“Formulation & Characterization of the C-SLNs to enhance the Drug loading as well as Bioavailability of Curcumin”

1. “Formulation & Characterization of the C-SLNs to enhance
the Drug loading as well as Bioavailability of
Curcumin”
N.D.M.V.P. Samaj’s College of Pharmacy, Gangapur Road, Nashik 422 002
Presented by- Under the guidance of
NITIN KANWALE Dr. M.H. BELE
M. Pharm (QAT) Department of Pharmaceutics
1

2. OUTLINES
Introduction
Research Question
Literature review
Aim and objectives
Drug profile
Polymer profile
Plan of work
Experimental section
Results
References
2

3. INTRODUCTION
The solid lipid nanoparticles are submicron colloidal carriers (50-1000 nm) which are
composed of physiological lipid, dispersed in water or in an aqueous surfactant solution.
 SLNs were invented at the beginning of 1990s and are produced either by high-pressure
homogenization or by microemulsion technique and are considered to be the most effective lipid
based colloidal carriers.
 Aims of SLNs:- - Possibility of controlled drug release and drug targeting.
- Increased drug stability and high drug payload.
- Incorporation of lipophilic and hydrophilic drugs feasible.
- No biotoxicity of the carrier.
- Avoidance of organic solvents.
- No problems with respect to large scale production and sterilization.
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4. Cont…
Figure:1 Proposed structure of SLNs
Figure:2 Difference b/w Liposome and SLNs
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5. Cont…
 Materials used for the formulation of the SLNs:-
1.API
2.Lipid
3.Surfactant (Emulsifiers)
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6. High shear homogenization with Ultrasonication
• It involves high pressure homogenization which pushes the liquid with high
pressure (100-2000 bar) through a narrow gap ranging a few microns.
• The fluid accelerates to a very short distance at very high velocity of over
1000 km/h.
• Very high shear stress and cavitation forces disrupt the particles down to
submicron range.
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7. Research Question
Does the Bioavailability and Drug Loading of curcumin can be practically enhanced by
exploring it in the field of nanotechnology?
HYPOTHESIS
The bioavailability as well as the drug loading capacity of the curcumin can be enhanced by a
single technique i.e. Solid Lipid Nanoparticle Formulation.
 The method high pressure homogenization with ultrasonification is appropriate for the
formulation of the Curcumin SLNs.
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8. LITERATURE REVIEW
1. Preetha Anand et al have studied the Bioavailability of Curcumin, problems and
premises for their bioavailability. They found that Major reasons contributing to the low
plasma and tissue levels of curcumin appear to be due to poor absorption, rapid
metabolism, and rapid systemic elimination. They have also suggest various premises to
resolve these problems.
2. Preetha Anand et al Designed curcumin-loaded PLGA nanoparticles to enhance cellular
uptake and bioactivity of curcumin. Curcumin was encapsulated with 97.5% efficiency in
biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA)
and a stabilizer polyethylene glycol (PEG)-5000. In mice, curcumin (NP) was more
bioavailable and had a longer half-life than curcumin. Overall they demonstrate that
curcumin-loaded PLGA nanoparticles formulation has enhanced cellular uptake, and
increased bioactivity.
3. A. Pavan Kumar Reddy et al have gave a modern review on solid lipid nanoparticles in
which they mentioned about to the advantages, preparations and various other
information necessary to predict that the technique has ability to enhance the drug loading
capacity.
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9. Cont…
4. Sathish Sundar Dhilip Kumar et al performed Synthesis and characterization of
curcumin loaded polymer/lipid based nanoparticles and evaluation of their antitumor
effects on MCF-7 cells. The C-SLNs exhibited the mean particle size in the range of 184
nm with no aggregation. The surface charge of the material was around −29.3 mV.
Thermal studies (TGA) and surface chemistry studies (FT-IR 25 XRD) showed the
existence of drug curcumin in C-PSA-NPs. They conclude that the C-PSA-NPs are the
effective and potential alternative method for the tumour treatment of MCF-7 cell line.
5. Sanju Dhawan et al has done the Formulation development and systematic optimization
of solid lipid nanoparticles of quercetin for improved brain delivery. The optimized
formulation exhibited a particle size of less than 200 nm, 85.73% drug entrapment
efficiency and a zeta potential of 21.05 mV. The studies demonstrated successful targeting
of the potent natural antioxidant, quercetin, to brain as a novel strategy having significant
therapeutic potential to treat Alzheimer’s disease.
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10. 6. Dong Zhi Hou et al have produce and characterize of solid lipid nanoparticles (SLNs). The
high shear homogenization and ultrasound techniques were employed to produce solid lipid
nanoparticles (SLNs). Model drug mifepristone had been incorporated in SLNs. The mean
particle size measured by laser diffractometry (LD) was found to be 106nm with a narrow
particle distribution of polydispersity index, 0.278. Differential scanning Calorimetry and
X-ray diffraction measurements suggested that the majority of the SLNs were less
ordered arrangement of crystals, and this was favourable for increasing the drug
loading capacity. The drug entrapment efficiency (EE %) of SLNs was more than 87
percent and showed relatively long-term physical stability.
7. Waree Tiyaboonchai et al have formulate and characterize of curcuminoids loaded solid
lipid nanoparticles. solid lipid nanoparticles (SLNs) have been successfully developed using
a microemulsion technique at∼75 ◦C. mean particle size of ∼450 nm and a polydispersity
index of 0.4. Up to 70% (w/w) curcuminoids incorporation efficacy was achieved.
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11. AIM & OBJECTIVE
AIM:-To enhance the Bioavailability as well as the drug loading capacity of curcumin
simultaneously by Solid Lipid nanoparticles formulation.
Objective:- a.) To optimize and formulate the curcumin loaded SLNs by using High pressure
homogenization technique.
b.) Effect of Compritol on the Particles when applied into High pressure
homogenization technique.
c.) To investigate the effect of lipid state, on the particle size of the formulation.
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12. DRUG PROFILE
Curcumin is a Diarylheptanoid. It is the principal curcumanoid of turmeric, which is a
member of the ginger family (Zingeberaceae.).
Synonyms: - Indian saffron
Chemical name: - 1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione.
Molecular Structure:-
Molecular Formula: - C21H20O6
Molecular Weight: - 368.39
Melting point: - 183 °C (361°F; 456 K)
Solubility profile: - Curcumin is soluble in oil, and alkali, practically insoluble in water,
acidic and neutral pH. 12

