Solid Lipid Nanoparticles (SLNs) are a promising new drug delivery system that can overcome issues with solubility and stability of lipophilic drugs. SLNs are solid colloidal particles ranging in size from 100-1000nm that are composed of physiological lipids. They can incorporate both hydrophilic and hydrophobic drugs in either a homogeneous matrix or an enriched shell or core depending on production methods. SLNs have advantages over other nanoparticles in being biocompatible, physically stable, and able to provide controlled drug release over prolonged periods. However, challenges remain in fully controlling particle size, lipid crystallinity, and drug release kinetics.

1. Solid Lipid Nanoparticles: A
Drug Delivery Technology

2. ABSTRACT:
One of the situations in the treatment of disease is the delivery of
efficacious medication of appropriate concentration to the site of action in a
controlled and continual manner. Nanoparticle represents an important
particulate carrier system, developed accordingly. Nanoparticles are solid
colloidal particles ranging in size from 1 to 1000 nm and composed of
macromolecular material. Nanoparticles could be polymeric or lipidic (SLNs).
Industry estimates suggest that approximately 40% of lipophilic drug candidates
fail due to solubility and formulation stability issues, prompting significant
research activity in advanced lipophile delivery technologies. Solid lipid
nanoparticle technology represents a promising new approach to lipophile drug
delivery. Solid lipid nanoparticles (SLNs) are important advancement in this
area. The bioacceptable and biodegradable nature of SLNs makes them less
toxic as compared to polymeric nanoparticles. Supplemented with small size
which prolongs the circulation time in blood, feasible scale up for large scale
production and absence of burst effect makes them interesting candidates for
study. In this present review this new approach is discussed in terms of their
preparation, advantages, characterization and special features.
KEYWORDS: Nanotechnology; Colloidal carriers; Solid lipid nanoparticles;
Liposomes

3. Nanoparticles
•Nanoparticles are solid polymeric, submicronic colloidal system range between 5-300nm
consisting of macromolecular substances that vary in size 10nm to 1000nm. The drug of
interest is dissolved, entrapped adsorbed, attached or encapsulated into the nanoparticle
matrix Depending upon the method of preparation, nanoparticle, nanosphere or nanocapsule
can be obtained with different properties and release characteristics for the encapsulated
therapeutic agent. Nanosphere are matrix system in which drug is physically and uniformly
dispersed through out, then particles prepared by using different polymers such as
polyalkylcyanoacrylate & poly lactides or they can be solid lipid nanosphere prepared using
lipids like dipalmitoyl –phosphatidyl choline . Nanocapsule are ultrafine vesicular system with a
diameter less than 1 mcm in which the drug is confined to a cavity surrounded by a unique
polymer membrane and having aqueous or oily core containing drug substances.
Types of NPS as carrier for drug & diagnostic agents
• Polymeric NPS
• Nanosuspensions and nanocrystals
• Polymeric micelles
• Ceramic NPS
• liposome’s
• fullerenes and dendrimers
• SLNP (Solid lipid nanoparticles)
• Magnetic nanoparticles
• Nanoshells coated with gold
• Nanomers and carbon nanotubes

4. Solid lipid nanoparticles: Solid lipid nanoparticles are one of the novel potential colloidal carriers
systems in the range of 100-150nm as alternative materials to polymers which is identical to oil in water
emulsion for parenteral nutrition, but the liquid lipid of the emulsion has been replaced by a solid lipid. They
have many advantages such as good biocompatibility, low toxicity and lipophillic drugs are better delivered
by solid lipid nano particles and the system is physically stable. Solid lipid nanoparticles may be a promising
sustained – release and drug targeting system for lipophilic CNS antitumor drugs.
Types of solid nanoparticles
The types of SLNs depend on the chemical nature of the active ingredient and lipid, the solubility of actives
in the melted lipid, nature and concentration of surfactants, type of production and the production
temperature. Therefore 3 incorporation models have been proposed for study.
SLN, Type I or homogenous matrix model- The SLN Type I is derived from a solid solution of lipid and
active ingredient. A solid solution can be obtained when SLN are produced by the cold homogenation
method. A lipid blend can be produced containing the active in a molecularly dispersed form. After
solidification of this blend, it is ground in its solid state to avoid or minimize the enrichment of active
molecules in different parts of the lipid nanoparticles.
SLN, Type II or drug enriched shell model – It is achieved when SLN are produced by the hot technique,
and the active ingredient concentration in the melted lipid is low during the cooling process of the hot o/w
nanoemulsion the lipid will precipitate first, leading to a steadily increasing concentration of active molecules
in the remaining melt, an outer shell will solidify containing both active and lipid. The enrichment of the outer
area of the particles causes burst release. The percentage of active ingredient localized in the outer shell can
be adjusted in a controlled shell model is the incorporation of coenzyme Q 10.
SLN, Type III or drug enriched core model- Core model can take place when the active ingredient
concentration in the lipid melt is high & relatively close to its saturation solubility. Cooling down of the hot
oil droplets will in most cases reduce the solubility of the active in the melt. When the saturation solubility
exceeds, active molecules precipitate leading to the formation of a drug enriched core.

