The term “optimize” is “to make as perfect”. It is defined as follows: choosing the best element from some set of variable alternatives.
An art ,process ,or methodology of making something (a design system or decision ) as perfect ,as functional, as effective as possible .
you can know about the central composite design, historical design, optimisation techniques and also about the TYPES OF CENTRAL COMPOSITE DESIGN, BOX-BEHNKEN DESIGN, DATA COLLECTION, CRITICISM OF DATA, PRESENTATION OF FACTS, PURPOSE, OPTIMISATION PROCESS, DIFFERENT TYPES PRESENT IN IT AND THEIR CLASSIFICATION AND EXPLANATION.
FDA’s emphasis on quality by design began with the recognition that increased testing does not improve product quality (this has long been recognized in other industries).In order for quality to increase, it must be built into the product. To do this requires understanding how formulation and manufacturing process variables influence product quality.Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
This presentation - Part VI in the series- deals with the concepts of Design of Experiments. This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
Introduction & Basics of DoE
Terminologies
Key steps in DOE
Softwares used for DOE
Factorial Designs ( Full and Fractional)
Mixture Designs
Response Surface Methodology
Central Composite Design
Box -Behnken Design
Conclusion
References
WHAT IS COMPRESSION ?
Compression means reduction of bulk volume of material as a result of the removal of gaseous phase (air) by applied pressure
WHAT IS CONSOLIDATION?
Consolidation is an increase in mechanical strength of material resulting from particle - particle interactions.
you can know about the central composite design, historical design, optimisation techniques and also about the TYPES OF CENTRAL COMPOSITE DESIGN, BOX-BEHNKEN DESIGN, DATA COLLECTION, CRITICISM OF DATA, PRESENTATION OF FACTS, PURPOSE, OPTIMISATION PROCESS, DIFFERENT TYPES PRESENT IN IT AND THEIR CLASSIFICATION AND EXPLANATION.
FDA’s emphasis on quality by design began with the recognition that increased testing does not improve product quality (this has long been recognized in other industries).In order for quality to increase, it must be built into the product. To do this requires understanding how formulation and manufacturing process variables influence product quality.Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
This presentation - Part VI in the series- deals with the concepts of Design of Experiments. This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
Introduction & Basics of DoE
Terminologies
Key steps in DOE
Softwares used for DOE
Factorial Designs ( Full and Fractional)
Mixture Designs
Response Surface Methodology
Central Composite Design
Box -Behnken Design
Conclusion
References
WHAT IS COMPRESSION ?
Compression means reduction of bulk volume of material as a result of the removal of gaseous phase (air) by applied pressure
WHAT IS CONSOLIDATION?
Consolidation is an increase in mechanical strength of material resulting from particle - particle interactions.
Optimization techniques and various method of optimization
Full Factorial Design
Introduction to Contour Plots
Introduction of Response Surface Design
Classification
Characteristics of Design
Matrix and analysis of design with case study
Equation of Full and Reduced mathematical models in experimental designs
Central Composite designs
Taguchi and mixtures designs
Application of experimental designs in pharmacology for reduction of animal
Similar to Optimization techniques in formulation Development Response surface methodology (20)
Human life is based upon the principle of work.
▪ One has to work to earn his livelihood.
▪ Pharmacy is one of the professions.
▪ The pharmacy council of India has introduced a new subject
named “Drug store and business management”.
▪ Syllabus is divided into two parts – part I commerce and part
II Accountancy.
▪ The purpose of this subject is to familiarise the students with
the basic concept of business, its proper management, sources
of finances in order to run it successfully and the last, the way
and means to note down various transactions in books of
account with a view to having a permanent record of the same.
Distribution is significant rated as a significant function of marketing. After
production a product moves to the market and finally to the consumer.
▪ This journey of the product from the manufacturer or producer to the consumer is
made possible through certain defined paths, termed as, “Channels of
Distribution”
Distribution is significant rated as a significant function of marketing. After
production a product moves to the market and finally to the consumer.