13. Polymer profile
COMPRITOL 888.
Non-proprietary Names :
BP: Glycerol Dibehenate
Eur: Glycerol Dibehenate
USP-NF: Glyceryl Behenate
Synonyms: Compritol 888 ATO; 2,3-dihydroxypropyl docosanoate; docosanoic acid, 2,3-
dihydroxypropyl ester; E471; glycerol behenate; glyceroli dibehenas; Glyceryl
monobehenate.
Chemical Name : Docosanoic acid, monoester with glycerin
CAS Number: 30233-64-8
Melting point: 69-740C
Molecular Weight:1059.7
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14. GLYCERYL MONO STEARATE
Synonyms: 2,3-Dihydroxypropyl octadecanoate
CAS Number: 123-94-4
Melting point: 58 to 59 °C
Molecular Weight: 358.56 g/mol
Molecular formula: C21H42O4
Applications in Pharmaceutical Formulation or Technology
1. GMS is a food additive used as a thickening, emulsifying, anti-caking, and preservative
agent.
2. It provide a protective coating for hygroscopic powders.
3. A solidifier and control release agent in pharmaceuticals and a resin lubricant.
4. It is also used in cosmetics and hair care products.
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15. Poloxamer 188
. Synonyms: Lutrol ,Kolliphor 188, pluronic, polyethylene-propylene glycol copolymer
 Appearance: Crystalline white powder
 Molecular formula: HO(C2H4O)a(C3H6O)b(C2H4O)aH
 Molecular weight: 7680-9510 g/mol
 CAS Number:[9003-11-6]
 Melting point: 52-570C
 Functional Category : Dispersing agent; emulsifying and co-emulsifying agent
,solubilising agent
 Applications in Pharmaceutical Formulation or Technology
1. In pharmaceutical they are used as emulsifying or solubilising agent. The
polyethylene segment is hydrophilic while the polyoxypropylene segment is
hydrophobic.
2. Used as a wetting agent in ointments, suppository bases and gels. 15

