Concept of Optimization,

Optimization Parameters and

Factorial Design

By: Sonai Tarei

Mpharm II Sem.

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 Optimization Concept:
 The term Optimize is defined as to make perfect , effective
, or as functional as possible.

 It is the process of finding the best way of using the

existing resources while taking in to the account of all the
factors that influences decisions in any experiment

 Modern pharmaceutical optimization involves

systematic design of
experiments (DoE) to improve formulation irregularities.

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 Optimization is used in pharmacy relative to
formulation and processing .
.
In development projects , one generally
experiments by a series of logical steps, carefully
controlling the variables & changing one at a
time, until a satisfactory system is obtained

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 Target processing parameters – ranges for each
excipients & processing factors .

Questions optimization requires:

• How we can make Formulation perfect ?

What should be characteristics?
What should be the conditions?

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Why is Optimization necessary?
Primary objective may not be to optimize absolutely but to compromise
effectively & thereby produce the best formulation under a given set of
restrictions .

Reducing
cost

Safety &
Save OPTIMIZATION Reducing
Time
error

Reproducib
ility

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 APPLICATIONS:

Formulation and Processing

Clinical Chemistry

Medicinal Chemistry

High Performance Liquid Chromatographic

Analysis

Formulation of Culture Medium in Virological

Studies.

Study of Pharmacokinetic Parameters.

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Terms Used
o FACTOR: It is an assigned variable such as concentration , Temperature
etc..,
• Quantitative: Numerical factor assigned to it
Ex- Concentration- 1%, 2%,3% etc.
• Qualitative: Which are not numerical
Ex- Polymer grade, humidity condition etc.
o LEVELS: Levels of a factor are the values or designations assigned to
the factor.
o RESPONSE: It is an outcome of the experiment.
• It is the effect to evaluate.
Ex- Disintegration time.

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 Terms Used
o EFFECT: It is the change in response caused by
varying the levels
 It gives the relationship between various factors
& levels.

o INTERACTION: It gives the overall effect of two

or more variables
Ex- Combined effect of lubricant and glidant on
hardness of the tablet

FACTOR LEVELS

Temperature 300 , 500

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Concentration 1%, 2% 05-04-2018
Advantages
o Yield the “Best Solution” within the domain of study.

o Require fewer experiments to achieve an

optimum formulation.

o Can trace and rectify problem in a remarkably easier

manner.

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 Softwares for Optimization
Design Expert 7.1.3
SYSTAT Sigma Stat 3.11
CYTEL East 3.1
Minitab
Matrex
Omega
Compact 21-Apr-15 O

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 Optimization Parameters

CONSTRAINED

PROBLEM TYPE

UNCONSTRAINED
PARAMETERS

VARIABLES DEPENDENT

INDEPENDENT
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 Problem Types
Unconstrained
• In unconstrained optimization problems there are no restrictions.

• For a given pharmaceutical system one might wish to make the hardest

tablet possible.

• The making of the hardest tablet is the unconstrained optimization problem.

Constrained
• The constrained problem involved in it, is to make the hardest tablet possible,

but it must disintegrate in less than 15 minutes.

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 Variables
• Independent variables : The independent variables are under the control of
the formulator. These might include the compression force or the die cavity

filling or the mixingtime.

• Dependent variables : The dependent variables are the responses or the

characteristics that are developed due to the independent variables. The

more the variables that are present in the system the more the

complications that are involved in theoptimization.

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 Example of Variables

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 Once the relationship between the variable
and the response is known, it gives the
response surface as represented in the Fig. 1.
Surface is to be evaluated to get the
independent variables, X1 and X2, which
gave the response, Y. Any number of
variables can be considered, it is impossible
to represent graphically, but mathematically it
can be evaluated.

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 Factorial Design (FD)
Factorial experiment is an experiment whose
design consist of two or more factor each with
different possible values or “levels”.
FD technique introduced by “Fisher” in 1926.
Factorial design applied in optimization
techniques.

