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    Factorial Design

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    sarmiladz2077
    - The document discusses various optimization techniques used in pharmaceuticals including factorial design, fractional factorial design, Box-Behnken design, and general optimization methods. - Factorial designs are used to determine the effects of several factors and their interactions, and can be full or fractional. Fractional factorial designs more efficiently examine multiple factors with fewer experiments. - Other techniques discussed include Box-Hunter designs, Plackett-Burman screening designs, Taguchi designs, and Latin square designs. Evolutionary operations, simplex method, Lagrangian method, search method, and canonical analysis are also optimization methods covered.

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    Factorial Design

    Uploaded by

    sarmiladz2077
    111 views30 pages
    - The document discusses various optimization techniques used in pharmaceuticals including factorial design, fractional factorial design, Box-Behnken design, and general optimization methods. - Factorial designs are used to determine the effects of several factors and their interactions, and can be full or fractional. Fractional factorial designs more efficiently examine multiple factors with fewer experiments. - Other techniques discussed include Box-Hunter designs, Plackett-Burman screening designs, Taguchi designs, and Latin square designs. Evolutionary operations, simplex method, Lagrangian method, search method, and canonical analysis are also optimization methods covered.

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    - The document discusses various optimization techniques used in pharmaceuticals including factorial design, fractional factorial design, Box-Behnken design, and general optimization methods. - Factorial designs are used to determine the effects of several factors and their interactions, and can be full or fractional. Fractional factorial designs more efficiently examine multiple factors with fewer experiments. - Other techniques discussed include Box-Hunter designs, Plackett-Burman screening designs, Taguchi designs, and Latin square designs. Evolutionary operations, simplex method, Lagrangian method, search method, and canonical analysis are also optimization methods covered.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    111 views30 pages

    Factorial Design

    Uploaded by

    sarmiladz2077
    - The document discusses various optimization techniques used in pharmaceuticals including factorial design, fractional factorial design, Box-Behnken design, and general optimization methods. - Factorial designs are used to determine the effects of several factors and their interactions, and can be full or fractional. Fractional factorial designs more efficiently examine multiple factors with fewer experiments. - Other techniques discussed include Box-Hunter designs, Plackett-Burman screening designs, Taguchi designs, and Latin square designs. Evolutionary operations, simplex method, Lagrangian method, search method, and canonical analysis are also optimization methods covered.

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    OPTIMIZING

    TECHNIQUES IN
    PHARMACEUTICALS
    OPTIMIZING TECHNIQUES IN PHARMACEUTICALS
    FACTORIAL DESIGN
    Full used for small set of factors
    Fractional used to examine multiple factors efficiently with fewer runs
    than corresponding full factorial design
    Types of fractional factorial designs
    • Homogenous fractional
    • Mixed level fractional
    • Box-Hunter
    • Plackett-Burman
    • Taguchi
    • Latin square
    Factorial Design
    1.Homogenous fractional:
    • useful when large number of factors must be screened.
    2 Mixed level fractional:
    • useful when variety of factors are needed to be evaluated for
    main effects and higher level interactions can be assumed to
    be negligible.
    3.Box-Hunter:
    • fractional designs with factors of more than 2 levels can be
    specified as homogenous fractional or mixed level fractional.
    4. Plackett-Burman:

    • it is a popular class of screening design.


    • these designs are very efficient screening designs when only main
    effects are of interest.
    • useful for detecting large main effects economically, assuming all
    interactions are negligible when compared with important effects.
    • used to investigate n-1 variables in n experiments proposing
    experimental designs for more than seven factors.
    5. Taguchi:
    It allows estimation of main effects while minimizing variance
    6. Latin square:
    These are special case of fractional factorial design where there
    is one treatment factor of interest and two or more blocking
    factors.
    BOX-BEHNKEN DESIGN

    • They do not contain embedded factorial or fractional factorial design.