16. PLAN OF WORK
1. Selection of problem
2. Review of Literature with respect to problem
3. Preformulation study
A. Authentication of drug:- i) Organoleptic properties.
ii)Melting point determination
iii) ATR Spectrum
iv) UV-Spectrometric analysis.
v) DSC
B. Drug excipient Compatibility study:- i) DSC
ii) ATR Spectrum
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17. 4. Optimized formulation of the C-SLNs with high shear homogenization.
5. Lyophilization of the preparation
6. Characterization:-
i) Particle size, PDI, Zeta potential.
ii) Entrapment Efficiency.
iii) DSC.
iv) XRD.
v) In-vitro drug release.
vi) Stability study.
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18. EXPERIMENTAL SECTION
1. Preformulation Study:-
a.) Organoleptic properties.
b.) Melting point:- Capillary method
c.) ATR Spectra:-
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19. RESULTS
1. Organoleptic Characteristic:-
2. Melting point:-
S.NO. PARAMETER OBSERVED REPORTED
1. Colour Yellow- orange Yellow-orange
2 Odour characteristic Characteristic
3 Appearance Crystalline Crystalline powder
S.no. Materials Observed(OC) Reported(OC)
1. Curcumin 171-172 170
2. Compritol 72-74 69-75
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20. 3. ATR Spectrum
• DRUG (Curcumin):-
Remarks Peak
sReported
Peak (cm-1)
Observed
O-H (Stretch) 3600-3200
=C-H (Stretch) 3095-3010 2997.19
C=O (Stretch) 1760-1690 1750.81
C=C (alkene) 1680-1600 1600.88
C-O (Stretch) 1450-1325 1325.23
C-O (Stretch) 1300-1050 1258.47
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21. Polymers
1. Compritol:-
Sr.
no
Functional groups Reported
values
Observed
values
1 -O-H(stretch) 3200-3700 3384.85
2 -COOH(saturated) 1710 1710.83
3 -C=C(mono
substituted benzene)
700-750 700.42
4 CH2 (methyl) 2870 2885.41
5 -C-O-C(esters) 1100-1300 1168.20
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22. 2. Glyceryl mono stearate:-
Sr
no
Functional
groups
Reported
values
Observed
values
1 -O-H(primary
alcohol)
1040-1060 1058.34
2 -C=C 1600-1625 1618.03
3 -NH2 3400-3500 3433.03
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23. 3. Poloxamer 188:-
Sr.
no
Functional
groups
Reported
values
Observed
values
1 -O-H(secondary
alcohol)
~1100 1084.95
2 p- disubstituted
benzene
800-860 826.27
3 Disubstituted
alkynes
2190-
2260
2199.83
4 C-CH 3020 3035.38
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24. References
• A. Pavankumar Reddy*, S. Parthiban, A. Vikneswari, G. P. Senthil kumar. A modern
review on solid lipid nanoparticles as novel Controlled drug delivery system. International
Journal of Research in Pharmaceutical and Nano Sciences. 2014;3(4):313 – 325
• Preetha Anand, Ajai kumar, B. Kunnumakkara, Robert A et al. Bioavailability of Curcumin:
Problems and Promises. Molecular pharmaceutics.2007;4(6):807–818.
• Shing Fung Chow Ka Yee Wana, Kwok Kin Cheng et al. Development of highly stabilized
curcumin nanoparticles by flash nanoprecipitation and lyophilization. European Journal of
Pharmaceutics and Biopharmaceutics. 2015:1-14.
• Sathish Sundar Dhilip Kumar, Ayyavu Mahesh, Surianarayanan Mahadevan, Asit Baran
Mandal. Synthesis and characterization of curcumin loaded polymer/lipid based
nanoparticles and evaluation of their antitumor effects on MCF-7 cells. Biochimica et
Biophysica Acta.2014:1-10.
• J. Shaikh, D.D. Ankola, V. Beniwal, D. Singh, M.N.V. Ravi Kumar.Nanoparticle
encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared
to curcumin administered with piperine as absorption enhancer.European Journal of
Pharmaceutical Sciences.2009;37:223–230
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