Factors : Factors can be “Quantitative” (numerical

number) or they are qualitative. They may be
names rather than numbers like Method 1, site B,
or present or absent .
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 Factorial design depends on independent
variables for development of new formulation .
Factorial design also depends on Levels as well
as Coding
There are three types of levels : 1) LOW
2)INTERMEDIATE 3) HIGH
Simultaneously CODING takes place for Levels :
1) for LOW = (-1)
2)For intermediate = (0)
3) for HIGH =(+1)

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 FD is for the evaluation of multiple factors
simultaneously.
2 3 means 2 is level while 3 is factor .
Factorial Design is divided into two types
1. Full Factorial Design
2.Fractional factorial design

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 1.Full Factorial Design

A design in which every setting of every factor

appears with setting of every other factor is full
factorial design.
Simplest design to create, but extremely
inefficient.
If there is k factor , each at Z level , a Full FD has
ZK

Number of runs (N)

N = y x Where, y = number of levels, x = number of
factors E.g.- 3 factors, 2 levels each, N = 23 = 8
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 Factorial Design : 22 , 23 , 32 , 33
22 FD = 2 Factors , 2 Levels = 4 runs
23 FD = 3 Factors , 2 Levels = 8 runs
32 FD = 2 Factors , 3 Levels = 9 runs
33 FD = 3 factors , 3 Levels = 27 runs

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 TWO Levels Full FD :
2 factors : X1 and X2 (Independent variables)
2 levels : Low and High
Coding : (-1) , (+1)
Three level Full FD :
In three level factorial design ,
• 3 factors: X1, X2 and X3
• 3 levels are use ,
1) low (-1)
2) intermediate (0)
3) high (+1)

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Full Factorial Design : Design Matrix
Full Factorial Design : Result Matrix
Sample 23 Experiment

9+9+3+3 7+9+8+8
6 8

Main Effect of X1 6 – 8 = -2
 Why Fractional Factorials?

Full Factorials
No. of combinations

For
two-levels

Continuous development of Knowledge is

introducing more and more factors

In engineering, this is the sample

size -- no. of prototypes to be built.
 Some Basic
Definitions

Definition of a factor effect: The change in the mean response

when the factor is changed from low to high
40  52 20  30
A  y A  y A    21
2 2
B  y   y   30  52  20  40  11
B B
2 2
52  20 30  40
AB    1
2 2
Design & Analysis of 5
Experiments 8E 2012
The Case of
Interaction:

50 12 20  40

A  y A  y A  1
2 2
B  y   y   40 12  20  50  9
B B
2 2
12  20 40  50
AB    29
2 2
Design & Analysis of 6
Experiments 8E 2012
Regression Model & The Associated Response
Surface

y  0  1x1  2 x2  12 x1x2  

The least squares fit is
yˆ 35.5 10.5x1  5.5x2  0.5x1x2  35.5 10.5x1  5.5x2
The Effect of Interaction on the
Response Surface

Suppose that we add an interaction term to the model:

yˆ 35.5 10.5x1  5.5x2 8x1x2

Interaction is actually a form of curvature

 Why so many Treatments?

“There tends to be a redundancy in full factorial designs”

– redundancy in terms of an excess number of interactions that can be
estimated …
Fractional factorial designs exploit this redundancy …” 
philosophy
How to select a subset of 4 runs from a 23=8 -run
design?
Many possible “fractional” designs
First Choice
Second Choice
Third Choice

Wow!

Balanced design
All factors occur and low and high levels
same number of times; Same for interactions
Columns are orthogonal. Projections …
 Good statistical properties
Want to study 5 factors (1,2,3,4,5) using a 2^4 = 16-run design
i.e., construct half-fraction of a 2^5 design
= 2^{5-1} design
 FRACTIONAL FACTORIAL
DESIGN
In Full FD , as a number of factor or level
increases , the number of experiment required
exceeds to unmanageable levels .
In such cases , the number of experiments can
be reduced systemically and resulting design is
called as Fractional factorial design (FFD).
Applied if no. of factor are more than 5 .
Means “less than full”
Levels combinations are chosen to provide
sufficient information to determine the factor
effect
More efficient
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 Types of Fractional Factorial
Design
Homogeneous fractional
Mixed level fractional
Plackett-Burman
Homogenous fractional
Useful when large number of factors must be
screened
Mixed level fractional
Useful when variety of factors need to be
evaluated for main effects and higher level
interactions can be assumed to be negligible.

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 Plackett-Burman
It is a popular class of screening design.
These designs are very efficient screening
designs when only the main effects are of
interest.
These are useful for detecting large main effects
economically ,assuming all interactions are
negligible when compared with important main
effects

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 Thank you..

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