▪ This journey of the product from the manufacturer or producer to the consumer is
made possible through certain defined paths, termed as, “Channels of
Distribution”
Monoclonal antibodies are antibodies that have a high degree of specificity (mono-specificity) for an antigen or epitope. Monoclonal antibodies are typically derived from a clonal expansion of antibody producing malignant human plasma cells. The initial monoclonal antibodies were created by fusing spleen cells from an immunized mouse with human or mouse myeloma cells (malignant self-perpetuating antibody producing cells), and selecting out and cloning the hybrid cells (hybridomas) that produced the desired antibody reactivity. These initial monoclonal products were mouse antibodies and were very valuable in laboratory and animal research and diagnostic assays, but were problematic as therapeutic agents because of immune reactions to the foreign mouse protein. Subsequently, production of chimeric mouse-human monoclonal antibodies and means of further “humanizing” them and producing fully human recombinant monoclonal antibodies were developed.
Chapter-1 Introduction to Human Anatomy and PhysiologyD.R. Chandravanshi
Anatomy (Greek anatomē, 'dissection') is the branch of biology concerned with the study of the structure of organisms and their parts. Anatomy is a branch of natural science which deals with the structural organization of living things. It is an old science, having its beginnings in prehistoric times. Anatomy is inherently tied to developmental biology, embryology, comparative anatomy, evolutionary biology, and phylogeny, as these are the processes by which anatomy is generated, both over immediate and long-term timescales. Anatomy and physiology, which study the structure and function of organisms and their parts respectively, make a natural pair of related disciplines, and are often studied together. Human anatomy is one of the essential basic sciences that are applied in medicine.
Program among these measures are the NATIONAL HEALTH PROGRAMS, which have been launched by the central government of control/ eradication of communicable diseases, improvement of environmental sanitation, raising the standard of nutrition, control of population and improving rural health. Introduction
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is unique in bringing together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration. Since its inception in 1990, ICH has gradually evolved, to respond to the increasingly global face of drug development. ICH’s mission is to achieve greater harmonisation worldwide to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner. On 23 October 2015, ICH announced organisational changes as it marks 25 years of successful harmonisation.
Forms of business organization, DSBM D.Pharma 2nd yearD.R. Chandravanshi
The legal entity can be in any form of a business organization. The various forms of organization are as follows: 1) Sole proprietorship 2) Partnership 3) Co-operative Society 4) Joint stock company (Private and Public) These are explained in brief as follows:-3.1 OBJECTIVES At the end of this lesson you will be able to know z Various forms of organization z Its formation & features z Merits & Demerits
Psoriasis is an autoimmune condition that affects skin. It is characterized by changes in the skin that include hyperkeratosis, parakeratosis, and akantosis.
They are attributed to an increased mitosis rate in the basal region of the epidermis, as well as disorders of maturing and differentiating keratinocytes.
These changes in the dermis and epidermis cause the typical desquamation of the stratum corneum observed in psoriasis. The psoriatic lesions indicate an inflammatory reaction caused by the secretion of pro-inflammatory cytokines from macrophages, lymphocytes, and neutrophils.
These cytokines may stimulate the inflammatory response via the lipoxygenase and the cyclooxygenase (COX) pathways.
The red, scaling psoriatic plaques often itch and burn. People with psoriasis may suffer discomfort, including pain and itching and emotional distress Psoriasis affects 1% to 2% of the population.
Omega−3 fatty acids, also called Omega-3
oils, ω−3 fatty acids or n−3 fatty acids,
are polyunsaturated fatty acids (PUFAs)
characterized by the presence of a double
bond three atoms away from the terminal
methyl group in their chemical structure.
They are widely distributed in nature, being
important constituents of animal lipid
metabolism, and they play an important
role in the human diet and in human
physiology.
https://www.slideshare.net/DauRamChandravanshi1
Pilot Plant:-
“Defined as a part of pharmaceutical industry where a lab scale formula is transformed into viable product by the development of liable practical procedure for manufacture”.
Scale-up:-
“The art of designing of prototype using the data obtained from the pilot plant model”
Optimum performance laminar chromatography (OPLC) is a pumped flow chromatography techniques that combine the user – friendly interface of HPLC with the capacity of flash chromatography and multidimensionally of TLC .
Optimum performance laminar chromatography (OPLC ) , in a contrast , is a pumped flow chromatography system that uses a planar 2D column format .
