COLLEGE PROJECT REPORT

1. Solid Lipid
Nanoparticles
A PRESENTATION MADE UNDER THE
MODULE- PRACTICE SCHOOL
(B.PHARM 7TH SEMESTER)
PRIYANSHA SINGH (B.PHARM-
PANJAB UNIVERSITY, M.S. PHARM-
NIPER GUWAHATI)

2. ABSTRACT
During the recent years, attention is being focused on lipid based nano drug delivery system
to overcome some limitations of conventional formulations. Among these delivery systems
solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are promising
delivery systems due to the ease of manufacturing processes, scale up capability,
biocompatibility, and also biodegradability of formulation constituents and many other
advantages which could be related to specific route of administration or nature of the
materials are to be loaded to these delivery systems. The aim of this article is to review the
advantages and limitations of these delivery systems based on the route of administration
and to emphasis the effectiveness of such formulations.

3. INTRODUCTION
 WHAT ARE NANOPARTICLES?
Nanoparticle is a novel versatile drug delivery approach having targeted and drug site specific action.
Many of the recent formulation approaches utilize Nanotechnology for the preparation of Nanosized
structures containing the API. Nanoparticle is a nanosized colloidal particle with the size range of 1
to 1000 nm. In nano-particulate system, nano-suspensions are colloidal dispersions of nano-sized
drug particle that are produced by suitable method and stabilized by suitable stabilizer. Nanoparticles
are broadly divide into two categories (Nano-spheres and Nano-capsules), first is Nano-spheres are
solid core spherical particulates, which contain drug embedded within the matrix or adsorbed onto
the surface. (Matrix type). Second is Nano-capsules are vesicular system in which drug is essentially
encapsulated within the central core surrounded by a polymeric sheath. (Reservoir type). They show
improved efficacy, reduced toxicity, enhanced distribution and improved patient compliance

4.  TYPES OF NANOPARTICLES
Nanoparticle is a nano sized particle is mainly divided by thirteen types, Polymeric
Nanoparticles, Solid Lipid Nanoparticles, Nanosuspension, Polymeric Micelles,
Ceramic Nanoparticles, Liposome, Dendrimers, Magnetic Nanoparticles, Nanoshells
Coated With Gold, Nanowires, Nanopores, Quantum Dots, Ferrofluids

5. APPLICATIONS OF NANOTECHNOLOGY IN
PHARMACEUTICAL SCIENCES

6. SOLID LIPID NANOPARTICLES
 Now after a brief introduction of nanoparticles let us discuss about the most important example of
nanoparticles i.e. – solid lipid nanoparticles
(i) The solid lipid nanoparticles (SLN) are submicron colloidal carriers of size range between 3-300nm, which
are composed of physiological lipid, dispersed in water or in an aqueous surfactant solution. No potential
toxicity problems as organic solvents are not used. SLN are new generation of submicron sized lipid
emulsion where the liquid lipid (oil) has been substituted by a solid lipid so as to overcome the limitations
caused due to liquid state of oil droplets.
(ii) They consist of rigid hydrophobic center and phospholipid (acts as a surfactant) mono-layer coating. The
solid core consisting of a substance dissolved or dispersed in the high fat layer of the metal melting.
Phospholipids hydrophobic chains are found within the fat matrix. Drugs used are of BCS Class II and IV
(iii) They consist of macromolecular materials in which the active principle is dissolved, entrapped, and or to
which the active principle is adsorbed or attached.

7. Structure of a solid lipid nanoparticles
(Ref.-www.researchgate.net/figure/Structure-of-solid-lipid-nanoparticle-SLN_fig1_329144276, https://pubs.rsc.org/en/content/articlehtml/2020/ra/d0ra03491f)

8. EMERGENCE OF SOLID LIPID NANOPARTICLES
AS A NOVEL DRUG DELIVERY SYSTEM
The reasons for the increasing interest in lipid based system are:
(i) Lipids enhance oral bioavailability and reduce plasma profile variability.
(ii) An improved ability to address the key issues of technology transfer and manufacture scale-up.
(iii) Better control over drug release kinetics
(iv) Much easier to manufacture than bio polymer NPs
(v) Wider range of base materials (lipids)
(vi) Very high long-term stability
(vii) Chemical protection of labile incorporated compounds
(viii) No special solvents required
(ix) Application versatility

9. WHY S.L.N.’s ARE A BETTER DRUG
DELIVERY SYSTEMS THAN LIQUID
NANOEMULSION
(Ref. -https://www.slideshare.net/NIVETASINGH/solid-lipid-nanoparticles-74709943)

