July 24, 2017 | Autor: Editor Ijips | Categoria: Pharmaceutical Analysis
Share Embed

Descrição do Produto

eISSN: 2320-1428

Int.J.Inv.Pharm.Sci.,1(1)2013;81-84 www.ijips.net


ShriVishnu College of Pharmacy, Bhimavaram 2 Eisai pharmatechnologyvizag, 3 Hetero Drugs, 4 Narayana pharmacy college Nellore,

Accepted On: 28thJanuary 2013

For correspondence: [email protected]

ABSTRACT: Solid lipid nanoparticles (SLN) are rapidly developing colloidal drug delivery systems in the field of nanotechnology. Due to their unique sizedependent properties, lipid nanoparticles offer the possibility to develop new therapeutics. An incorporation of drugs into these nanocarriers offers drug targeting. Hence, there is a tremendous research is going on SLN toreach the goal of controlled and site specific drug delivery. In this article we focused on advantages, different preparation methods which are suitable for large scale production, evaluation and application of SLNs. Key Words: Solid lipid nanoparticles, homogenization, microscopy, targeting.

INTRODUCTION: Colloidal carriers ranging in size between 10 and 1000 nm are


known as nanoparticles.They are manufactured from natural or

Controlled and site specific drug delivery

synthetic polymers and ideally suited to optimize drugdelivery and

Good biocompatible

reduce toxicity. The scarcity of safe polymers with regulatory

More sensible for higher drug loading

approval and their high cost have limited application of

Improve the stability of bioactive compounds

nanoparticles toclinical medicine. To overcome these limitations of

Enhance the bioavailability of entrapped pharmaceuticals

polymeric nanoparticles, lipids have been put forward as an

Chemical protection of bioactive compounds

alternative carrier, particularly for poorly water soluble drugs.

Easy to scale up and sterilize

These lipid nanoparticles areknown as solid lipid nanoparticles.In order to overcome the disadvantages associated with the liquid state

Production of SLNs:

of the oil droplets, the liquidlipid was replaced by a solid lipid,

SLNs are prepared using lipid, emulsifier and water/solvent by


employing various methods like



transformed colloidal







composed of solid hydrophobic core having a monolayer coating of


High pressure homogenization.

phospholipids.Solid lipid nanoparticles (SLN) introduced in 1991


Hot homogenization.

represent an alternative carrier system totradition colloidal carriers


Cold homogenization.

such as - emulsions, liposomes and polymeric micro and



Unique Properties of SLN:

Emulsification methods a)

Micro emulsion method


Double emulsion method


Ultrasonication or high speed homogenization. Precipitation method

Small size


Large surface area


Spray drying method

High drug loading


Supercritical fluid method

Their potential to improve performance of

1. High pressure homogenization


High pressure homogenization technique is very efficient for the


Page | 81

production of SLNs. This method is easy to handle. High pressure

homogenizers push a liquid with high pressure (100–2000 bar)

by stirring the lipid and an aqueous emulsifier solution at high

through a narrow gap. The fluid accelerates on a very short

speed and high temperature conditions. Finally SLNs are produced

distance to very high velocity (over 1000 Km/h). Very high shear stress and disrupt the particles down to the submicron

by dispersing the warm w/o emulsion in an aqueous stabilizer

range.generally this method is divided into hot and cold

solution (w/o/w) at 2-30C under high speed stirring conditions.

homogenization. 3. Ultrasonication or high speed homogenization: 1a) Hot homogenization: Hot homogenization is carried out at

It is very simple and it can be advantageous over other method

temperatures above the melting point of the lipid. First

like hot and cold homogenization because the equipment used in

disperse/dissolve drug in the melted lipid and then add this mixture

this technique is very common in every lab. The main drawbacks

to the hot aqueous surfactant solution using stirring device. The

of this method are broader particle size distribution, particle

obtained pre emulsion is homogenized at higher pressure to get hot

growth upon storage and contamination of metal due to

o/w nanoemulsion. Finally SLNs after cooling of above solution to


room temperature. In most cases 3-5 homogenization cycles at 5001500 bar are sufficient8. Increasing the homogenization leads to an

4. Precipitation method :The glycerides are dissolved in an

increase of the particle size due to particle coalescence which

organic solvent (e.g. chloroform) and the solution will be

occurs because of the high kinetic energy of the particles. The main

emulsified in an aqueous phase. After evaporation of the organic

drawbacks of this method is High temperature lead to degradation

solvent the lipid will be precipitatedforming nanoparticles. The

of active compound and Partitioning and hence loss of drug into the

main disadvantage is need of an organic solvent

aqueous phase during homogenization. 5. Spray drying method: 1b) Cold homogenization: Cold homogenization has been

