled water). Stir the resulting mixture,
and allow it to equilibrate for 5 min after the addition of
H2S04.
Then measure the percent transmittance at 460 nm
using a visible spectrophotometer (e.g., Bausch & Lomb
Spectronic 20). Calculate the absorbance. The procedure is
a modification of a vanadium spot test used in inorganic
analysis (16, 17).
Results
Figure 4 shows the numerical results of the central com-
posite design. This design is moderately large and lies in
the center of the bounded factor domain. The absorbance
obtained from each of these experiments (xlOOO) is indi-
cated at each vertex. Four replicate measurements were
carried out at the center point.
It is possible to “let the data speak to us”. A strong inter-
action between the number of drops of H2S04 and the num-
ber of drops of H202 can be seen in Figure 4. At low levels
of H202, increasing the amount of H2S04 causes the
absorbance to decrease. However, at high levels of H202,
increasing the amount of H2S04 causes the absorbance re-
sponse to increase.
Regression analysis gives the fitted model in coded factor
space.
(Fig. 5) gives a geometric view of the shape of the esti-
mated response surface.
Additional Experiments
Equation 4 (Fig. 5) adequately describes the observed
data over the range of experimentation. However, students
might speculate about the observed decrease in absorb-
ance as the amounts of H202 and H2S04 are increased from
5 to 20 drops each. Is this a simple dilution effect caused by
the increased total volume?
While eq 4 might adequately describe the observed data
over the range of experimentation, does it extrapolate very
well into unexplored regions? Students should wonder, for
example, why the fitted model (Fig. 5) predicts a high
absorbance at 0 drops of H202 and 0 drops of H2S04. Does
this prediction make chemical sense? Would there really
be a high absorbance if an experiment were carried out at
0 drops of H202 and 0 drops of H2S04? An experiment
should be carried out there to confirm or deny any hypoth-
esis.
Similarly, does the predicted increased absorbance at 30
drops of H202 and 30 drops of H2S04 make chemical sense?
An additional experiment should be carried out at 30 drops
of each reagent to confirm or deny any hypothesis.
Conclusion
The quality of information obtained from multifactor ex-
perimental designs, such as the central composite design,
gives the researcher a broader understanding of the chem-
ical system being investigated. It also gives a richer basis
for asking further questions about the behavior of the sys-
tem (18).

562 Journal of Chemical Education

 6. Draper, N. R.; Smith, H. Applied Regression Analysis, 2nd ed.; Wiley: New York,
Acknowledgment 1981.
This work was supported by Grant No. 003652-108 from 7. Hartley, H. O. Biometrics 1959,15, 611-624.
8. Box, G. E. P; Wilson, K. B. J. Royal Stat. Soc. 1951, 13, 1-45.
the Advanced Technology Program, Texas Higher Educa- 9. Rubin, 1. B.; Mitchell, T. J.; Goldstein, G. Anal. Chem. 1971,43, 717-724.
tion Coordinating Board, Division of Research Programs. 10. Read, D. R. Biometrics 1954,10,1-13.
11. Bayne, C. K.; Rubin, I. B. Practical Experimental Designs and Optimization Methods
Literature Cited for Chemists] VCH: Florida, 1986.
12. Deming, S. N.; Morgan, S. L. Clin. Chem. 1979, 25, 840-855.
1. Box, G. E. Biometrics 1954, 10, 16-60.
P.
13. Deming, S. N. CHEMTECH 1989, 19, 249-255.
2. Deming, S. N.; Morgan, S. L. Experimental Design: A Chemo metric Approach.] Elsev-
ier: Amsterdam, 1987. 14. Deming, S. N. CHEMTECH 1989, 19, 504-511.
15. Deming, S. N. CHEMTECH 1990, 20, 118-126.
3. Deming, S. N. CHEMTECH 1989,19, 52-58.
4. Khuri, A. I.; Cornell, J. A. Response Surfaces: Designs and Analyses] Dekker: New 16. Feigl, F.; Anger, V. Spot Tests in Inorganic Analysis, 6th ed.; Elsevier: New York,
York, 1987. 1972.
5. Box, G. E. P; Hunter, W. G.; Hunter, J. S. Statistics for Experimenters: An Introduc- 17. Shavers, C. L.; Parsons, M. L.; Deming, S. N. J. Chem. Educ. 1979, 56, 307-309.
tion to Design, Data Analysis, and Model Building] Wiley: New York, 1978. 18. Strange, R. S. J. Chem. Educ. 1990, 67,113-115.

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