10. ADVANTAGES OF SOLID LIPID NANOPARTICLES

11. APPLICATIONS OF SOLID LIPID
NANOPARTICLES
 (i) SLN as potential new adjuvant for vaccines- Adjuvants are used in vaccination to enhance the immune response whereas the safer new
subunit vaccines are less effective in immunization and therefore effective adjuvants are required. New developments in this area are the
emulsion systems. These are oil-in-water emulsions that degrade rapidly in the body. Being in the solid state, the lipid components of SLNs
will be degraded more slowly providing a longer lasting exposure to the immune system.
 (ii) Solid lipid nanoparticles in cancer chemotherapy- due to improved stability of cytotoxic compounds by SLN encapsulation, improved
pharmacokinetics and drug bio-distribution by SLN & significant anticancer activity of SLN-encapsulated cytotoxic drug.
a) SLN as targeted carrier for anticancer drug to solid tumor- Tamoxifen is an anticancer drug incorporated in SLN to prolong the release of
drug after IV administration in breast cancer. Tumor targeting has been achieved with SLN loaded with drugs like methotrexate and
camptothecin.
b) SLN in breast cancer and lymph node metastases- e.g. - Mitoxantrone SLN local injections
 (iii) Solid lipid nanoparticles for delivering peptides and proteins- Formulation of proteins and peptides in SLN confers improved protein
stability, avoids proteolytic degradation, as well as sustained release of the incorporated molecules. For e.g. cyclosporine-A, insulin,
calcitonin and somatostatin have been incorporated into solid lipid particles and are currently under investigation.
 (iv) Solid lipid nanoparticles for targeted brain drug delivery as SLNs taken up readily by the brain due to their lipophilic nature. They have
high potential to treat brain cancer. Moreover new formulations of neuro-active drugs into SLN are expected to improve their
pharmacokinetic profile.

12.  (v) Solid lipid nanoparticles for parasitic diseases- SLN, due to their particulate nature and inherent structure exhibit good potential in the
treatment of parasitic infections.
 (vi) Solid lipid nanoparticles for ultrasonic drug and gene delivery- Solid lipid nanoparticles are used with ultrasound to deliver genes in vitro
and in vivo. The small packaging allows nanoparticles to extravasate into tumor tissues. Ultrasonic drug and gene delivery from nano-carriers
has tremendous potential because of the wide variety of drugs and genes that could be delivered to targeted tissues by fairly non-invasive
means.
 (vii) SLN applied to the treatment of malaria- The main drawbacks of conventional malaria chemotherapy are the development of multiple
drug resistance and the nonspecific targeting to intracellular parasites, resulting in high dose requirements and subsequent intolerable toxicity.
Here SLN’s have been receiving special attention with the aim of minimizing the side effects of drug therapy, such as poor bioavailability and
the selectivity of drugs.
 (viii) Targeted delivery of solid lipid nanoparticles for the treatment of lung diseases-Targeted delivery of drug molecules to organs or special
sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes,
micelles and nanoparticles a new frontier was opened for improving drug delivery. SLN’s with their special characteristics such as small
particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other
delivery systems
 (ix) SLN in cosmetic and dermatological preparations- applied in the preparation of sunscreens. SLN has UV reflecting properties.
 (x)Oral SLN in anti-tubercular therapy- Anti-tubercular drugs such as rifampicin, isoniazid, loaded SLNs able to decrease dosing frequency.

13. ROUTES OF ADMINISTRATION
 Routes of administration: Interactions of the SLN with the biological surroundings including:
distribution processes (adsorption of biological material on the particle surface and desorption of SLN
components into to biological surroundings) and enzymatic processes. Various administration routes
are
(i) Parenteral administration: Parenteral application of SLN reduces the possible side effects of drug
incorporated with the increased bioavailability.
(ii) Oral administration: Controlled release behavior of SLNs is reported to enable the bypass of gastric
and intestinal degradation of the encapsulated drug, and their possible uptake and transport through
the intestinal mucosa. However, the assessment of the stability of colloidal carriers in GI fluids is
essential in order to predict their suitability for oral administration.
(iii) Rectal administration: When rapid pharmacological effect is required, in some cases, rectal
administration is preferred. This route is used for pediatric patients due to easy application.

14. (i) Nasal administration: Nasal route is preferred due to its fast absorption and rapid
onset of drug action also avoiding degradation of labile drugs in the GIT and
insufficient transport across epithelial cell layers.
(ii) Respiratory delivery: Nebulization of solid lipid particles carrying anti-tubercular
drugs, anti-asthmatic drugs and anti-cancer was observed to be successful in
improving drug bioavailability and reducing the dosing frequency for better
management of pulmonary action.
(iii) Ocular administration: Biocompatibility and muco-adhesive properties of SLN
improve their interaction with ocular mucosa and prolong corneal residence time of
the drug, with the aim of ocular drug targeting.
(iv) Topical administration: SLN are very attractive colloidal carrier systems for skin
applications due to their various desirable effects on skin besides the characteristics of
a colloidal carrier system. They are well suited for use on damaged or inflamed skin
because they are based on non-irritant and non-toxic lipids.

