TESTING OF SIGNIFICANCE

NO. OF FACTORS

NO. OF LEVELS

EXPERIMENTAL DESIGN SELECTED

TOTAL NO OF EXPERIMENTAL RUNS (NO OF TRIALS)

4

2

FRACTIONAL FACTORIAL DESIGN

24-1

= 8

BINDER SOLUTION ADDITION TIME

KNEADING (MIXING & GRANULATION) TIME

CHOPPER (GRANULATOR) SPEED

IMPELLER (MIXER) SPEED A

B

C

D

SCREENING OF CPPs OF HIGH SHEAR WET GRANULATION PROCESS

© Created & Copyrighted by Shivang Chaudhary

FOR SOLID ORAL DOSAGE FORMS DEVELOPMENT AS PER QbD

3 LEVEL FACTORIAL

PLACKETTE BURMAN

SCANNING OF EFFECTS

ANALYSIS OF RESPONSE

DESIGNING OF EXPERIMMENTS

IDENTIFICATION OF FACTORS

MIXTURE RESPONSE SURFACE FACTORIAL

2 LEVEL FRACTIONAL FACTORIAL C

ASE

ST

UD

Y 2

© Created & Copyrighted by Shivang Chaudhary

SHIVANG CHAUDHARY Created & Copyrighted by:

Quality Risk Manager & Intellectual Property Sentinel- CIIE, IIM Ahmedabad, INDIA MS Pharm (Pharmaceutics)-NIPER, PGD (Patents Law)-NALSAR

shivaniper@gmail.com

TESTING OF SIGNIFICANCE

SCANNING OF EFFECTS

SCREENING OF CPPs OF HIGH SHEAR WET GRANULATION PROCESS FOR SOLID ORAL DOSAGE FORM

Factors (Variables) Levels of Factors studied -1 +1

A BINDER ADDITION TIME (min) 1 2 B IMPELLER-MIXER SPEED (RPM) 50 100 C CHOPPER-GRANULATOR SPEED (RPM) 1000 3000 D KNEADING TIME (min) 3 5

Responses (Effects) Goals for Individual Responses Y1 %FINES To achieve minimum fines after granulation i.e. NMT 10%

Y2 % AGGLOMERATES To achieve minimum agglomerates after granulation i.e. NMT 10%

FACTORS TO BE STUDIED

RESPONSES TO BE MEASURED

OBJECTIVE To Screen Out Critical Processing Parameters of High Shear Wet Granulation Process.

3 LEVEL FACTORIAL

PLACKETTE BURMAN

IDENTIFICATION OF FACTORS

ANALYSIS OF RESPONSE

DESIGNING OF EXPERIMMENTS

MIXTURE RESPONSE SURFACE FACTORIAL

2 LEVEL FRACTIONAL FACTORIAL C

ASE

ST

UD

Y 2

© Created & Copyrighted by Shivang Chaudhary

TESTING OF SIGNIFICANCE

CQAs CPPs

3 LEVEL FACTORIAL

PLACKETTE BURMAN

IDENTIFICATION OF FACTORS

DESIGNING OF EXPERIMMENTS

SCANNING OF EFFECTS

ANALYSIS OF RESPONSE

SCREENING OF CPPs OF HIGH SHEAR WET GRANULATION PROCESS FOR SOLID ORAL DOSAGE FORM

MIXTURE RESPONSE SURFACE FACTORIAL

2 LEVEL FRACTIONAL FACTORIAL C

ASE

ST

UD

Y 2

© Created & Copyrighted by Shivang Chaudhary

TESTING OF SIGNIFICANCE

SIGNIFICANT EFFECTS: MODEL TERMS

SIGNIFICANT EFFECTS: MODEL TERMS

NEGLIGIBLE TERMS: ERROR ESTIMATES

NEGLIGIBLE TERMS: ERROR ESTIMATES

Thus, IMPPELER & CHOPPER SPEED & KNEADING time are the most critical factors those required to control the ultimate particle size during fluid bed granulation

© Created & Copyrighted by Shivang Chaudhary

3 LEVEL FACTORIAL

PLACKETTE BURMAN

IDENTIFICATION OF FACTORS

DESIGNING OF EXPERIMMENTS

ANALYSIS OF RESPONSE

SCANNING OF EFFECTS

%Fines = +10.63 -2.13B +1.38C -4.38D %Agglomerates = +9.63 +2.62B -1.38C +4.88D

SCREENING OF CPPs OF HIGH SHEAR WET GRANULATION PROCESS FOR SOLID ORAL DOSAGE FORM

MIXTURE RESPONSE SURFACE FACTORIAL

2 LEVEL FRACTIONAL FACTORIAL C

ASE

ST

UD

Y 2

© Created & Copyrighted by Shivang Chaudhary

Ho There Is No Significant Effect Of Selected Processing Parameters (PP) On Response (CQA)

ANOVA Response 1: FINES ANOVA Response 2: AGGLOMERATES

3 LEVEL FACTORIAL

PLACKETTE BURMAN

IDENTIFICATION OF FACTORS

DESIGNING OF EXPERIMMENTS

ANALYSIS OF RESPONSE

SCANNING OF EFFECTS

TESTING OF SIGNIFICANCE

SCREENING OF CPPs OF HIGH SHEAR WET GRANULATION PROCESS FOR SOLID ORAL DOSAGE FORM

MIXTURE RESPONSE SURFACE FACTORIAL

2 LEVEL FRACTIONAL FACTORIAL C

ASE

ST

UD

Y 2

F Value = Test For Comparing MODEL VARIANCE

(SIGNAL=Predicted value) with RESIDUAL VARIANCE

(NOISE=(Observed-Predicted value))

p-value = Probability of Falsely Detecting the Significant Effect

(also called as a Level of Significance (α))

Reject Ho&

Accept Ha Conclude that there is a

significant effect of A & B Processing

Parameters on CQA p Value =α < 0.05 for CI= 95%

F Value= (MS Model/ MS Residuals) >1

Conclude that there is only a 0.01% chance that

A "Model F-Value" this large could

occur due to noise.

Significant Signal Negligible Noise

From the results of designed experiments on limited samples, Experimenter has 95% confidence that 99% population will meet the same specification within predefined targets

© Created & Copyrighted by Shivang Chaudhary

THANK YOU SO MUCH FROM

DESIGN IS A JOURNEY OF DISCOVERY…

© Created & Copyrighted by Shivang Chaudhary

SHIVANG CHAUDHARY

© Copyrighted by Shivang Chaudhary

Quality Risk Manager & Intellectual Property Sentinel- CIIE, IIM Ahmedabad MS (Pharmaceutics)- National Institute of Pharmaceutical Education & Research (NIPER), INDIA

PGD (Patents Law)- National academy of Legal Studies & Research (NALSAR), INDIA

+91 -9904474045, +91-7567297579 shivaniper@gmail.com

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