Nanostructured lipid carriers (NLCs) were presented as a topical drug delivery system. NLCs consist of a blend of solid and liquid lipids which can incorporate drugs at high loading capacities. They were summarized to have advantages over solid lipid nanoparticles including avoidance of drug expulsion and unpredictable gelation. Methods for producing NLCs like high pressure homogenization were described. NLCs were said to increase skin permeation of drugs while providing occlusive and moisturizing properties beneficial for skin care. Several drug-loaded NLC formulations were presented including ones for flurbiprofen, minoxidil, and tacrolimus to improve their topical delivery and stability.

1. 02 April 2013
Seminar on
Nanostructured Lipid Carriers for Topical Drug Delivery System
Presented by: Guided by:
Mr. Sachin S. Mali Dr. A. A. Hajare
M.Pharm. (IInd Semester), Professor and Head,
Dept. of Pharm.Technology. Dept. of Pharm.Technology.
BHARATI VIDYAPEETH COLLEGE OF PHARMACY, KOLHAPUR.
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2. »Abbreviations
NLC- Nanostructured Lipid Carrier
SLN- Solid Lipid Nanoparticles
HPH- High Pressure Homogenization
NSAID- Non Steroidal Anti Inflammatory Drug
LD- Laser Diffractometry
GRAS- Generally Recognized As Safe
PI- Polydispersity Index
2

3. » Ways to Go
» Introduction
» Excipients used in NLC
» NLC Techniques
» High pressure homogenization
» Mechanism of topical application
» Characterization
» Applications
» Conclusion
» Reference
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4. » Introduction
» NLC which are second generation of SLN.
» NLC composed of binary mixture of solid lipid and a spatially different
liquid lipid as hybrid carrier.
» Average size between 10-500 nm.
4

5. »NLC hybrid carriers
» NLC consist of a mixture of specially blended solid lipid (long
chain) with liquid lipid (short chain), preferably in a ratio of 70:30
to 99.9:01.
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6. »Types of NLC
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7. » Objectives of NLC
To overcome disadvantages of SLN such as
Tendency for particle growth.
Unpredictable gelation tendency.
Poor drug loading capacity.
Drug expulsion after polymeric transition during storage.
High water content in dispersions have been observed i.e.70-99.9%.
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8. »Excipients used in NLC
 Solid lipids
A mixture of several chemical compounds which have high melting point
(higher than 40ºC).
These solid lipids are well tolerated of GRAS status.
Accepted for human use.
Also in vivo biodegradable.
Examples-
» Beeswax
» Carnauba wax
» Dynasan
» Precifac
» Stearic acid
» Apifil
» Cutina CP
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9. » Cont...
 Liquid lipids (OIL)
These solid lipids are well tolerated of GRAS status.
Accepted for human use.
Examples-
» Cetiol V
» Miglyol
» Castor oil
» Oleic acid
» Davana oil
» Palm oil
» Olive oil
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10. » Cont...
 Emulsifying agents
It is an surfactant, which is adsorbed at interfaces and lowers the interfacial
tension.
When a surfactant is present in small amounts, it enhances its colloidal
stability by decreasing either or both of the rates of aggregation.
Examples-
» Miranol ultra
» PlantaCare
» Tween 80
» Plaronic F68
» Polaxamer 188
» Phospolipon 90G
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11. » Cont...
 UV blockers
Help to protect the skin from the ultraviolet radiation of the sun.
Lowering the risk of skin cancer.
Sunscreen products contain either an organic chemical compound that absorbs
UV light.
Examples-
Avobenzone :- Absorb UV-A radiation (maximum absorption at 357 nm)
Butyl methoxydibenzoylmethane
 Aquaous medium
The water used in all experiments was purified water by reverse osmosis.
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12. » NLC Techniques
High pressure homogenization
Micro emulsion technique
Solvent emulsification evaporation technique
Solvent displacement technique
Solvent diffusion method
Phase inversion
Melt Emulsification
Simple sonication method
Lyophilization
Spray drying method
Solvent evaporation method
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13. » High pressure homogenization
Techniques of HPH
 Hot HPH technique
 Cold HPH technique
 Hot HPH
Lipid and drug are melted (10oC above the melting point of the lipid) and
combined with an aqueous surfactant solution at the same temperature.
A hot pre-emulsion is formed by high shear device (e.g. using Ultra-Turrax).
The hot pre‐emulsion is then processed in a temperature controlled high
pressure homogenizer at 500 bar using piston gap homogenizer.
The obtained nanoemulsion recrystallizes upon cooling down to room
temperature forming NLC.
13

14. » Cont…
 Cold HPH
Suitable for processing heat-labile drugs or hydrophilic drugs.
Lipid and drug are melted together and then rapidly ground under liquid
nitrogen forming solid lipid micro particles.
A pre‐suspension is formed by homogenisation of the particles in a cold
surfactant solution.
This pre‐suspension is then further homogenised in a HPH at or below room
temperature at predetermined homogenisation conditions to produce NLC.
Both HPH techniques are suitable for processing lipid concentrations of up to
40% and generally yield very narrow particle size distributions.
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15. » Cont…
15