15. A few examples showing the routes of administration of
SLN’s

16. TYPES OF SOLID LIPID
NANOPARTICLES
Solid lipid Nanoparticles can be divided into 3 types on the basis of drug loading:
 SLN Type I (Homogeneous matrix model/ solid solution)
 SLN Type II (Drug-enriched shell model)
 SLN Type III (Drug-enriched core model)
(https://www.slideshare.net/NIVETASINGH/solid-lipid-nanoparticles-7470994)

17. METHODS OF PREPARATION OF
SOLID LIPID NANOPARTICLES
a) GENERAL REQUIREMENTS-General ingredients include solid lipid, emulsifier
& water.
(i) Lipid contains triglycerides, partial glycerides, fatty acids, steroids, waxes
(ii) Combination of emulsifier might prevent particle agglomeration
(iii) Emulsifier include soybean lecithin, egg lecithin, poloxamer etc.

18. a) INFLUENCE OF FORMULATION VARIABLES USED ON PRODUCT QUALITY:-
(i) Influence of the lipid- due to increase in melting points of lipids and higher viscosity of dispersed
phase, the particle size of the SLN dispersion increases especially in the formulation of SLN’s from
hot homogenization method. There are variations seen in lipids in terms of their composition, the
suppliers and batch variation (e.g. by changing the zeta potential, retarding crystallization processes
etc.) Increasing the lipid content over 5%-3% result in larger particles and broader particle size
distribution in most cases.
(ii) Influence of emulsifier- Reduction in surface tension and particle partitioning during homogenization
is facilitated by increasing the emulsifier concentration. During SLN preparation the primary
dispersion must contain excessive emulsifier to rapidly cover the new surfaces formed during High
Pressure Homogenization; otherwise it will lead to agglomeration of uncovered new lipid surfaces.
The time taken for redistribution of emulsifier between new particle surfaces and micelles is different
for different types of surfactants. It has been studied that Low Molecular Weight surfactants will take
less time for redistribution and High Molecular Weight will take longer time for redistribution. The
addition of some co-emulsifying agent further decreases the particle size.

19. (iii) Influence of particle size- Alteration of the size significantly affects the physical stability, bio-
fate of the lipid particles, and release rate of the loaded drug. Hence the size of the SLNs has to
be controlled within reasonable range. Well formulated systems (liposomes, nano-spheres and
nanoparticles) should display a narrow particle size distribution in the submicron size range (as
having size below 1μm), according to the definition of colloidal particles.
(iv) Influence of the ingredients on product quality-The particle size of lipid nanoparticles is
affected by various parameters such as composition of the formulation (such as surfactant/
surfactant mixture, properties of the lipid and the drug incorporated), production methods and
conditions (such as time, temperature, pressure, cycle number, equipment, sterilization and
lyophilization). Large particle size is obtained at lower processing temperature like in hot
homogenization technique gives a smaller particle size, generally below 500 nm, and a narrow
particle size distribution as compared to cold homogenization. Mean particle size as well as
poly-dispersity index (PI) values are reported to be reduced at increasing homogenization
pressure up to 1500 bar and number of cycles (3-7 cycles).

20. METHODS OF PREPARATION
HIGH PRESSURE HOMOGENIZATION
It is a primary method which is powerful and the most reliable technique. High pressure homogenizers
push a liquid with high pressure through a narrow gap (in the range of a few microns). The fluid
accelerates on a very short distance to very high velocity. Very high shear stress disrupt the particles
down to the submicron range. Generally 5-3% lipid content is used but in a few cases lipid content up-to
40% has also been observed. HPH is of two types-hot homogenization and cold homogenization. In both
cases, a general preparatory step involves the drug incorporation into the bulk lipid by dissolving or
dispersing the drug in the lipid melt which is then subjected to a high speed homogenization to first
reduce the particles size, then subsequent finally the formation of solid lipid nanoparticles. However, the
subsequent steps differ.

21. Types of High Pressure Homogenization
Fig. 4 Hot Homogenization method Fig.5 Cold Homogenization method
(Ref. - https://www.researchgate.net/figure/Solid-lipid-nanoparticles-preparation-by-hot-homogenization-process_fig5_286981051 & https://www.researchgate.net/figure/Solid-lipid-nanoparticles-
preparation-by-cold-homogenization-process_fig7_266890262)

