computer aided formulation and development(How to use design expert software)
Mr. Roshan G Bodhe
M. Pharm Sem II
Department of Pharmaceutics
R.C.PATEL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH
• Why Necessary
• Term Used
• Optimization Parameter
• Problem Type
• Design Of Experiment
Formulation and development is a process of selection of component and
Now days computer tools used in the formulation and development of
Various technique, such as design of experiment are implemented for optimization
of formulation and processing parameter.
Traditionally optimization in pharmaceuticals refer changing one variable at a one
time, so to obtain solution of a problematic formulation.
Many times finding the correct answer is not simple and straight forward in such
cases use of computer tools (optimization procedure) for best compromise is the
smarter way to solve problem.
Optimization And Its Term
Optimization means:- Optimization means choosing the best element from
some set of available alternatives.
Factor:- It is an assigned & independent variables ,Such as temperature
and concentration. Those are quantitative & qualitative.
Level:-Those are designation assigned to the factor. Level indicated as
high, low, medium , Eg :-polymer ratios.
Response:-It is an outcome of an experiment. Eg:- Disintegration time
Response surface:-Response surface representing a relationship between
the independent variables X1&X2 and dependent variables Y.
Variables During Formulation
INDEPENDENT VARIABLES DEPENDENT VARIABLES
X1 Diluent Ratio Y1 Disintegration time
X2 Compression Force Y2 Hardness
X3 Disintegrant Level Y3 Dissolution
X4 Binder Level Y4 Friability
X5 Lubricant Level Weight uniformity
Design Of Experiment
Design of experiment :- Is a structure organized method used to
determine the factor affecting to process and output of that process.
some of factor are important ,while other factor are not important.
Few variables are effective or other are not effective.
Experimental design is an integral part of optimization technique.
Those technique used in the formulation optimization.
Design of Experiment For Formulation And
All pharmaceutical products are formulated to specific dosage form drugs to be
effectively delivered to patient typical pharmaceutical dosage form include
tablets, capsules, solution suspension, etc.
Different dosage form required different technology usually present different
technological challenge for formulation & development .
Due to complex challenges, formulations scientist used effective methodology
like as design of experiment and statistical analysis for formulation and
Formulation scientist used this method for process optimization and process
Software Silent feature
Design Expert Powerful & compressive package used for optimizing
pharmaceutical formulation and process
Minitab Powerful DOE software for automated data analysis MS-
Excel compatibility. Include almost all design of RSM.
DOE PRO XL MS-Excel compatible DOE software for automated data
CARD Powerful DOE software for data analysis include graphics
and help feature
How to used design Expert software version 7.0
How to install design expert software
1 install the exe file
2 Do not run design expert now
3 Copy the crack from crack folder to C/ program file / DX 7 trail run
4 If you want help then press F1for help
SOP of Design Expert Software
1) File new design
2) Click response surface
3) Add numeric factor
4) write name of independent variables
5) Add low limit and high limit
7) Add response
8) Run will be generated
Applying DOE to Formulation And Development
Factor Low Level
Diluent ratio 10 15 Disintegration time
Disintegrant level 5 10 Dissolution
Binder level 4 6 Friability
Lubricant level 6 8 Weight uniformity
Major Technical Challenges In Tablet Formulation
Development & Role Of DOE
Major challenge Potential process Technologies
Uniformity Fluid Bed Granulation
Compatibility Highly Compressible excipient
Flow ability Free Flowing excipients
Dissolution Tablet Matrix containing polymer
Common Formulation Factor For The Tablet And
Applicable Design of Experiment
Factor Response DOE approaches
%API Uniformity Factorial
% Binder Compactibility Fractional factorial
%Disintegrant Flowability Central composite
%Glidant Dissolution Central composite mixture
%Lubricant Stability Box -Behnken
STEP IN FORMULATION AND DEVELOPMENT
1) EXCIPIENT COMPABILITY-
First step in formulation and development is campactability study
those select the excipient .
Those are physically and chemically compatible with the API
It should be biodegradable and compatible
By applying doe we can understand interaction effect with API over a
By applying DOE we can understand the interaction effect of excipient
with API .
Excipient are selected from excipient compability study ,and next step is the
Those conducted to determine the manufacturing process that enable the
formulation to achieve TPP
Those evaluated technical challenges associated with the formulation and
In table no. 1 potential process are given to overcome the challenges in formulation
As technical challenges overcome the next step is selection of manufacturing
Selection Of Manufacturing Process
1)Formulation preliminary study:-
Those gives idea about selection of final excipient
2)Formulation optimization study:-
Those define the optimum level of excipient in the each formulation.
During this many formulation factor and response are evaluated in tablet
formulation and development. table 3
These problem can be solve by applying doe.
Those gives idea to understand formulation system and optimize the
formulation by choosing best combination of excipient to achieve the TPP
Initial Formulation System for Tablet Formulation
FACTOR API LEVEL & EXCIPIENT CHOICE
DILUENT MICROCRYSTALINE CELLULOSE
DISINTEGRANT SODIUM STARCH GLYCOLATE
LUBRICANT MAGNECIUM STEARATE
Design And Conduct a Formulation Optimization Study
FACTOR EXCIPIENT LOW SRENGTH
API - 5 10
Diluent MCC 59 30
Disintegrant Crospovidone 5 5
VARIABLES NO. OF LEVELS
All possible combination for excipient in the initial formulation
study are evaluated, a full factorial DOE is required 24 study.
As shown in below table
Design of experiment & statistical analysis have been used in the
Using design of experiment formulation scientist evaluate the all
formulation factors in systematically and timely manner to optimize the
formulation and manufacturing process
When the pharmaceutical process and product are optimize by systematic
approach then process validation & scale up can be efficient because of the
robustness of the formulation and manufacturing process
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