Introduction

 The term optimize is defined as to make, effective, or as functional as possible.

 Optimization is the process of finding the best way of using the existing resources while
taking in the amount of all the factors that influences decisions in any experiment
 Traditionally, Optimization in Pharmaceuticals refer to changing one variable at a time,
so to obtain solution of a problematic formulation.
 Modern Pharmaceutical optimization involves systematic design of experiments to
improve formulation irregularities.

Why optimization is necessary ?

 Reducing cost
 Safety and Reducing error
 Reproducibility
 Save time
 Optimization Parameters

Optimization
Parameters

Problem Variable
Type Type

Constrained Unconstrained Independent Dependent

 PROBLEM TYPES

UNCONSTRAINED CONSTRAINED

In un constrained there are Constraints are restrictions

no restrictions placed on the placed on a system by physical
system. limitations or by simple
practicality

For example- for a given For a given pharmaceutical system

pharmaceutical system one one has to make the hardest tablet
has to make the hardest possible which disintegrates in
tablet possible. about 15 minutes within the system.
 Variable type

Independent Dependent

The independent variables The dependent variables

are under the control of are the responses or the
the formulator. These characteristics that are
might include the developed due to the
compression force or the independent variables.
die cavity filling or the
mixing time etc.
Factors:
The independent variables, which influence the formulation characteristics or output of the
process, are labeled as factors. For example temperature, concenteration.

Levels:
The values assigned to the factors are termed as levels, e.g., 30°and 50°are the levels for the
factor - temperature.

Constraints:
The restrictions placed on the factor levels are known as constraints.

Dependent variables:
The characteristics of the finished drug product or the in-process material are known as dependent
variables,  e.g., drug release profile, friability, size of tablet granules, disintegration time, etc. 
Respones:
It is an outcome of result. For examples – Disintegration time and Dissolution time etc

Coding: when a variables has to be changed into non dimensional coded variable, this is
known as coding. Process of transformation.

Experimental design: Design of Experiments ( DoE ) is formal mathematical method for

systematically planning and conducting scientific studies that change experimental variables
together in order to determine their effect of a given response. It explains how the process go on
? The design used for the experiment will give precise information with minimal
experimentation. The design type of experiment depends on the model and objective of study.
Experimental designs are based on the randomization principles, replication principle and error
control principle.
Response surface: various types of data is obtained after DoE which represents the
interaction between independent variable and dependent variable. Response surface is
Graphical representation of obtained data.
Types of graph plots
1. Response surface plot: 3D format graph is obtained between 2 independent variables
and one response variable.
2. Contour plot: Graph between one independent variable against others. It is 2D
representation of a 3D response.

Mathematical models: simple algebraic equation representing the relationship

among different variables.
Types
3. Empirical: These are linear models.
4. Theoretical: These are non linear models.
 Optimization process

Real
Input Output
system

Input Mathematical
Response
factor level model of system

Optimization
procedure
Types of experimental design

 Completely randomized designs

 Randomized block designs
 Factorial designs
• Full factorial
• Fractional factorial
 Response surface designs
• Central composite designs
• Box Behnken designs
 Adding centre points
 Three level full factorial design
Completely randomized designs
It compare the values of response variable based on different level of that primary factor.
For example- If there are 3 levels of the primary factor with each level to be run 2 times the there 6
factorial possible run sequences.

Randomized Block designs

In this type, there is one factor or variable that is of primary interest. Technique used to reduce or
eliminate experimental error is called blocking which also control non significant factors.
Factorial Designs
These are the design of choice for simultaneous determination of the
effects of several factors and there interaction
Symbols to denote levels are : when both the variables are in low
concentration.
• One low variable and second high variable
• One high variable and second low variable
• Both variable are high
Factorial designs are optimal to determine the effect of pressure and
lubricant on the hardness of a tablet Effect of disintegrant and lubricant
concentration on tablet dissolution. It is based on therou of probability and
test of significance.
Response surface designs

A response surface design is a set of advanced design of experiments (DOE)

techniques that help you better understand and optimize your response.
Response surface design methodology is often used to refine models after you
have determined important factors using screening designs or factorial designs;
especially if you suspect curvature in the response surface.

Response surface with no curvature Response surface with curvature

The difference between a response surface equation and the equation for a factorial
design is the addition of the squared (or quadratic) terms that lets you model
curvature in the response, making them useful for:
•Understanding or mapping a region of a response surface.
•Response surface equations model how changes in variables affect a response of
interest.
•Finding the levels of variables that optimize a response.
•Selecting the operating conditions to meet specifications.

For example, you would like to determine the best conditions for injection-molding a
plastic part. You first used a screening or factorial experiment to determine the
significant factors (temperature, pressure, cooling rate). You can use a response
surface designed experiment to determine the optimal settings for each factor.
There are two main types of response surface designs:
Three level full factorial designs

It is written as 3k factorial design. It means that k factors are considered each at 3 levels. These
are usually referred to as low intermediate and high values. These values are usually expression
0, 1, and 2. The third level for a continuous factor facilitates investigation of a quadratic relaton