5. Preparation of solid lipid nanoparticles
 Solid lipid nanoparticles made from solid lipids or lipid blends, produced by high
pressure homogenation of melted lipids disperse in an aqueous as outer phase
stabilized by surfactants as Tween 80, sodium dodecyl sulphate, lecithin etc. High
pressure homogenation can produce particle dispersion with a solid content of 20-30%.
The drug loaded -lipid melt is dispersed in to surfactant solution to give a preemulsion.
 This preemulsion is passed through high pressure homogenizer to yield hot oil in water
emulsion which cools down. The lipid crystallizes and forms solid lipid nanoparticles.
The aqueous solid lipid nanoparticles dispersion can be incorporated in traditional in
dosage forms like tablets and pelletes, for producing pellet. The water for extrusion mass
is replaced by aqueous solid lipid nano particles dispersion . The pelletes disintegrate
and release the SLN completely non aggregated.
 Alternatively, they can be produce surfactants –free using steric stabilizers
(Poloxamer-188) or an or an outer phase of an increased viscosity (Ethyl cellulose
solution). Solid lipid nanoparticles can be transformed to a dry product by spray drying or
lyophillization. Solid lipid nanoparticles can also be produced in nano aqueous media
e.g. PEG 600 production in PEG-600 gives a dispersion which can be directly filled into
soft gelatin capsules

7. Electrolyte- and pH-stabilities of aqueous solid lipid
CHARACTERIZATION nanoparticle (SLN)
•The influence of artificial gastrointestinal (GI) media on
OF SLN PARTICLES the physical stability of solid lipid nanoparticle (SLN)
formulations consisting of different lipids and various
 In vitro and ex vivo surfactants/stabilizers have been investigated in vitro, with
respect to ionic strength and pH. Laser diffractometry and
methods for the zeta potential measurements were the techniques applied.
Some SLN formulations already showed
assessment of drug aggregation/particle growth in the presence of electrolytes
release from SLNs In vitro at neutral pH .
•Other lipid nanodispersions remained physically stable
drug release with respect to the influence of electrolytes, but were pH-
sensitive. It was possible to produce SLN that were GIT
 Dialysis tubing- (gastrointestinal tract) stable by an optimized stabilizer
composition.
 Reverse dialysis- • There is no optimal surfactant mixture for stabilization of
any lipid, e.g. SLN consisting of the lipid Cutina CP
 Franz diffusion cell- showed GIT stability in combination with the stabilizer
sugar ester S1670, whereas the stabilization with the
 Ex vivo model for surfactant mixture Tween 80/Span 85 was not effective.
Vice versa, the emulsifier Pluronic F68 stabilized the lipid
determining permeability Compritol ATO 888 but not the lipid Imwitor 900
sufficiently to avoid aggregation of the SLN dispersion in
across the gut artificial GI media. The stabilizing properties depend
obviously on the specific interactions of the lipid matrix
with the emulsifier, e.g. anchoring of the stabilizer on the
lipid surface and density on the surface.

8. Advantages of Solid lipid Nanoparticle
•• The solid matrix provides highest flexibility in Solid Lipid Nanoparticle Stability
controlling the release profile. The slower
degradation velocity in vivo (e.g. compared to Lipid nanoparticle stability must be
liposomes) allows drug release for prolonged considered from two perspectives, the
periods. Further by coating with or attaching particle size distribution and the lipid
ligands to SLNs there is a increased scope of crystalline state. Particle size is a critical
drug targetting. safety factor for parenteral administration
•• High drug payload.
and self life, as noted previously. Particle
•• SLN formulation stable for even the years
size greatly affects biodistribution and
have been developed. This is of paramount
importance with respect to the other colloidal RES clearance mechanisms. Particle size
carrier system . also affects the physical appearance of
•• SLNs particularly those in the range of the product, since the human eye can
120-200nm are not taken up readily by the cells only detect light scattered by particles
of the RES (Reticulo endothelial system) and that are greater than ~ 1. The degree of
thus bypass liver and spleen filtration. polydispersity can impact particle size
•• Excellent reproducibility with a cost effective
growth via Ostwald ripening and can
high pressure homogenization method as the
preparation procedure .
impact the overall drug release kinetics.
•• The feasibility of incorporating both hydrophilic The lipid crystalline state strongly
and hydrophobic drugs correlates with drug incorporation, drug
•• The solid matrix can (but need not) protect release, and the particle geometry
incorporated active ingredients/ drugs against
chemical degradation. The carrier lipids are
biodegradable and hence safe

9. Conclusion :
Lipid nanoparticle drug delivery technology presents significant opportunities for improving
medical therapeutics, but the technology’s potential remains unrealized. Several technology
challenges remain unsolved: appropriate control of particle size and size distribution, short-term
and long-term lipid crystallinity, drug loading profile, drug release kinetics, and greater control
of biodistribution once. SLNs delivery can be an innovative way to administer molecules into the
target site in a controlled manner by possibly overcoming or alleviating the solubility,
permeability and toxicity problems associated with the respective drug molecules. High physical
stability of these systems is another advantage. On the other hand the use of solid lipids as
matrix material for drug delivery is well known from lipid pellets for oral drug delivery . So
SLNs is a new era technology which has been taken over by the pharmaceutical industry. The
possibility of incorporating both the lipophillic and hydrophilic molecules and the possibility of
the several administration make the SLNs delivery system all the more promising. SLNs will
open a new channel for an effective delivery of a vast variety of drug molecules including
analgesics, antitubercular, anticancerous, antiaging, antianxiety, antibiotics, and antiviral
agents to the target site.

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