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DESIGN OF EXPERIMENT
 INTRODUCTION
 TERMINOLOGIES
 TYPES
 STEPS INVOLVED
 CASE STUDY

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Design of experiment is a strategy for setting up a set of experiments
in which all variables are varied in systematic manner , for the
purpose of determining the relation between variables and factors
to predict result.

Design of Experiments (DOE) also referred to as Experimental Design,

is the study of planning efficient and systematic collection of
responses from experimental units

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To Isolate the response of each input variable.

To determine responses of interactions.

To determine magnitude of experimental error

To obtain maximum information for given effort

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 To establish a causal link between selected
independent variables X’s and particular dependent
Y variables

 To isolate the independent variable being exerted

on a response variable

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 The major advantage of using design of experiment
to develop formulations for pharmaceutical products
is that it allows all potential factors to be evaluated
simultaneously , systematically and quickly.
 Using design of experiment one can evaluate the
effect of each formulation factor on each response
and identify the critical factors based on statistical
analysis .

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 Once the critical factors have been identified the
optimal formulation can be defined by using
proper design of experiment to optimize the levels
of all critical factors.

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1)Independent Variable/Factor:

Independent variables are the variables that can be

controlled. These variables are the parameters of the
experiment that are changed in order to see different
results.
2)Dependant variable / Response:

 Dependant variables can not be controlled directly since

they depend on the chosen independent variables.
They are measured to get the results of experiment .

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3) Coding Factor Levels : Transforming the scale of
measurement for a factor so that the high value
becomes +1 and the low value becomes -1.

4)Design : A set of experimental runs which allows to fit a

particular model and estimate the desired effect.

5)Treatment : A treatment is a specific combination of

factor levels whose effect is to be compared with other
treatments.

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6) Balanced Design: An experimental design where all cells
(i.e. treatment combinations) have the same number of
observations.
7) Blocking: A schedule for conducting treatment combinations
in an experimental study such that any effects on the
experimental results due to a known change in raw
materials, operators, machines, etc., become concentrated in
the levels of the blocking variable.
8) Confounding: A confounding design is one where some
treatment effects (main or interactions) are estimated by the
same linear combination of the experimental observations as
some blocking effects.

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9) Interactions: Occurs when the effect of one factor on
a response depends on the level of another factor(s).
10)Replication : Performing the same treatment
combination more than once .
11)Model: Mathematical relationship which relates
changes in a given response to changes in one or more
factors.
12)Level : A specific value of a factor that we will test

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 ONE FACTOR DESIGN

 FULL FACTORIAL DESIGN

 FRACTIONAL FACTORIAL DESIGN

 RESPONSE SURFACE DESIGN

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 SPACE FILLING DESIGN

 NON LINEAR DESIGN

 AUGMENTED DESIGN

 SIMPLEX DESIGN

 MIXED DESIGN

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1) Select problem
2) Determine dependant variables
3) Determine independent variables
4) Determine the no of levels of independent variables
5) Determine the possible combinations
6) Determine the no. of observations

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7) Redesign (if necessary)
8) Randomization
9) Mathematical model
10) Data processing
11) Data validation

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 Factorial design is an experiment in which the effects of
multiple factors are investigated simultaneously.

 The treatments consist of all combinations that can be

formed from the different factors.

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 You choose 2 or more factors to test
 You choose 2 or more levels for each factor
 You measure the response using various combinations of
factors and levels
 You determine which factors have the largest effects on
the response, and whether there are interactions
between factors

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 An experiment may be designed to focus attention on a
single independent variable or factor.
 An alternative approach is to study the influence of one
independent variable in conjunction with variations in
one or more additional independent variables.
 We can study not only the effects of the two
independent variables separately but also how they
combine to influence the dependent variable.

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 If the number of combinations in a full factorial design is
too high to be logistically feasible, a fractional factorial
design may be done, in which some of the possible
combinations (usually at least half) are omitted.
 A full factorial design contains all possible combinations
of low/high levels for all the factors. A fractional factorial
design contains a carefully chosen subset of these
combinations.

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 In factorial designs, each factor is assigned two levels.
These are typically called the low and high levels. For
computational purposes, the factors are scaled so that
the low level is assigned a value of -1 and the high level
is assigned a value of +1. These are also commonly
referred to as "-" and "+".

