FOR HARD GELATIN CAPSULE DEVELOPMENT AS PER QbD
OPTIMIZATION OF CMAs & CPPs OF HARD GELATIN ENCAPSULATION PROCESS
INADEQUATE DISINTEGRATION
QUALITY COMPROMISED EFFICACY COMPROMISED SAFETY COMPROMISED
RISKS
WEIGHT VARIATION & CONTENT NON UNIFORMITY
INAPPROPRIATE FLOW PROPERTY & FILLING RATE
INADEQUATE DISSOLUTION
FACTORIAL MIXTURE
CENTRAL COMPOSITE
RESPONSE SURFACE
BOX BEHNKEN
DEVELOPMENT OF DESIGN SPACE
ANALYSIS OF RESPONSES
DESIGN OF EXPERIMMENTS
IDENTIFICATION OF FACTORS
A GLIDANT
B ANTIADHERANT
C FILLING RATE
CA
SE
STU
DY
17
© 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
Factors (Variables) Levels of Factors Studied -1 0 +1
A Glidant (%w/w) 0.10%w/w 0.25%w/w 0.40%w/w B Lubricant (%w/w) 0.50%w/w 1.25%w/w 2.00%w/w C Filling Rate (SPM) 50SPM 65SPM 80SPM
NO. OF FACTORS
NO. OF LEVELS
EXPERIMENTAL DESIGN SELECTED
ADD. CENTER POINTS
TOTAL NO OF EXPERIMENTAL RUNS (NO OF TRIALS)
3
3
BOX BEHNKEN DESIGN
2
12 + 3CP =15
To Optimize CMAs & CPPs of Hard Gelatin Capsule Encapsulation. OBJECTIVE
DEVELOPMENT OF DESIGN SPACE
ANALYSIS OF RESPONSES
FACTORIAL MIXTURE
CENTRAL COMPOSITE
RESPONSE SURFACE
BOX BEHNKEN
IDENTIFICATION OF FACTORS
DESIGNING OF EXPERIMMENTS
OPTIMIZATION OF CMAs & CPPs OF HARD GELATIN CAPSULE ENCAPSULATION
A GLIDANT
C
FIL
LIN
G R
ATE
CA
SE
STU
DY
17
© Created & Copyrighted by Shivang Chaudhary
IDENTIFICATION OF FACTORS
PREDICTION EFFECT EQUATION OF EACH FACTOR, THEIR INTERACTIONS & CURVATURES ON INDIVIDUAL RESPONSE BY QUADRATIC MODEL
Weight Variation =+1.53-0.34A-0.10B+0.49C-0.00AC-0.075AC-0.00BC+0.37A2+0.30B2+0.92C2
Content Uniformity=+1.80-0.44A-0.14B+0.58C+0.075AB-0.050AC+0.100BC+0.44A2+0.29B2+1.11C2
Plug Breaking Force =+1.53+0.025A-0.26B-0.76C-0.13AB-0.075AC-0.050BC+0.058A2 -0.017B2+0.18C2
Disintegration Time =+3.17+0.000A-0.50B-1.78C-0.22AB+0.025AC-0.075BC+0.054A2+0.054B2+0.40C2
CMAs CPP
%Drug Dissolved in 30 minutes =+95.67+0.37A-2.13B+7.75C+0.000AB-1.25AC-3.75BC-3.08A2-5.58B2-4.83C2
CQAs
DEVELOPMENT OF DESIGN SPACE
FACTORIAL MIXTURE
CENTRAL COMPOSITE
RESPONSE SURFACE
DESIGN OF EXPERIMMENTS
BOX BEHNKEN
ANALYSIS OF RESPONSES
OPTIMIZATION OF CMAs & CPPs OF HARD GELATIN CAPSULE ENCAPSULATION
CA
SE
STU
DY
17
© Created & Copyrighted by Shivang Chaudhary
IDENTIFICATION OF FACTORS
DESIGN OF EXPERIMMENTS
Factors (Variables) Knowledge Space Design Space Control Space A Glidant (%) 0.10-0.50 0.20-0.40 0.20-0.40 B Lubricant (%) 0.50-2.00 0.70-1.80 0.90-1.60 C Filling Rate (SPM) 50-80 56-68 58-66
Responses (Effects) Goal for Individual Responses Y1 Weight Variation Relative Standard Deviation in WV test should NMT 2.0% Y2 Content Uniformity Acceptance Value in CU test should NMT 4.0 Y3 Hardness Force required to break the plug should NMT 2N Y4 Disintegration To achieve complete disintegration (no residue) within 5 minutes Y5 Dissolution To achieve at least 90% drug release within 30 minutes
ANALYSIS OF RESPONSES
FACTORIAL MIXTURE
CENTRAL COMPOSITE
RESPONSE SURFACE
BOX BEHNKEN
DEVELOPMENT OF DESIGN SPACE
OPTIMIZATION OF CMAs & CPPs OF HARD GELATIN CAPSULE ENCAPSULATION
CA
SE
STU
DY
17
© 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]
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