The multidimensionally capacity of OPLC is not limited to the separation technique alone , but also to the multitude of sample application and detection methods that are available .
SYNTHETIC PEPTIDE VACCINES AND RECOMBINANT ANTIGEN VACCINED.R. Chandravanshi
What is a Vaccine?
A vaccine is a substance that is introduced into the body to prevent infection or to control disease due to a certain pathogen (a disease-causing organism, such as a virus, bacteria or parasite). The vaccine “teaches” the body how to defend itself against the pathogen by creating an immune response.
1 Unlike traditional pharmaceuticals, vaccines are biologics since they are made from living organisms (biological sources).
2 Specifically, vaccines are preparations of components derived from (or related to) a pathogen; they can typically induce a protective effect through one to three very small doses, in the range of micrograms to milligrams.
3 Immunity lasts for an extended period, from one year up to lifetime protection, including prevention of disease and/or related sequelae.
Synthetic peptide vaccines represent fragments of protein antigen sequences, synthesizing specific B cell and T cell epitopes offer the potential to induce diseases neutralizing immuno response with completely synthetic structure. Now it is well established that short chain peptides can be used to mimic antigenic sites of viruses and thus can be used the basics for vaccines and development. therefore, attempts have been made to synthesize such peptides which act as the serrogate immuunogens, as an alternative to the existing conventional vaccines.
vaccine is a biological preparation that provides active acquired immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future.
HISTORY OF VACCINES-
EDWARD JENNER conduct experiments in 1796 that lead to the creation of the first smallpox vaccine for prevention of smallpox.
A vaccine for RABIES is developed by LOUIS PASTEUR .
Vaccine for COLERA and TYPHOID were developed in 1896 and PLAGE vaccine in 1887.
The first DIPHTHERIA vaccine is developed in about 1913 by EMIL ADOLPH BEHRING,WILLIAM HALLOCK PARK.
The whole cell PERTUSIS vaccines are developed in 1914.
A TETANUS vaccine is developed in 1927.
Immunity
It can be defined as the resistance to disease, specifically to infectious disease or pathogens. The term “immune” is derived from the Latin word “immunis” that is exempt from charges. In medical term, it refers to the being protected from infectious pathogens.
Immune system
It is adaptive defense system which is able to generate a variety of cell and molecules capable of specifically recognizing and eliminating a variety of limitless foreign invaders into the system.
In 1975 Georges Kohler and Milstein succeeded in making fusions of myeloma cell lines with B cells to create hybridomas that could produce antibodies.
antibody
Also known as immunoglobulin is a large, Y shaped glycoprotein produced mainly by plasma cells that is used by the immune system to neutralize pathogens.
monoclonal antibodies
Antibodies that are made by identical immune cells that are clones of a unique parent cell.
polyclonal antibodies
A polyclonal antibodies represents a collection of antibodies from different B cells that recognize multiple epitopes on the same antigen.
A scanning electron microscope is a type of electron microscope that produces images of a sample by scanning the surface with a focused beam of electrons. The electrons interact with atoms in the sample, producing various signals that contain information about the sample's surface topography and composition.
SEMs can magnify an object from about 10 times up to 300,000 times. A scale bar is often provided on an SEM image. From this the actual size of structures in the image can be calculated.
Gas chromatography-mass spectrometry (GC-MS) is the synergistic combination of two analytical method to separate and identify different substances within a test sample.
Gas chromatography separates the components of a mixture in time.
Mass spectrometer provides information that aids in the identification and structural elucidation of each component.
These are the sterile preparation intended to administered other than intestinal route to bypass first pass metabolism and directly goes to systemic circulation.
These preparation give quick onset of action and site specific activity.
Suitable for drugs which are inactive in GIT environment.
Can be given unconscious or vomiting or diarrheal patient.
These are the sterile preparation intended to administered other than intestinal route to bypass first pass metabolism and directly goes to systemic circulation.
These preparation give quick onset of action and site specific activity.
Suitable for drugs which are inactive in GIT environment.
Can be given unconscious or vomiting or diarrheal patient.
Parenterals are the sterile preparation that is directly administered into the circulatory system avoiding the enteral route. And these preparation provide rapid onset of action that is why the administered preparation must be safe.
