A QUALITY BY DESIGN CONCEPT ON LIPID BASED NANOFORMULATION CONTAINING ANTIPSYCHOTIC DRUG: SCREEING DESIGN AND OPTIMIZATION USING RESPONSE SURFACE METHODOLOGY

1. Biplajit Das
M.Pharm(1st Semester)
Roll No-1991401019
School of Pharmaceutical Sciences
Shoolini University of Biotechnology and
Management Sciences, Himachal Pradesh,173229
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2. CONTENTS
 Introduction
 Materials & Methods
 Experimental Design
 Optimization Using Response Surface Methodology
 Characterization Of SLN
 Results And Discussion
 References
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3. INTRODUCTION
 SLN are colloidal systems composed of physiological and
biocompatible lipids that are solid at room temperature and
stabilize with non-toxic emulsifiers.
 It is biocompatible, improve drug dissolution and maintain
the controlled drug release.
 Asenapine maleate is an atypical antipsychotic drug , less
water soluble and for its extensive first past metabolism its
oral bioavailability is very less that’s why we proposed to
formulate SLN.
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4. Contd….
 Pharmaceutical formulation development involves complex
procedure which includes: ICH Q8 R2 & ICH Q9.
 Formulation Variable(Input Variable).
 Criticle Quality Attributes(CQA).
 Quality BY Design(QBD).
 Failure Mode Effects Analysis(FMEA).
 Failure Mode Effects and Criticality Analysis(FMECA).
 Cricticle Process Prameters(CPPs).
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5. MATERIALS AND METHODS
 Asenapine maleate, Glyceryl monostearate
 High Speed Homogenization:
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Melting the lipids(5°C) Add Drug
Dispersed it in aqueous surfactant Solution(At Same temperature using
homogenizer)
Emulsion is Ultrasonicated
Cooled
SLN

6. Experimental Design
 Initial risk assesment: Ishikawa diagram: To identify criticle
processing or formulation variables which can show it’s impact on
CQAs(PS & EE) of Asenapine meleate SLN.
 Preliminary investigation of critical variables: By changing
one variables at a time while keeping the other constant and the
effect of selected variables on Particle Size and Entrapment
Efficiency were studied to determine the optimal lower and upper
values for a screening design study.
 Risk analysis: Plackett Burman Design: Initial screening of
significant variables are carried out.
 Key factors: Homogenization speed(X₁), Homogenization
time(X₂), Sonication time(X₃),Sonication amplitude(X₄),
Concentration of surfactant(X₅), Concentration of lipid(X₆),
Concentration of drug(X₇). 6

7. OPTIMIZATION USING RESPONSE
SURFACE METHODOLOGY
 Central Composite Design: Used to statistically optimize
critical factor and to estimate main interaction, and
quadratic effect on product CQAs.
 Critical Factors(PBD): X₁, X₂, X₃.(Input Variables).
 Response surface plot useful to understand the effect of
two variables while third variable is constant.
 Establishment Of Design Space: JMP software
 Analysis Of Design Space robustness: Minitab 16
 Statistical Analysis:
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8. Characterization of SLN
 Determination of Particle Size: By photon correlation
spectroscopy using a Zetasizer Nano instruments.
 Determination of Entrapment Efficiency: By measuring the
amount of unentrapped drug in SLN dispersion.
%EE=
𝑇𝑜𝑡𝑎𝑙 𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑎𝑑𝑑𝑒𝑑−𝐹𝑟𝑒𝑒 𝑑𝑟𝑢𝑔
𝑇𝑜𝑡𝑎𝑙 𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑎𝑑𝑑𝑒𝑑
𝑥100
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9. Results and Discussion
 Screening of Solid Lipid: Use Glyceryl monostearate as a lipid
phase.
 Risk identification: Ishikawa diagram: Factor affecting CQAs of
SLN and these factors divided in three categories: Process,
formulation & environment.
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10. Contd….
 Preliminary investigation of critical variables:
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11. Analysis of critical variables using screening design:
PBD Influence on particle size and entrapment efficiency: PBD:
Pareto Charts:
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12. Optimization using CCD
 Influence of independent variables on particle size
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13. Contd….
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14. Contd….
 Influence Of Independent Variables On Entrapment Efficiency:
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15. Contd….
 Establishment Of Design Space:
 Design space is the space within which the quality of the product can be built
 The constraints for the responses were selected and predicted value was
compared with experimental value.
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16. Analysis of Design Space Robustness
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17. Conclusion
 A QbD concepts was used to understand the effect of various
formulation and process variable on CQAs of SLN such as
particle size and entrapment efficiency. Ishikawa diagram aided
in the initial risk assesment for formulation development
process. Preliminary investigation helped to define the range
for each factor for further study. PPD & CCD were useful to
fully understand the influence of various variables of high
speed homogenization followed by ultrasonication method and
their relative influence in product quality attributes. Statistical
investigation of AS SLN formulation confirmed the potential of
QbD concept in optimization of indipendent variables for SLN
preparation.
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18. REFERENCES
 Cai S, Zhang Q, Bagby T, Forrest M (2011), “Lymphatic
drug delivery using engineered liposomes and solid lipid
nanoparticles”, Advance drug delivery review, 19(2):901-
908.
 Paliwal R, Rai S, Vaidya B, Khatri K, Goyal A(2009),
“Effect of lipid core material on characteristics of solid
lipid nano particles for lymphatic delivery”,
Nanomedicine: Nanotechnology, Biology and Medicine,
(16)1:184-191.
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