Why SLN ?Conventional o/w emulsionprotection of drug against chemical degradation is required. Hence,Incorporation of drug in the solid lipid matrix surely offer a betterprotection.Prolonged release of drug from emulsion is not feasible which can beachieved to a certain extent from SLN.Polymeric nanoparticles:Lower cytotoxicity of SLN due to the absence of solvents.Low cost of excipients.Large scale production is possible by the simple process of high-pressure homogenization
In comparison with liposomes SLNs offer better protection to drugagainst chemical degradation. However there are certain limitations associated with SLN, likelimited drug loading capacity and drug expulsion during storage,which can be minimized by the next generation of solid lipids,Nanostructured lipid carriers (NLC). NLC are lipid particles with a controlled nanostructure thatimproves drug loading and firmly incorporates the drug duringstorage .Owing to their properties and advantages, SLN and NLC may findextensive application in topical drug delivery, oral and parentaladministration of cosmetic and pharmaceutical actives.Cosmeceuticals is emerging as the biggest application target of
PREPARATION OF SLNs• SLNs are made up of solid lipid, emulsifier and water/solvent.• The lipids used: triglycerides (tri-stearin), partial glycerides(Imwitor), fatty acids (stearic acid, palmitic acid), steroids (cholesterol) and waxes (cetyl palmitate).(Imwitor is blend of mono, di and tri-glycerides especially of capryllicand caproic acids.)• Various emulsifiers and their combination (Pluronic F 68, F 127) have been used to stabilize the lipid dispersion. The combination of emulsifiers might prevent particle agglomeration more efficiently and hence helps in dispersion.(pluronic f 123 is triblock co polymer of polyethylene glycol andpropylene glycol)
Preparation methods:-1. High shear homogenization:• Used for the production of solid lipid nanodispersions• Method is easy to handle. Dispersion quality is often compromised by the presence of micro particles.• Different parameters which affect the process include emulsification time, stirring rate and cooling condition & also the particle size are investigated by Olbrich et al.• Lipids: tripalmitin, mixture of mono, di, triglycerides (WitepsolW35) with glycerol bahenate and poloxamer 188 used as steric stabilizers or emulsifiers (0.5% w/w). Witepsol W35 on dispersion, the best SLN quality was obtained after stirring for 8 min at 20,000 rpm followed by cooling 10 min and stirring at 5000 rpm at a room temperature.Higher stirring rates did not significantly change the particle size, but slightlyimproves the Dispersion.
2. Hot homogenization:• Carried out at temperature above the melting point of the lipid and is similar to homogenization of emulsion• Typically lipid content is between 5-10%. By this method up to 40% success is obtained. A pre-emulsion of the (drug loaded) lipid melt and the aqueous emulsifier phase (same temperature) is obtained by high- shear mixing device.• High pressure homogenization of the pre-emulsion is done above the lipid melting point.• The quality of the pre-emulsion affects the quality of the final product to a great extent and it is desirable to obtain droplets in the size range of a few micrometers.
• Lower particle sizes are obtained at higher processing temperatures due to lower viscosity of the lipid phase. Good product is obtained due to several passes through the high-pressure homogenizer (HPH), typically 3-5 passes.• High pressure processing always increases the temperature of the sample. In most cases 3-5 homogenization cycles at 500-1500 bar are sufficient. Problem: High temp. may lead to degradation of the active compound.
3. Cold homogenization:• This method has been developed to overcome the problems of the hot homogenization technique such as: Temperature mediated accelerated degradation of active compound.• First step in between cold and hot homogenization is same but they are differing from next steps. The lipid melt is cooled rapidly using ice or liquid nitrogen (for distribution of drug in the lipid matrix).• Particle sizes attained are in the range 50-100 microns. Compared to hot homogenization; larger particle sizes and a broader size distribution are typical of cold homogenized samples.• Cold homogenization minimizes the thermal exposure of the sample.
4. Ultrasonication or high speed homogenization:• SLNs can also be produce by sonication or high speed stirring.• It is very simple and it can be advantageous over other method like hot and cold homogenization because the equipment used in this technique is very common in every lab.• Disadvantage is non uniform size distribution and physical instability of active compound like particle growth upon storage and also metal contamination due to ultrasonication.
6. SLN prepared by solvent emulsification/evaporation: (mostlyconsidering drug delivery)• The lipophilic material is dissolved in water immiscible organic solvent (cyclohexane) that is emulsified in an aqueous phase. Upon evaporation of the solvent nanoparticle, dispersion is formed by precipitation of the lipid in the aqueous medium.• The mean diameter of the obtained particles was 25 nm with cholesterol acetate (as a model drug) and lecithin/sodium glycocholate blend as emulsifier.• The reproducibility of the result was confirmed by Siekmann et.al. , who produced the cholesterol acetate nanoparticles of mean size 29 nm.
Manufactured By -• m K Nano• PharmaSol• Kemeria Group
REFERENCES• Solid Lipid Nanoparticles: A Modern Formulation Approach in Drug Delivery System S. MUKHERJEE*, S. RAY AND R. S. THAKUR• Solid Lipid Nanoparticles: Technological Developments and in Vivo Techniques to Evaluate Their Interaction with the Skin Mariella Bleve, Franca Pavanetto and Paola Perugini Department of Drug Sciences, University of Pavia• SOLID LIPID NANOPARTICLES AS COLLOIDAL DRUG CARRIER SYSTEMS António J. Almeida