optimization of cpps of sublimation phase (1° drying) of “lyophilization process” using face...
TRANSCRIPT
FOR DEVELOPMENT OF FREEZE DRIED RECONSTITUTED DOSAGE FORM AS PER QbD
OPTIMIZATION OF CPPs OF SUBLIMATION PHASE (1° DRYING) OF LYOPHILILIZATION PROCESS
RISKS
PRODUCT TEMPERATURE DURING PRIMARY DRYING TOTAL DURATION OF PRIMARY DRYING
QUALITY COMPROMISED
EXCEEDS CRITICAL TEMPERATURE (Tcol FOR AMORPHOUS/ Teut FOR CRYSTALLINE)
EXCEEDS MAXIMUM TIME TO ACCOMMODATE THE PLANT’S DEMANDS FOR PRODUCT SUPPLY
PATIENT ACCEPTANCE COMPROMISED
CAKE APPEARANE COMPROMISED (COLLAPSE/MELT) MFG COST OF THE D PRODUCT INCREASED
FACTORIAL MIXTURE
BOX BEHNKEN
RESPONSE SURFACE
FACE CENTERED CENTRAL COMPOSITE
CHAMBER PRESSURE
SHELF TEMPERATURE A
B
DEVELOPMENT OF DESIGN SPACE
IDENTIFICATION OF FACTORS
ANALYSIS OF RESPONSES
DESIGNING OF EXPERIMMENTS
CA
SE
STU
DY
14
© 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
DEVELOPMENT OF DESIGN SPACE
IDENTIFICATION OF FACTORS
Factors (Variables) Levels of Factors studied -1 0 +1
A Shelf Temperature ( ͦC) -10C +5C +20 ͦC B Chamber Pressure (Pa) 10 Pa (o.1mbar) 15 Pa 20 Pa (0.2mbar)
NO. OF FACTORS
NO. OF LEVELS
EXPERIMENTAL DESIGN SELECTED
ADD. CENTER POINTS
TOTAL NO OF EXPERIMENTAL RUNS (NO OF TRIALS)
2
3
FACE CENTERED CENTRAL COMPOSITE RSM for 2 factors
4
4FP +4SP+5CP =13
To Optimize CPPs of Sublimation Phase (Primary Drying Step) of Freeze Drying Process for Reconstituted Powders
OBJECTIVE
FACTORIAL MIXTURE
BOX BEHNKEN
RESPONSE SURFACE
ANALYSIS OF RESPONSES
DESIGNING OF EXPERIMMENTS
OPTIMIZATION OF CPPs OF FREEZE DRYING PROCESS FOR RECONSTITUTED POWDERS
A SHELF TEMPERATURE
B
CH
AM
BE
R P
RE
SSU
RE
FACE CENTERED CENTRAL COMPOSITE C
ASE
ST
UD
Y 1
4
© Created & Copyrighted by Shivang Chaudhary
DEVELOPMENT OF DESIGN SPACE
IDENTIFICATION OF FACTORS
PREDICTION EFFECT EQUATION OF EACH FACTOR, THEIR INTERACTIONS & CURVATURES ON INDIVIDUAL RESPONSE BY QUADRATIC MODEL
Product Temperature=-16.21+7.00A+1.50B+0.000AB-0.28A2+0.22B2
Total Drying Time =+39.86-27.33A-7.83B+4.00AB+0.48A2+1.98B2
CQAs CPPs
FACTORIAL MIXTURE
BOX BEHNKEN
RESPONSE SURFACE
design of experimments
ANALYSIS OF RESPONSES
OPTIMIZATION OF CPPs OF FREEZE DRYING PROCESS FOR RECONSTITUTED POWDERS
FACE CENTERED CENTRAL COMPOSITE C
ASE
ST
UD
Y 1
4
© Created & Copyrighted by Shivang Chaudhary
IDENTIFICATION OF FACTORS
design of experimments
Factors (Variables) Knowledge Space Design Space Control Space A Shelf Temperature ( ͦC) -10°C - +20°C -2.5 - +17.5°C 0°C- +15°C B Chamber Pressure (Pa) 10-20 10-20 10-20Pa (0.1-0.2mbar)
Responses (Effects) Goals for Individual Responses Y1 Product
Temperature should be maintained below critical product temperature i.e. -12°C to prevent collapse of the structure to get the desired cake appearance
Y2 Primary Drying Time
should be less than 48 hours (2day) to control processing cost &
ultimately to control product price for high patient acceptance
FACTORIAL MIXTURE
BOX BEHNKEN
RESPONSE SURFACE
ANALYSIS OF RESPONSES
DEVELOPMENT OF DESIGN SPACE
OPTIMIZATION OF CPPs OF FREEZE DRYING PROCESS FOR RECONSTITUTED POWDERS
FACE CENTERED CENTRAL COMPOSITE C
ASE
ST
UD
Y 1
4
© 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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