Optimization of CMAs & CPPs of “High Shear Wet Granulation” Process using Face Centered Central Composite RSM for Development of Solid Oral Dosage Forms as per QbD

FOR SOLID ORAL DOSAGE FORMS DEVELOPMENT AS PER QbD

OPTIMIZATION OF CMAs & CPPs OF HIGH SHEAR WET GRANULATION PROCESS

RISKS

LOWER HARDNESS INADEQUATE DISINTEGRATION

QUALITY COMPROMISED EFFICACY COMPROMISED

HIGH FRIABILITY INADEQUATE DISSOLUTION

SOFT GRANULES HARD GRANULES

FACTORIAL MIXTURE

BOX BEHNKEN

RESPONSE SURFACE

FACE CENTERED CENTRAL COMPOSITE

BINDER

DISINTEGRANT

KNEADING TIME C

B

A

DEVELOPMENT OF DESIGN SPACE

ANALYSIS OF RESPONSES

DESIGN OF EXPERIMMENTS

IDENTIFICATION OF FACTORS

CA

SE

STU

DY

15

© 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

[email protected]

IDENTIFICATION OF FACTORS

DEVELOPMENT OF DESIGN SPACE

Factors (Variables) Levels of Factors Studied -α = -1 0 +α = +1

A Binder (%w/w) 4% 7% 10% B Disintegrant (%w/w) 1% 3% 5% C Kneading Time (min) 2 min 4 min 6 min

NO. OF FACTORS

NO. OF LEVELS

EXPERIMENTAL DESIGN SELECTED

ADD. CENTER POINTS

TOTAL NO OF EXPERIMENTAL RUNS (NO OF TRIALS)

3

3

FACE CENTERED CENTRAL COMPOSITE DESIGN

5

8fp + 6sp + 6cp =20

OBJECTIVE To Optimize CMAs & CPPs of Wet Granulation Process

FACTORIAL MIXTURE

BOX BEHNKEN

RESPONSE SURFACE

ANALYSIS OF RESPONSES

DESIGN OF EXPERIMMENTS

OPTIMIZATION OF CMAs & CPP OF HIGH SHEAR WET GRANULATION PROCESS FOR SOLID ORALS

A BINDER

C

KN

EA

DIN

G T

IME

FACE CENTERED CENTRAL COMPOSITE C

ASE

ST

UD

Y 1

5

© Created & Copyrighted by Shivang Chaudhary

IDENTIFICATION OF FACTORS

DEVELOPMENT OF DESIGN SPACE

DESIGNING OF EXPERIMMENTS

CQAs CMAs CPP

PREDICTION EFFECT EQUATION OF EACH FACTOR, THEIR INTERACTIONS & CURVATURES ON INDIVIDUAL RESPONSE BY QUADRATIC MODEL

HARDNESS =+74.80+11.80A-3.10B+15.10C-1.25AB+3.75AC+1.25BC+0.000A2-0.50B2-6.50C2

FRIABILITY=+0.11-0.050A+0.012B-0.069C+3.750E-003AB-0.016AC-8.750E-003BC+0.021A2+0.011B2+0.036C2

DISINTEGRATION TIME=+8.05+3.40A-2.30B+2.00C +0.50AB-0.25 AC+0.75BC+1.14A2+2.64B2+1.14C2

DRUG DISSOLVED=+93.44-9.20A+2.70B-4.80C+0.000AB+0.75AC-0.50BC-6.09A2-0.59B2-4.09 C2

FACTORIAL MIXTURE

BOX BEHNKEN

RESPONSE SURFACE

ANALYSIS OF RESPONSES

OPTIMIZATION OF CMAs & CPP OF HIGH SHEAR WET GRANULATION PROCESS FOR SOLID ORALS

FACE CENTERED CENTRAL COMPOSITE C

ASE

ST

UD

Y 1

5

© Created & Copyrighted by Shivang Chaudhary

IDENTIFICATION OF FACTORS

Responses (Effects) Goal for Individual Responses Y1 Hardness (n) To achieve tablet hardness in the range from 65 to 85N Y2 Friability (%) To achieve minimum friability i.e. NMT 0.15% Y3 Disintegration (min) To achieve tablet DT within 10 minutes Y4 Dissolution (%) To achieve maximum dissolution in 30 minutes i.e. NLT 90%

Factors (Variables) Knowledge Space Design Space Control Space A Binder (%) 4-10 5.3-8.8 6.0-8.0 B Disintegrant (%) 1-5 2.2-4.4 3.0-4.0 c Kneading Time (min) 2-6 2.0-5.0 2.5-4.5

FACTORIAL MIXTURE

BOX BEHNKEN

RESPONSE SURFACE

DESIGN OF EXPERIMMENTS

ANALYSIS OF RESPONSES

DEVELOPMENT OF DESIGN SPACE

OPTIMIZATION OF CMAs & CPP OF HIGH SHEAR WET GRANULATION PROCESS FOR SOLID ORALS

FACE CENTERED CENTRAL COMPOSITE C

ASE

ST

UD

Y 1

5

© 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 [email protected]

https://in.linkedin.com/in/shivangchaudhary

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