Stability problem arise from microbial contamination of these products so sterility and stability must be ensured for these preparations.
To ensure their sterility and stability, regulations regarding to quality control through pharmacopeial specifications has great importance.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Optimization techniques in formulation Development Response surface methodology
1. DEPARTMENT OF PHARMACEUTICAL SCIENCES
Dr. HARISINGH GOUR VISHWAVIDYALAYA, SAGAR (M.P.)
Presented By
Jaising Toppo
M.Pharma. 1st sem.
RESPONSE SURFACE METHODOLOGY
&
APPLICATION OF DESIGN OF EXPERIMENT
3. OBJECTIVES
To determine the variation.
To quantify response with respect to variables.
To find out the variables.
D.R. CHANDRAVANSHI
4. DEFINITION
The term “optimize” is “to make as perfect”. It is defined as follows:
choosing the best element from some set of variable alternatives.
An art ,process ,or methodology of making something (a design system
or decision ) as perfect ,as functional, as effective as possible .
D.R. CHANDRAVANSHI
5. INTRODUCTION
In development projects pharmacist generally experiments by a series
of logical steps ,carefully controlling the variables and changing one at a
time until satisfactory results are obtained .This is how the optimization
done in pharmaceutical industry .
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 the
decision in any experiment.
final products not only meets the requirements from the bioavailability
but also from the practical mass production criteria.
D.R. CHANDRAVANSHI
6. ADVANTAGES
Yield the “best solution” within the domain of study.
Require fewer experiments to achieve an optimum formulation.
Can trace the rectify “problem” in a remarkably easier manner.
D.R. CHANDRAVANSHI
8. PROBLEM TYPES IN OPTIMIZATION
PROBLEM TYPES IN
OPTIMIZATION
Unconstrained :no restrictions are
required
e.g. preparation of hardest
tablet without any
disintegration or dissolution
parameters
Constrained :restrictions
are placed on the system
e .g. preparation of
hardest tablet which has
the ability of disintegrate
in less than 15 min.
D.R. CHANDRAVANSHI
9. VARIABLES IN OPTIMIZATION
Variables in
optimization
Independent variables:
directly under the control of
formulator
e.g. disintegrant level
,compression force ,binder
level uniformity, lubricant
level, mixing time etc.
Dependent variables :
responses that are developed
due to the independent
variables
e.g. disintegration time,
hardness,weight,thickness etc.
D.R. CHANDRAVANSHI
10. PROBLEM TYPE PARAMETERS IN
OPTIMIZATION
Unconstrained:-In unconstrained optimization problem 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.
D.R. CHANDRAVANSHI
11. VARIABLES TYPE PARAMETERS IN
OPTIMIZATION
Independent variables:-The independent variable is under the control of
formulator .These might include the compression force or die cavity filing or
the mixing time ,diluents ratio,disintegrant level, binder level, lubricant level
etc.
Dependent variable:- These are the responses or the characteristics that
are develop due to the independent variables e.g. disintegration time
,hardness dissolution friability weight uniformity etc. The more the
variables that are present in the system the more complications that are
involved in the optimization.
Once the relationship between the variables and response is known, it
gives the response surface as represented in the next slide.Surface is to be
evaluated to get the independent variables , X1 & X2 which give the
response Y . Any number of variables can be considered it is impossible to
represent graphically , but mathematically it can be evaluated.
Y = f (X1,X2……) + e
D.R. CHANDRAVANSHI
12. Continue……..
Factor:- It is Assigned and Independent variables, which affect the
product or output of the process. It is an assigned quantitative and
qualitatively like this.
Quantitative: Numerical factor assigned to it. Ex; Concentration- 1%, 2%,
3% etc.
Qualitative: These are not numerical. Ex; Polymer grade, humidity
condition etc.
Level:- Levels of a factor are the values or designations assigned to the
factor.
Response surface:- Response surface representing the relationship
between the independent variables X1 and X2 and the dependent
variable Y.
Run or trials:- Experiments conducted according to the selected
experimental design
D.R. CHANDRAVANSHI
13. Continue……….
Contour Plot:- Geometric illustration of a response obtained by
plotting one independent variable against another, while holding the
magnitude of response and other variables as constant.