It is a cheaper procedurethan lyophilization to prepare SLNs. This

developed to overcome various problems associated with hot

method cause particle aggregation due to high temperature, shear

homogenization. First disperse/dissolve drug in the melted lipid and

forces and partial melting of the particle. The best result was

solidif9ied the mixture using liquid nitrogen/dry ice. The solidified

obtained with SLN concentration of 1% in a solution of trehalose

mixture grinded to fine particles using powder mill and this is

in water or 20% trehalose in ethanol-water mixtures (10/90 v/v)

disperse in a cold surfactant solution using stirrer. The obtained pre suspension is homogenized at higher pressure and at below room

6. Supercritical fluid method:

temperature to get SLNs. Compared to hot homogenization; larger

This is a new method and advantage of solventless technique.

particle sizes and a broader size distribution is typical of cold

SLNs can be prepared by the rapid expansion of supercritical

homogenized samples. Cold homogenization minimizes the thermal

carbon dioxide (99.99%) solutions


exposure of the sample . EVALUATION OF PREPARED SLNS: 2a) Micro emulsion method: This method is based on the dilution of microemulsions. As micro-emulsions are two-phase systems

1. Entrapment efficiency

composed of an inner (disperse phase) and outer phase (continuous

2. In Vitro assessment of drug release from SLNs

phase).The transparent system obtained by adding a mixture of

3. Analytical characterization of SLNs

water, emulsifier, co- emulsifier to the melted lipid at higher

A)Particle size and zeta potential

temperature under mild stirring condition. The hot micro emulsion

B)Surface element analysis


is dispersed in cold water (2-3 ) under stirring.Typical volume

4. stability of SLNs

ratios of the hot micro emulsion to cold water are in the range of 1:25 to 1:50.

1. Entrapment efficiency: It influences the release characteristics of drug from SLNs.

2b) Double emulsion method:It is a novel method for the

The amount of drug encapsulated per unit weight of SLNs is

production of hydrophilic loaded SLNs.W/O emulsion is obtained

determined after separation of the entrapped drug from the

Page | 82

SLN formulation. This separation can be carried out using the

particles is collected and fit into fundamental

different techniques like ultracentrifugation and centrifugation

primary variable.

filtration. 2.


In vitroAssessment of drug release from SLNs:

Dynamic Light Scattering(DLS): DLS, also known as PCS or quasi-elastic light scattering (QELS)

Dialysis tubing: In vitro drug release can be carried out using

records the variation in the intensity of scattered

dialysis tubing. The solid lipid nanoparticles dispersionis

light on the microsecond time scale. The advantages

placed in pre - washed dialysis tubing which can be

of the method are the speed of analysis, lack of

hermetically sealed. The dialysis sac then dialyzedagainst a


suitable dissolution medium at room temperature; the samples

micrometer particles.

are withdrawn from the dissolutionmedium at suitable







Acoustic Spectroscopy: It measures the attenuation

intervals, centrifuged and analyzed for the drug content using a

of sound waves as a means of determining size

suitable analyticalmethod.

through the fitting of physically relevant equations.



Surface elemental analysis:It is characterized by using different techniques like Electrophoresis and Laser Doppler anemometry.


Particle size and zeta potential:


Photon Correlation Spectroscopy: Also known as



dynamic light scattering method. This technique

The physical properties of SLN’s during prolonged storage can be

measures the fluctuation of the intensity of the

determined by monitoring changes in zeta potential, particle size,



drug content, appearance and viscosity as the function of time.

movement. PCS is a good tool to characterize

External parameters such as temperature and light appear to be of

nanoparticles, but it is not able to detect larger micro

primary importance for long – term stability. The zeta potential


should be in general, remain higher than -60mV for a dispersion to










remain physically stable.

microscopy (SEM) and Transmission electron microscopy (TEM) are the direct method to measure nanoparticles,




nanoparticles with the former method being used for



Page | 83

An adjuvant for vaccines: Adjuvants are used in vaccination to enhance the immune response. Being in

Atomic Force Microscopy (AFM): A probe tip

the solid state, the lipid components of SLNs will be

with atomic scale sharpness is rastered across a

degraded more slowly providing a longerlasting exposure

sample to produce a topological map based on forces

to the immune system. 2.

As Targeted anticancer drug carriers: Tumor targeting

Differential Scanning Calorimetry (DSC): DSC

has been achieved with SLN loaded with drugs like

can be used to determine the nature and speciation of

methotrexate, Tamoxifen and camptothecin.

crystallinity within nanoparticles. 5.


morphological examination.

at play between the tip and the surface. 4.



To deliver the proteins and peptides: Proteins and

Nuclear Magnetic Resonance (NMR): NMR is

antigens intended for therapeutic purposes may be

used to determine both size and nature of

incorporated or adsorbed onto SLN, and further


administered by parenteral routes or by alternative routes (SLS)/Fraunhofer

such as oral, nasal and pulmonary. A, insulin, calcitonin

Diffraction: The method is fast and rugged. In this

and somatostatin have been incorporated into solid lipid

method the light scattered from a solution of

particles and are currently under investigation.