 In case of 2k factorial design

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 Number of Runs for a 2k Full Factorial
Number of Factors Number of Runs
2 4
3 8
4 16
5 32
6 64
7 128

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when the number of factors is 5 or greater, a full factorial design requires
a large number of runs and is not very efficient. A fractional factorial
design or a Plackett - Burman design is a better choice for 5 or more
factors.

In case of Two-level full factorial designs

Consider the two-level, full factorial design for three factors, namely the
23 design. This implies eight runs (not counting replications or center
point runs). Graphically, we can represent the 23 design by the cube
shown in Figure 3.1. The arrows show the direction of increase of the
factors. The numbers `1' through `8' at the corners of the design box
reference the `Standard Order' of runs

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In tabular form, this design is given by:

A 23 two-level, full factorial design table

showing runs in `Standard Order'

run X1 X2 X3

1 -1 -1 -1
2 1 -1 -1
3 -1 1 -1
4 1 1 -1
5 -1 -1 1
6 1 -1 1
7 -1 1 1
8 1 1 1

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 The main drawback of full factorial design is that the
number of experiments increases exponentially with the
number of factors .
 For example , for 6 factors 64 experiments are required
and for 7 factors as much as 128.
 Performing that many experiments in practice is not
feasible .Therefore often only fraction of full factorial
design is performed which is called as fractional factorial
design.

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 Fractional factorial designs are experimental designs
consisting of a carefully chosen subset (fraction) of the
experimental runs of a full factorial design.

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 Advantages of DOE
1. Design of experiment eliminates the ‘ confounding of
effects ’ whereby the effects of design variables are
mixed up. Confounding of effects means we can’t
correlate product changes with product characteristics.

2. Design of experiment helps us handle experimental

error.

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3. It helps us to determine the important variables that
need to be controlled.

4. It helps us to find the unimportant variables that

may not need to be controlled.

5. It helps us to measure interactions, which is very

important

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OPTIMIZATION OF MOUTH DISSOLVING TABLETS
OF TRAMADOL-Madgulkar et al (2008)

Objective: To prepare mouth dissolving tablets of

tramadol showing faster disintegration and good
mechanical strength (low friability).
Experimental Design: 32 Factorial Design
Factors : 1) Superdisintegrant (Crospovidone)
2) Mouth Melting Binder
(Gelucire 39/01)
Responses : 1) Disintegrating Time
2) Friability

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Coded factors Levels Factor

Crospovidone Gelucire 39/01

(% w/w) (% w/w)
-1 Low 3 4

0 Intermediate 6 6

1 High 9 8

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Formulation Coded Factor Level
Code
Factor 1 Factor 2

A1 -1 -1

A2 -1 0

A3 -1 1

A4 0 -1

A5 0 0

A6 0 1

A7 1 -1

A8 1 0

A9 1 1

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Ingredient Formulation Code

A1 A2 A3 A4 A5 A6 A7 A8 A9

DRC 103.9 103.9 103.9 103.9 103.9 103.9 103.9 103.9 103.9

Crospovidone 7.5 7.5 7.5 15 15 15 22.5 22.5 22.5

Gelucire 39/01 10 15 20 10 15 20 10 15 20

Citric acid 10.5 10.5 10.5 10.5 10.5 10.5 10.5 10.5 10.5

Sodium saccharin 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5

Menthol 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0

Orange flavour 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5

Aerosil 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.5

Mannitol 110.6 105.6 100.6 103.1 98.1 93.1 95.6 90.6 85.6

Total 250 250 250 250 250 250 250 250 250

All quantities in mg
DRC- Drug Resin Complex
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Formulation Disintegration Friability ± SD%
code Time (s) ± SD
A1 54±1.02 1.02±0.02
A2 48±0.89 0.88±0.01
A3 42±1.21 0.8±0.04
A4 36±0.67 0.73±0.02
A5 30±0.96 0.66±0.03
A6 25±0.82 0.60±00.02
A7 21±0.69 0.54±0.01
A8 16±0.77 0.48±0.03
A9 12±0.81 0.41±0.01
Broad range 12-54 0.41-1.02

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12)Madgulkar AR, Shelake MR, Padalkar AR. Formulation
design & potimization of novel taste masked mouth
dissloving tablets of tramadol having adequate
mechanical strength, APPS pharma sci. tech.,
2009:10(2):574-81
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,Oxford(1992)p.148.

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