Interaction:- It gives the overall effect of two or more variables means
lack of additively of factor effects Ex: Combined effect of lubricant and
glidant on hardness of the tablets.
D.R. CHANDRAVANSHI
15. GRAPHICALLY REPRESENTATION OF RESPOSE
SURFACE METHOD
Figure : Response surface representating the relationship
between the independent variables X1 & X2 and the
response Y1
D.R. CHANDRAVANSHI
16. CLASSICAL OPTIMIZATION
Classical optimization is done by using the calculus to basic problem to
find the maximum and the minimum of the function.
The curve in the figure represents the relationship between the
response Y and the single independent variable X and we can obtain the
maximum and the minimum.By using the calculus the graphical
representation can be avoided. If the relationship ,the equation for Y as
a function X , is available .
Y = f(X) ……….eq1
When the relationship for the response Y is given as the function of two
independent variables , X1 & X2
Y = f(X1,X2) ……eq2
D.R. CHANDRAVANSHI
18. DRAWBACK OF CLASSICAL OPTIMIZATION
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 .
D.R. CHANDRAVANSHI
19. APPLIED OPTIMIZATION METHODS
1. Evolutionary operation
2. Sequential Simplex method
3. Lagrangian method
4. Search method
5. Canonical analysis
Evolutionary operations (EOVP):-It is a method of experimental
optimization. Small changes in the formulation or process are made (i.e.
repeat the experiment so many times) & statistically analyzed whether it is
improve .
It continues until no further changes take place i.e. it has reached
optimum the peak. The result of changes are statistically analyzed.
D.R. CHANDRAVANSHI
20. WHERE WE HAVE TO SELECT THIS
TECHNIQUE ?
This techniques especially well suited to a production situation.
The process is run in a way that is both produce a product that meets all specifications and
(at the same time ) generates information on product improvement.
Applied mostly to tablets.
Advantages:-
(1) Generates information product development .
(2) Predict the direction of improvement.
(3) Help formulates to decide optimum condition for the formulation and process.
Limitations :-
(1) More repetition is required .
(2) Time consuming .
(3) Not efficient to finding true optimization .
(4) Expensive to use.
D.R. CHANDRAVANSHI
21. Continue…….
Example:- Tablet
How can we get
hardness
By changing
the conc. Of
binder
Hardness Response
In this example, a formulator can changes the concentration of binder
and get the desired hardness.
D.R. CHANDRAVANSHI
22. SEQUENTIAL SIMPLEX METHOD
It is sequential because the experiments are analyzed one by one ,as each is
carried out .
This procedure may be used to determine the relative proportion of
ingredients that optimizes the formulation with respect to a specified
variables(s) or outcome.
A common problem in pharmaceutics occurs when the components of a
formulation are varied in an attempt to optimize its performance with
respect to such variables as drug solubility, dissolution time and hardness.
An approach is with example ,three components of the formulation will be
varied – stearic acid,satrch and declaim phosphate – with the restriction
that the sum of the total weight must equal 350 mg .The formulation can be
optimized for more than one attribute ,but for the sake of simplicity ,only
one effect dissolution rate,is considered.
D.R. CHANDRAVANSHI
23. Figure:-Special cubic simplex design for a three component mixture.
Each point represents a different formulation.SA=Stearic
acid;ST=Starch;DCP=Dicalcium phosphate.
D.R. CHANDRAVANSHI
24. Seven formulas to be tested –actual and (transformed) values
Transformed % = (actual% -minimum %)/(maximum % -minimum%)
D.R. CHANDRAVANSHI
25. Respose surface methodology
Response surface method (RSM) is a set of techniques used in the empirical study of
relationships .
RSM is a collection of mathematical and statistical techniques for empirical model
building, in which a response of interest is influenced by several variables and the
objective is to optimize this response .
RSM is useful in three different techniques or methods : (i) statistical experimental
design, in particular two level factorial or fractional factorial design, (ii) regression
modeling techniques, and (iii) optimization methods.
The most common applications of RSM are in Industrial, Biological and Clinical
Science, Social Science, Food Science, and Physical and Engineering Sciences.