16. » Cont…
Advantages
Avoidance of organic solvents.
Short production time.
Possibility of production on large scale.
Disadvantages of Hot HPH
High heating temperature promotes degradation of the
labile active compounds.
Surfactant have cloud point lower than 850C therefore
high temperature may reduce the emulsifying capacity
of the surfactants this effect induce the instability to the
NLC.
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17. »Mechanism of topical application of NLC
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18. » Benefits of topical application of NLC
Increase in skin occlusion and adhesiveness to skin.
Film formation, repair of stratum corneum.
Increase of skin hydration and elasticity.
Enhancement of skin permeation and drug targeting.
Enhancement UV protection system.
Enhancement of chemical stability of chemically labile
compounds.
i.e. skin healing, caring and protective effects.
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19. » Characterization
Morphology (size and shape)
» Scanning electron microscopy (SEM)
» Transmission electron microscopy (TEM)
» Photon correlation spectroscopy (PCS)
Zeta Potential Analysis
» Zetasizer
Degree of Crystallinity and Lipid Modification
» Differential scanning calorimetry (DSC)
» X-ray diffraction (XRD)
Determination of Viscosity
» Rheometer
Drug Content and Entrapment Efficiency
» Ultracentrifugation followed by quantitative analysis by HPLC
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20. » Cont...
In-vitro drug release study
Using Franz diffusion cell/ Keshary Chien diffusion cell and cellulose dialysis
membrane.
In-vitro skin penetration study
Using human cadaver skin/ wistar rats abdominal skin and Keshary chien
cell/modified Franz diffusion cell.
In-vitro skin occlusivity test
Prevention of water loss by the formulation will be studied. (De
Vringer, 1992, Wissing et al, 2001)
Primary skin irritation study
Will be carried out by using Draize patch test on rabbits.(Draize et
al, 1944, Verneer, 1991, Joshi and Patravale 2006).
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21. » Applications
» Topical NLC carrier gel of flurbiprofen
Upon oral administration abdominal discomfort along with other gastrointestinal
side effects.
It has a short elimination half-life of 3.9 hours.
Flurbiprofen NSAID is used to treat gout, osteoarthritis, rheumatoid arthritis, and
sunburn.
» Minoxidil loaded NLC based hydrogel formulation
The lipophilic characteristics of this drug implies that conventional topical
formulations.
Applications of such formulations may cause severe adverse reactions.
Minoxidil has been widely used for the topical treatment of alopecia.
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22. » Cont...
» Tacrolimus loaded NLC for topical drug delivery
The adverse effects of tacrolimus include transient burning, sensation, and
itching and having lower penetration profile.
Tacrolimus is a strong NSAID used for the management of atopic dermatitis.
» Miconazole nitrate loaded NLC improving the antifungal therapy
Poor dissolution and lack of absorption make it a poor candidate for oral
administration.
Miconazole nitrate (Bennett et al., 2001).
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23. Advantages
» Higher drug loading capacity.
» Physical and chemical stability avoids expulsion of drugs during storage.
» Carriers are composed of physiological and biodegradable lipid.
» Exhibiting low systemic toxicity and low cytotoxicity.
» The small size of lipid particles enhance drug flux through the skin.
» Controlled release from these carriers are possible.
» The overall solid content of NLC could be increased up to 95% .
» NLC can easily be incorporated in creams, lotion.
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24. Marketed formulations
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25. » Conclusion
NLC are the new generation of nanoparticulate active substance vehicles and are
attracting major attention as novel colloidal drug carriers for topical use.
NLC systems with good perspectives to be marketed very successfully, reason for
this is they were developed considering industrial needs, e.g. scale up, qualification
and validation, simple technology, low cost, regulatory excipient status (e.g.
GRAS), tolerability etc.
Today HPH represents an efficient pathway for production of NLC as novel systems
composed of physiological lipid materials suitable for topical, dermal administration
novel drug delivery system.
Nanostructured lipid carriers hold great promise for reaching the goal of controlled
and site specific drug delivery and hence attracted wide attention of researchers.
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26. »References
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assessment in photodamaged skin of 0.5% and 1.0% Idebenone,J.Cosm. Dermat. 4 (2005) 167-
173.
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formulations,Int.J.Cosmet.Sci.29(2007) 473-482.
M.S.Kortig, W.Mehnert, Lipid nanoparticles for improved topical application of drugs for skin
diseases, Advanced Drug Delivery Reviews.59(2007)427-433.
A.K.Verma,K.Sachin,Release kinetics from bio-polymeric nanoparticles encapsulating protein
synthesis inhibitor,Curr.Pharm.Biotechnol.6(2005)121-130.
M.K.Jain, Order and dynamics in bilayers and solute in bilayers,Introduction to Biological
Membranes, Wiley.12(1998) 122–165.
B.R.Shivakumar BR, V. Ravindranath, Glutathione and protein thiol homeostasis in brain
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