WEIGHT VARIATION

FOR SOFT GELATIN CAPSULE DEVELOPMENT AS PER QbD

OPTIMIZATION OF CPPs OF SOFT GELATIN CAPSULE ENCAPSULATION PROCESS

IN-PROCESS IMPURITIES

QUALITY COMPROMISED PATIENT SAFETY COMPROMISED

IMPROPER MACHINE SPEED HIGHER TEMPERATURE

FACTORIAL MIXTURE

BOX BEHNKEN

RESPONSE SURFACE

CIRCUMSCRIBED CENTRAL COMPOSITE

MELTING/ HEATING TEMPERATURE

GELATIN LAYER THICKNESS

ROTARY DIE SPEED

3

2

1

DEVELOPMENT OF DESIGN SPACE

ANALYSIS OF RESPONSES

DESIGN OF EXPERIMMENTS

IDENTIFICATION OF FACTORS

CA

SE

STU

DY

12

RISKS

INADEQUATE DRUG RELEASE

EFFICACY COMPROMISED

THICKENED SOFTGEL LAYER

© 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

DEVELOPMENT OF DESIGN SPACE

Factors (Variables) Levels of Factors studied -α -1 0 +1 +α

A Melting/ Heating Temperature (°C) 52.9 55.0 60.0 65.0 67.1 B Gelatin Layer Thickness (mm) 0.46 0.50 0.60 0.70 0.74 C Rotary Die Speed (RPM) 1.59 2.00 3.00 4.00 4.41

NO. OF FACTORS

NO. OF LEVELS

EXPERIMENTAL DESIGN SELECTED

ADD. CENTER POINTS

TOTAL NO OF EXPERIMENTAL RUNS (NO OF TRIALS)

3

5

CIRCUMSCRIBED CENTRAL COMPOSITE RSM WITH FRACTIONAL FACTORIAL (SCALE DOWN CCD)

4

4 ffp + 6sp + 5cp =15

OBJECTIVE To Optimize CPPs of Encapsulation Process for Soft Gelatin Capsule

© Created & Copyrighted by Shivang Chaudhary

FACTORIAL MIXTURE

BOX BEHNKEN

RESPONSE SURFACE

ANALYSIS OF RESPONSES

IDENTIFICATION OF FACTORS

DESIGN OF EXPERIMMENTS

OPTIMIZATION OF CPPs OF SOFTGEL CAPSULE ENCAPSULATION PROCESS

A MELTING TEMPERATURE

C

RO

TAR

Y D

IE S

PE

ED

CIRCUMSCRIBED CENTRAL COMPOSITE C

ASE

ST

UD

Y 1

2

© Created & Copyrighted by Shivang Chaudhary

IDENTIFICATION OF FACTORS

DEVELOPMENT OF DESIGN SPACE

CQAs CPP

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

DISSOLUTION AT 30 MINS=+96.56-2.12A-7.78B+2.12C+1.87AB-2.03AC+0.63BC-3.97A2-5.97B2-3.47C2

%TOTAL IMPURITIES =+1.40+0.81A-0.035B-0.28C-0.033AB+0.015AC+0.063BC+0.54A2+0.044B2+0.22C2

WEIGHT VARIATION =+1.28-0.21A+0.035B+0.60C+0.13AB+0.010AC-0.44BC+0.28A2+0.31B2+1.01C2

© Created & Copyrighted by Shivang Chaudhary

FACTORIAL MIXTURE

BOX BEHNKEN

RESPONSE SURFACE

DESIGN OF EXPERIMMENTS

ANALYSIS OF RESPONSES

OPTIMIZATION OF CPPs OF SOFTGEL CAPSULE ENCAPSULATION PROCESS

CIRCUMSCRIBED CENTRAL COMPOSITE C

ASE

ST

UD

Y 1

2

© Created & Copyrighted by Shivang Chaudhary

IDENTIFICATION OF FACTORS

DESIGN OF EXPERIMMENTS

Responses (Effects) Goal for Individual Responses Y1 Weight variation (%) Weight variation should not be more than i.e. NMT 1.5%RSD Y2 Drug Dissolved at 30 min %Drug dissolved should not be less than 90% Y3 Total Impurities (%) Total Impurities should not be increased more than 1.5%w/w

Factors (Variables) Knowledge Space Design Space Control Space A Melting/ Heating Temperature (°C) 53-67 57-60 58-60 B Gelatin Layer Thickness (mm) 0.46-0.74 0.52-0.62 0.54-0.60 C Rotary Die Speed (RPM) 1.6-4.4 2.25-3.25 2.50-3.00

FACTORIAL MIXTURE

BOX BEHNKEN

RESPONSE SURFACE

ANALYSIS OF RESPONSES

DEVELOPMENT OF DESIGN SPACE

OPTIMIZATION OF CPPs OF SOFTGEL CAPSULE ENCAPSULATION PROCESS

CIRCUMSCRIBED CENTRAL COMPOSITE C

ASE

ST

UD

Y 1

2

© 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

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

facebook.com/QbD.PAT.Pharmaceutical.Development