D.R. CHANDRAVANSHI
26. Continue…….
The first goal for Response Surface Method is to find the optimum
response.
When there is more than one response then it is important to find the
compromise optimum that does not optimize only one response.
When there are constraints on the design data, then the experimental
design has to meet requirements of the constraints.
The second goal is to understand how the response changes in a given
direction by adjusting the design variables.
D.R. CHANDRAVANSHI
27. Continue….
The probabilistic analysis, an explicit or implicit functional relationship
between input parameters and output response is required, which is
normally difficult to establish except for simple cases and even the
established functional relationship is sometimes too complicated to
perform the conventional probabilistic analysis through integration or
through first or second order derivatives. In such circumstances,
authors propose to use the concept of response surface methodology
to establish an approximate explicit functional relationship between
input variables (x1, x2, x3 …) and output response (y) through
regression analysis for the range of expected variation in the input
parameters.
Y= f (x1, x2, x3…) + e
D.R. CHANDRAVANSHI
28. Continue……….
The essential steps in response-surface methodology are as follows:
1. The objective of the experiment is decided upon.
2. The important factors and their interactions are identified, perhaps
after a screening experiment. The levels of the factors which are to
be used are also established.
3. A possible mathematical model is selected.
4. An experimental design that is appropriate to the model is chosen.
5. The experiments are carried out, and the values of the factors and the
response fitted to the mathematical model.
6. The model is validated.
D.R. CHANDRAVANSHI
29. Continue………
7. If the model does not represent the data in a satisfactory manner,
then another model equation or new experimental design is selected.
Stages 3, 4, 5, and 6 are repeated using models and designs of
increasing complexity until a model is obtained, which is an acceptable
representation of the data.
8. If required, a graphical representation of the surface is generated.
D.R. CHANDRAVANSHI
30. RESPONSE SURFACES GENERATED FROM
FIRST-ORDER MODELS
The principles of response-surface methodology will first be described by a
very simple example that is then developed into a more complex situation.
The objective of the experiment is to investigate the response surface that
illustrates the influence of two factors, namely, compression pressure
(X1) and disintegrant concentration (X2), on the crushing strength of a
tablet formulation (Y1).
It is proposed to use a first-order model equation
Y1=β0+β1X1+β2X2+ε
The initial design is a two-factor, two-level study without replication. There
are thus four experiments in the design.
D.R. CHANDRAVANSHI
31. Continue……
The chosen values of the factors are 100 MPa and
300 MPa for compression pressure and 2.5% and 7.5% for disintegrant
concentration.
The lower value of each factor is designated −1 and the higher value +1.
The experimental design is shown in figure, and possible constraints
must now be considered.
With a linear relationship, there is no maximum or minimum value, and
hence in an unconstrained situation, there is an infinite number of
combinations of the two independent variables which will give a
specified value of the response. However, constraints are applicable to
this experiment.
D.R. CHANDRAVANSHI
32. Continue………
1. The compression pressure X1 cannot be less than 0 MPa. In terms of
experimental units (e.u.), X1 cannot be less than −2.
2. Likewise, the disintegrant concentration X2 cannot be less than 0% or −2
e.u.These two constraints represent the axes of Figure.
3. X1 cannot exceed the maximum pressure that the tablet press can safely
apply. This might be 400 MPa or +2 e.u.
4. The concentration of disintegrating agent (X2) cannot exceed a given
concentration limited by the formulation. This might be 10% or +2 e.u.
5.These constraints are represented by the axes of Figure . and the two
dotted lines drawn at +2 e.u. on each axis. However, it must be
remembered that the experimental data will be generated from a much
smaller domain, represented by the rectangle ABCD in Figure.
D.R. CHANDRAVANSHI
33. Continue……..
Figure:Two-factor, two-level factorial design to investigate the effect of
compression pressure and disintegrant concentration on tablet crushing
strength, showing constraints on the experimental domain.
