Professional Documents
Culture Documents
0t Mano
0t Mano
PHARMACEUTICAL
FORMULATION AND PROCESSING
Manoj R
1 Mpharm 1st semester
Department of pharmaceutics
Nandha College of pharmacy
Erode
09/09/2023
2 CONTENTS:
Introduction
Importance
Concept of optimization
Terms
Parameters
Experimental design
Techniques
Reference
09/09/2023
INTRODUCTION :
3
09/09/2023
4 FLOW CHART OF
OPTIMIZATION
09/09/2023
IMPORTANCE OF OPTIMIZATION
5
Primary objective may not be optimize absolutely but to compromise effectively &
thereby produce the best formulation under a given set of restrictions .
Innovation and
Reproducibility
efficacy
09/09/2023
6 Concept of Optimization
• Optimization is defined as “The process of finding the best values for the variables
of a particular problem to minimize or maximize an objective function.”
Concept of optimization
Black box
Uncontrollable Inputs
(Different Machines and different operators) 09/09/2023
7
It is used in pharmacy relative formulation and processing
Final product not only meets the requirements from the bioavailability but also
from the practical mass production criteria.
09/09/2023
Optimization Parameters
8
Parameters
Unconstraine
Constrained Dependent Independent
d
Formulating Processing
09/09/2023
9 Problem types
Unconstrained
Constrained
Independent Variable
Dependent Variable
The dependent variables are the responses or the characteristics of the in-
process material or the resulting drug delivery system. These are a direct
result or any change in the formulation or process.
09/09/2023
Example:
11
diameter
• If greater the variables in a given system, then greater will be the
12 complicated job of optimization.
• But regardless of the number of variables, there will be relationship
between a given response and independent variables.
• Once we know this relationship for a given response, then will able to
define a response surface
09/09/2023
13 TERMS USED:
Concentration 1%, 2%
RESPONSE: It is an outcome of the experiment.
14
It is the effect to evaluate.
Ex: Disintegration time etc..,
09/09/2023
16 Types of experimental designs:
Completely randomized designs
Randomized block designs
Factorial designs:
* Full
* Fractional
Response surface designs:
* Central composite designs
* Box-Behnken designs
Contour designs
09/09/2023
17
Completely randomized Designs:
These designs compares the values of a
response variable based on different levels
of that primary factor.
The levels of the primary factor are
randomly assigned to the experimental
designs.
For example ,if there are 3 levels of the
primary factor with each level to be run 2
times then there are 6 factorial possible run
sequences. 09/09/2023
18
Randomized block designs:
General rule- block what is possible & randomize what is not possible.
09/09/2023
19 Factorial Design(FD):
Factorial experiment is an experiment whose design consist of two
or more factor each with different possible values or “levels”.
Factorial design applied in optimization techniques.
Types of FD:
TWO TYPES-
Full Factorial Design.
Fractional Factorial Design.
09/09/2023
20 Factorial Design Testing:
In chromatographic condition responses can be
Efficiency
Retention factor
Asymmetry
Retention time
Resolution
09/09/2023
21
Software Used:
09/09/2023
Advantages:
22
It’s easier to study the combined effect of two or more factors
simultaneously and analyze their interrelationships.
Has a wide range of factor combination are used.
Drawback:
Wasting of time and experimental material.
Increase in factor size leads to increase in block size which increase
the chance of error.
It’s complex when several factors are involved simultaneously.
09/09/2023
Full Factorial Design:
23
A design in which every setting of every factor appears with setting of every
other factor is full FD.
Simplest design to create, but extremely inefficient.
If there is x factor, each at y level, a full FD has yx.
Number of Runs(N) N=y˟
Where, y= number of levels; x= number of factors.
ex: 2³=8
3factors, 2 levels each
09/09/2023
24
It depends on INDEPENDENT VARIABLES for development of new
formulation.
It also depends LEVELS as well as CODING.
can be Quantitative (numerical number) or they are Qualitative.
09/09/2023
Two Levels Full FD:
25
2 factors: X₁ and X₂
2 levels: Low and High
Coding: (-1), (+1)
Homogenous fractional
Mixed level fractional
Box-Hunter
Plackett - Burman
Taguchi
Latin square
09/09/2023
Homogenous fractional:
28
Useful when large number of factors must be screened efficiently & all
variables have the same number of levels.
Box-hunter:
Fractional designs with factors of more than two levels can be specified as
09/09/2023
homogenous fractional or mixed level fractional
29 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.