As targeted brain drug delivery: SLNs can improve the ability of the drug to penetrate through the BBB and is a promising drug targeting system for the treatment of CNS disorders.


As gene vector carrier: There are several recent reports of SLN carrying genetic/peptide materials such as DNA, plasmid DNA and other nucleic acids.


As cosmeceuticals:The SLNs have been applied in the sunscreen preparations and as an active carrier agent for molecular sunscreens and UV blockers.


For potential agriculture application: Essential oil extracted from ArtemisiaarboreseensL when incorporated in SLN, were able to reduce the rapid evaporation comparedwith emulsions and the systems have been used in agriculture as a suitable carrier of ecologically safe pesticides.

CONCLUSION: Solid lipid nanoparticles are combining the advantage of other colloidal drug carriers and rectify the disadvantages of them. SLNs have the potential to achieve, at least partially, these broad objectives. Apart from these, the regular objective of controlled drug delivery is aptly achieved with SLNs.Clear advantages of SLN include the composition (physiological compounds), the rapid and effective production process including the possibility of large scale production, the avoidance of organicsolvents and the possibility to produce carriers with higher encapsulation efficiency . Hence, in the future we can expect more patented dosage forms in the form of SLNs.

REFERENCES: 1. Vobalaboina Venkateswarlu, Manjunath, Preparation, Characterization and in vitro release kinetics of clozapine solid lipid nanoparticles, Journal of controlled release, 95, (2004);627638. 2. DongzhiHou, Chanagshegxie,The production and characterstics of solid lipid nanoparticles, Biomaterials, 24,(2003);1781-1785.

Page | 84

3. Hou Jun, Zhou shit wen, New resarch on development of solid lipid nanoparticles, Journal of medical college of PLA, 11,(2007); 385-390. 4. Vishvajit A. Kamble, Deepali M. Jagdale And VilasraoJ.Kadam, Solid Lipid Nanoparticles As Drug Delivery System, International Journal of Pharma and Bio Sciences, 1, (2010);1-9. 5. Cavalli R, Marengo E, Rodriguez L, Gasco MR.,Effects of some experimental factors on the production process of solid lipid nanoparticles, Eur J Pharm Biopharm, 43, (1996); 110-115. 6. Andrew Loxley, PhD, Solid Lipid Nanoparticles for the Delivery of Pharmaceutical Actives, Drug Delivery Technology, 9, (2009). 7. Ramesh Reddy Putheti, R N Okigbo, Madhusoodhan Sai Advanapu And SangeetaChavanpatil, Nanotechnology importance in the pharmaceutical industry, African Journal of Pure and Applied Chemistry,2,(2008); 027-031. 8. Miglietta, A., R. Cavalli, C. Bocca, L. Gabriel andM.R. Gasco, Cellular uptake and cytotoxicityof Solid Lipid Nanospheres (SLN) incorporatingdoxorubicin or paclitaxel. Int. J. Pharm., 210: 61-67. 9. P. Ekambaram, A. Abdul HasanSathaliAnd K. Priyanka, Solid Lipid Nanoparticles: A Review, scientific reviews and chemical communications, 2, (2012);80-102. 10. Nagi A. ALHaj, Rasedee Abdullah, Siddig Ibrahim and Ahmad Bustamam, Tamoxifen Drug Loading Solid Lipid Nanoparticles Prepared by Hot High Pressure Homogenization Techniques, American Journal of Pharmacology and Toxicology 3, (2008); 219-224. 11. S. Mukherjee, S. Ray And R.S. Thakur, Solid Lipid Nanoparticles: A Modern Formulation Approach In Drug Delivery System Ind. J. Pharm. Sci., 5,(2009);349-358. 12. Lai F, Wissing SA, Muller RH, Fadda AM. Artemisia arborescens L essential oil-loaded solidlipid nanoparticles for potential agriculture application: preparation and characterization.AAPS Pharm SciTech., 71, (2006);349–358. 13. Mehnert, W. and K. Mader, Solid lipidnanoparticles production, characterization andapplications. Advanced Drug Delivery Review, 47, (2001); 165-196. 14. Muller, H., K. Mader and S. Gohla, SolidLipid Nanoparticles (SLN) for controlled drugdelivery-a review of the state of the art. Eur. J.Pharm. Biopharm., 50, (2000); 161-177. 15. Murthy RSR., Solid lipid nanoparticles as carriers for anticancer drugs to solid tumours.,DrugDelivery, 12, 2005;385-392. 16. Ugazio, E., R. Cavalli and M.R. Gasco,Incorporation of cyclosporinA in Solid LipidNanoparticles (SLN). Int. J. Pharm., 5, (2000); 341-344. 17. AL-Haj, N. and A. Rasedee, Solid lipid nanoparticles preparation and characterization. Int.J. Pharmacol., 4, (2008); 1-4.

Lihat lebih banyak...


Copyright © 2017 DADOSPDF Inc.