    • Box-Behnken designs use just three levels of each factor.
    • These designs for three factors with circled point appearing at the
    origin and possibly repeated for several runs
    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 & high values.
    • These values are usually expressed as 0,1 and 2
    • The third level for a continuous factor facilitates investigation of a
    quadratic relationship between the response and each of the factors.
    FACTORIAL DESIGN

    • These are the designs of choice for simultaneous determination of the


    effects of several factors & their interactions.
    • They are used in experiments where the effects of different factors or
    conditions on experimental results are to be elucidated.
    Two types
    • Full factorial-Used for small set of factors
    • Fractional factorial-for optimizing more number of factors
    GENERAL OPTIMIZATION

    • By the relationships are generated from experimental data, resulting


    equations are on the basis of optimization.
    • These equation defines response surface for the system under
    investigation.
    • After collection of all the rans and calculated responses calculation of
    regression coefficient is initiated.
    • Analysis of variance (ANOVA) presents the sum of the squares used to
    estimate the factor main effects
    • Considering the changes in input and effect on output, the
    optimization techniques are categorized into 5 types:
    Applied optimization methods
    1. Evolutionary operations
    2. simplex method
    3. Lagrangian method
    4. search method
    5. canonical analysis.
    Evolutionary operations (EVOP)

    • It is a method of experimental optimization.

    • Technique is well suited for production (formulation process)

    • Small changes in formulation process are made(ie., repeated


    experimentation & statistically analysed for improvement.)

    • It continues until no further changes takes place ie., it has reached


    optimum the peak
    EVOLUTIONARY OPERATIONS (EVOP)

    • Applied mostly to TABLETS.

    • Production procedure is optimized by careful planning and constant


    repetition.

    • It is impractical and expensive to use.


    SIMPLEX METHOD

    • It is an experimental method applied for pharmaceutical systems.


    • Technique has wider appeal in analytical method other than
    formulation and processing
    • Simplex is a geometric figure that has one more point than the no. of
    factors.
    • It is represented by triangle.
    • It is determined by comparing the magnitude responses after each
    successive calculation.
    SIMPLEX METHOD

    • The two independent variables show pump speeds for the two
    reagents required in the analysis reaction.
    • Initial simplex is represented by lowest triangle
    • The vertices represents spectrophotometric response.
    • The strategy is to move towards a better response by moving away
    from worst response.
    • Applied to optimize CAPSULES, DIRECT COMPRESSION
    TABLET(acetaminophen), liquid systems (physical stability)
    LAGRANGIAN METHOD

    • It represents mathematical techniques.


    • It is an extension of classic method.
    • It is applied to a pharmaceutical formulation and processing.
    • This technique follows the second type of statistical design.
    • Limited to 2 variables -disadvantage
    STEPS INVOLVED(EXAMPLE)

     Optimization of a tablet
    • Phenyl propranolol (active ingredient)-kept constant
    • X1-disintegrate (corn starch)
    • X2-lubricant (stearic acid)
    • X1 & X2 are independent variables
    • Dependent variables include tablet hardness, friability, volume, in-
    vitro release rate etc.
    LAGRANGIAN METHOD

    • Constrained optimization problem is to locate the levels of stearic acid


    (x1) and starch (x2)
    • This minimize the time of in-vitro release Y2 average tablet volume Y4
    average Inability(Y3)
    • To apply the lagrangian method, problem must he expressed
    mathematically as follows
    • Y2=f1(X1X2) in vitro release
    • Y3=f3(X1X2)<2.72-Friability
    • Y4=f4(X1X2)<0.422-avgtab vol
    SEARCH METHOD

    • It is defined by appropriate equations.


    • It do not require continuity or differentiability of function.
    • It is applied to pharmaceutical system
    • For optimization 2 major steps are used
    • Feasibility search-used to locate set of response constraints that are
    just at the limit of possibility
    • Grid search - experimental range is divided in to grid of specific size &
    methodically searched.
    Steps involved in search method
    • Select a system
    • Select variables
    • Perform experiments and test product
    • Submit data for statistical and regression analysis
    • Set specifications for feasibility program
    • Select constraints for grid search
    • Evaluate grid search printout
    Examples of dependent and independent variables

    Independent variables Dependent variables


    X1 Diluent ratio Y1 disintegration time
    X2 compressional force Y2 hardness
    X3 disintegrant level Y3 dissolution
    X4 binder level Y4 friability
    X5 lubricant level Y5 weight uniformity
    CONONICAL ANALYSIS

    • It is a technique used to reduce a second order regression equation.

    • This allows immediate interpretation of the regression equation by


    including the linear and interaction terms in constant term.
    THANK YOU

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