Used to investigate n-1 variables in n experiments, proposing
experimental designs for more than seven factors.
09/09/2023
30
Taguchi:
It is similar to PBDs.
It allows estimation of main effects while minimizing variance.
Latin square:
They are special case of fractional factorial design where there is one treatment
factor of interest and two or more blocking factors
09/09/2023
31 Response surface designs
-Designed for fitting these types of models are known as response surface
designs.
the goal is to minimize defects and maximize yield.
Two most common designs generally used in this response surface modeling
are
Central composite designs
Box-Behnken designs
09/09/2023
32
Box-Wilson Central Composite Design
This type contains an embedded factorial or fractional factorial design with centre
points that is augmented with the group of ‘star points’.
These always contain twice as many star points as there are factors in the design.
The star points represent new extreme value (low & high) for each factor in the
design
To picture central composite design, it must be imagined that there are several
09/09/2023
33
Central composite designs are of three types:
09/09/2023
34
09/09/2023
35
Box-Behnken designs:
Box-Behnken designs use just three levels of each factor.
In this design the treatment combinations are at the midpoints of edges of the
process space and at the center. These designs are rotatable (or near rotatable)
and require 3 levels of each factor.
These designs for three factors with circled point appearing at the origin and
possibly repeated for several runs.
It’s alternative to CCD.
The design should be sufficient to fit a quadratic model , that justify equations
based on square term & products of factors.
Y=b0+b1x1+b2x2+b3x3+b4x1x2+b5x1x3+b6X2X3+b7X12 +b8X22+b9X32 09/09/2023
36
A Box-Behnken Design
09/09/2023
37
Contour designs:
Definition:
A Contour plot is a graphical representation of the relationships among three
numeric variables in two dimension.
Two variables are for X and Y axes, and a third variable Z is for contour levels.
A contour plot is a graphical technique for representing a 3 dimensional
surface by plotting constant z slice, called contours, on a 2D format. That is,
given a value for z, lines are drawn by connecting the (x, y) co-ordinates where
that z value occurs.
The contour plot is an alternative to a 3-D surface plot.
09/09/2023
38
This contour plot shows that the surface 3-D representation of Contour plot
is symmetric and peaks in the centre.
09/09/2023
39
The contour plots are formed by,
Vertical axis: Independent Variable 2
Horizontal axis: Independent Variable 1
Lines: Iso-response values.
09/09/2023
40 The dex contour plot is a specialized contour plot used in
the design of experiments. In particular, it is useful for full
and fractional designs.
09/09/2023
Application in formulation:
41
Contour plots helps in visualizing the response surface.
Contour plots are useful for establishing desirable response values and
operating conditions.
This plot shows how a response variable relates to two factors based on
a model equation.
Points that have the same response are connected to produce contour lines
of constant responses.
Such type of plots and experimental designs are used for used optimization
techniques in Pharmaceuticals formulation and processing.
09/09/2023
42
Other applications:
Formulation and Processing
Clinical Chemistry
Medicinal Chemistry
High Performance Liquid Chromatographic Analysis
Formulation of Culture Medium in Virological Studies
Study of Pharmacokinetic Parameters
09/09/2023
43
Optimization Technology:
Classical optimization
Statistical optimization
Applied optimization
09/09/2023
CLASSICAL OPTIMIZATION:
44
Y = f(X)
09/09/2023
When the relationship for the response Y is given as the function of two
45
independent variables, X1 and X2 ,
Y = f(X1, X2)
Graphically, there are contour plots on which the axes represents the two
independent variables, X1 and X2, and contours represents the response Y.
DRAWBACKS:
Limited applications
Problems that are too complex.
They do not involve more than two variables.
09/09/2023
46 STATISTICAL OPTIMIZATION
09/09/2023
47 There are two possible approaches for this
Theoretical approach- If theoretical equation is known, no
experimentation is necessary.
Empirical or experimental approach – With single or more independent
variables, formulator experiments at several levels.
Drawback:
Applicable only to the problems that are not too complex.
They do not involve more than two variables.
For more than two variables graphical representation is impossible
09/09/2023
48 APPLIED OPTIMIZATION
The effect on a real system of changing some input(some variable) is
observed directly at the output(one measures some property).
Considering the changes in input and effect on output, the optimization
techniques are categorized into five types:
1. Evolutionary operations
2. Simplex method
3. Lagrangian method
4. Search method
5. Canonical analysis
09/09/2023
49 REFERENCE:
THANK YOU
09/09/2023