D.R. CHANDRAVANSHI
34. The Effect of Compression Pressure and Disintegrant
Concentration on Tablet Crushing Strength, Using a
Two-Factor, Two-Level Design
Experiments Compression
pressure( Mpa)
(X1)
Disintegrant
concentration(%)
(X2)
Crushing strength
(kg)(Y1)
(-1,-1) 100 2.5 6.1
(+1,-1) 300 2.5 9.4
(-1,+1) 100 7.5 4.9
(+1,+1) 300 7.5 8.2
Tablets are prepared and the measured values of their crushing strengths
are shown in Table
The relative importance of the factors and the interaction on the tablet
crushing strength are now calculated .Thus, the effect of Factor X1,the
compression pressure on crushing strength (Y1),
Note: 1 e.u. of compression pressure = 100 MPa. 1 e.u. of disintegrant
concentration = 2.5%.
D.R. CHANDRAVANSHI
35. Continue….
Similarly, the effect of Factor X2, the disintegrant concentration, on crushing
strength (Y1)
Thus, both factors have a major influence. As might be expected, an increase
in the compression pressure has a positive effect on crushing strength and an
increase in the concentration of disintegrant has a negative effect. The next
stage is to fit the data from table into a regression equation of the form . This
gives Y1= 7.15 + 1.65X1− 0.6X2
D.R. CHANDRAVANSHI
36. The effect of compression pressure and disintegrant connc. On
tablet crushing strength, using a two factor, two level with
duplicated experiments at the center point.
Y1=β0+β1X1+β2X2+β12X1X2
Experi-
-ment
Compressio
n pressure
(Mpa)(X1)
Disintegra
nt conc.
(%)(X2)
Observed
crushing
strength(kg)Y
1
Crushing
strength
predicted
from(7.4)(kg
)
Residual
observed
value-
practical
value)(kg)
(-1,-1) 100 2.5 6.1 6.12 -0.02
(+1,-1) 300 2.5 9.42 9.42 -0.02
(-1,+1) 100 7.5 4.92 4.92 -0.02
(-1,-1) 300 7.5 8.2 8.22 -0.02
(0,0) 200 5.0 7.3 7.17 +0.13
(0,0) 200 5.0 7.1 7.17 -0.07
Note:-center point(0,0);compression pressure=200MPa;disintegrant
conc=5%,1e.u. of compression pressure=100MPa,1e.u. of disintegrant
conc.=2.5%.
D.R. CHANDRAVANSHI
37. Continue……..
Figuure:-The response surface of tablet crushing strength (kg) as
a function of compression pressure and disintegrant concentration,
using responses derived from previous table
D.R. CHANDRAVANSHI
38. It is now possible to answer a question such as “if tablets of a given
crushing strength (Y1) and containing a given concentration of
disintegrating agent (X2) are required, what compression pressure (X1)
is needed to produce them?” or, in general terms, “what values of the
factors are needed to give a product having specified properties?”
Equation can be rearranged to give
D.R. CHANDRAVANSHI
39. Y1 and X2 are specified, the coefficients are known, and the only
unknown is X1. For example, if the tablets are to contain 5%
disintegrating agent (zero when expressed in experimental units), and
should have a crushing strength of 6 kg, then eq…1 becomes eq….2
The required compression pressure is therefore −0.71 e.u., equivalent to
129 MPa.
X1=6-7.17-0.6×0/1.65
= -1.17/1.65
= 0.71
D.R. CHANDRAVANSHI
41. APPLICATION OF DESIGN OF EXPERIMENTS
Formulation and Processing.
Clinical Chemistry.
Medicinal Chemistry.
High Performance Liquid Chromatographic Analysis.
Study of Pharmacokinetic Parameters.
Allow large number of variables to be investigated in compact trial.
D.R. CHANDRAVANSHI
42. References
1.Roop Khar K,Vyas SP,Farhan Ahmad J,Gaurav jain K,”Industrial
Pharmacy”,CBS Publishers & Distributors New Delhi,Fourth
Edition,2013,356-361.
2.Tattawasart, A. and Armstrong, N. A., The formation of lactose plugs
for hard shell capsule fills, Pharm. Dev. Technol., 2, 335, 1997.
3. Pourkavoos, N. and Peck, G. E., Effect of aqueous film coating
conditions on water removal efficiency and physical properties of
coated tablet cores containing superdisintegrants,Drug Dev. Ind. Pharm.,
20, 1535, 1994.
D.R. CHANDRAVANSHI