Nanostructured lipid carriers (NLC)

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Nanostructured lipid carriers (NLC)

  1. 1. 02 April 2013 Seminar onNanostructured Lipid Carriers for Topical Drug Delivery SystemPresented by: Guided by:Mr. Sachin S. Mali Dr. A. A. HajareM.Pharm. (IInd Semester), Professor and Head,Dept. of Pharm.Technology. Dept. of Pharm.Technology.BHARATI VIDYAPEETH COLLEGE OF PHARMACY, KOLHAPUR. 1
  2. 2. »AbbreviationsNLC- Nanostructured Lipid CarrierSLN- Solid Lipid NanoparticlesHPH- High Pressure HomogenizationNSAID- Non Steroidal Anti Inflammatory DrugLD- Laser DiffractometryGRAS- Generally Recognized As SafePI- Polydispersity Index 2
  3. 3. » Ways to Go» Introduction» Excipients used in NLC» NLC Techniques » High pressure homogenization» Mechanism of topical application» Characterization» Applications» Conclusion» Reference 3
  4. 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. 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. 5
  6. 6. »Types of NLC 6
  7. 7. » Objectives of NLCTo 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%. 7
  8. 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 8
  9. 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 9
  10. 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 10
  11. 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. 11
  12. 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 12
  13. 13. » High pressure homogenizationTechniques 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. 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. 14
  15. 15. » Cont… 15
  16. 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. 16
  17. 17. »Mechanism of topical application of NLC 17
  18. 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. 18
  19. 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 19
  20. 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). 20
  21. 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. 21
  22. 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). 22
  23. 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. 23
  24. 24. Marketed formulations 24
  25. 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. 25
  26. 26. »References DH McDanial, BA Neudeker, JC DiNardo, JA Lewis II and HI Maibach., Clinical efficacy assessment in photodamaged skin of 0.5% and 1.0% Idebenone,J.Cosm. Dermat. 4 (2005) 167- 173. Q.Xia,A. Saupe, R.H.Muller, Nanostructured lipid carrier as novel carrier for sunscreen 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 during reperfusion after cerebral ischemia, J. Pharmacol. Exp. Ther. 274(1995)1167–73. 26
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