22. 1. Hot Homogenization method-The quality of the final product is affected by the quality of pre-emulsion to a large extent and it is desirable
to obtain droplets in the size range of a few micrometers. In general, higher temperatures result in lower particle sizes due to the decreased
viscosity of the inner phase. However, high temperatures also accelerate the degradation rate of the drug and the carrier. The
homogenization step can be repeated several times. It should always be kept in mind, that high pressure homogenization increases the
temperature of the sample (approximately 3°C for 500 bar). In most cases, 3–homogenization cycles at 500–1500 bar are sufficient.
Increasing the homogenization pressure or the number of cycles often results in an increase of the particle size due to particle coalescence
which occurs as a result high kinetic energy of the particles. The primary product is a nano-emulsion due to the liquid state of the lipid
which on cooling at room temperature leads to solid particles. Due to the small particle size and the presence of emulsifiers, lipid
crystallization may be highly retarded and the sample may remain as a super cooled melt for several months. The particle size so produced
by this method is <500nm.
2. Cold Homogenization method- Effective temperature control and regulation is needed in order to ensure the un-molten state of the lipid due
to increase in temperature during homogenization. Cold homogenization has been developed to overcome the following three problems of
the hot homogenization technique.
 1. Temperature-induced drug degradation able equipment.
 2. Drug distribution into the aqueous phase during homogenization
 3. Complexity of the crystallization step of the nano-emulsion leading to several modifications and/or super cooled melts pressure.
 In general, particle compared to hot homogenization, larger particle sizes and a broader particle size distribution.

23. Ultra Sonication Method
 In this probe sonicator or bath sonicator is use. By this method, nanoparticles of
size upto 80-800nm are formulated.
Fig. 6 Ultra-sonication method
Fig. - https://www.researchgate.net/figure/Fig-4-Schematic-representation-of-Ultrasonication-technique-and-or-high-
speed_fig2_287108838

24. Solvent evaporation method
 Upon evaporation of the solvent, nanoparticles dispersion is formed by
precipitation of the lipid in the aqueous medium by giving the nanoparticles of 25
nm
Fig. 7- Solvent evaporation method
(Ref. - https://www.slideshare.net/pankajwagh9/solid-lipid-nanoparticle)

25. SOLVENT EMULSIFICATION
DIFFUSION METHOD
 The particles with average diameters of 30-100 nm can be obtained by this
technique. Voidance of heat during the preparation is the most important advantage
of this technique.
 Advantage: Avoidance of any thermal stress
 Disadvantage: Use of organic solvents.
Fig. 8- Solvent emulsification diffusion method
(Ref. - https://www.slideshare.net/gajananingole39/solid-lipid-nanopaticle-as-promising-drug)

26. MICROEMULSION BASED METHOD
Fig. 9- Micro-emulsion based method
Ref. -https://www.researchgate.net/figure/Microemulsion-method-Advantages-1-Low-mechanical-energy-input-2-Theoretical-stability_fig3_261110084)
Preparation by stirring optically transparent mixture at 65-700C composed of a low melting fatty acid, emulsifier,
Co-emulsifier & water. This hot micro-emulsion dispersed in cold water (2-3oc) & stirring.

27. SUPERCRITICAL FLUID METHOD
It has an advantage of solvent-less processing. There are several variations in this platform technology for
powder and nanoparticle preparation. SLN can be prepared by the rapid expansion of supercritical carbon
dioxide solutions (RESS) method. Carbon dioxide (99.99%) was the good choice as a solvent for this
method.
Fig. 10- Supercritical fluid method
(Ref. - https://innovareacademics.in/journals/index.php/ijap/article/view/35312/21407)

28. SPRAY DRYING
It is an alternative and cheaper technique to the lyophilization process. This recommends the use of lipid with
melting point more than 700C. The best results were obtained with SLN concentration of 1% in a solution of
trehalose in water or 20% trehalose in ethanol-water mixture. The addition of carbohydrates and low lipid content
favor the preservation of the colloidal particle size in spray drying. The melting of the lipid can be minimized by
using ethanol–water mixtures instead of pure water due to cooling leads to small and heterogeneous crystals, the
lower inlet temperatures
Fig. 11- Spray drying method
(Ref. https://innovareacademics.in/journals/index.php/ijap/article/view/35312/21407)

29. PRECIPITATION METHOD
Fig. 12- Precipitation method
(Ref. - https://www.sciencedirect.com/science/article/abs/pii/S2352554117300347)

30. MISCALLANEOUS METHODS
FILM ULTRASOUND DISPERSION- The lipid and the drug were put into suitable organic solutions, after
decompression, rotation and evaporation of the organic solutions, a lipid film is formed, then the aqueous
solution which includes the emulsions was added. Using the ultrasound with the probe to diffuser at last, the
SLN with the little and uniform particle size is formed.
DOUBLE EMULSION METHOD- Here the drug is encapsulated with a stabilizer to prevent the partitioning
of drug in to external water phase during solvent evaporation in the external water phase of w/o/w double
emulsion.

31. PARTICLE SIZE ANALYSIS OF SOLID LIPID
NANOPARTICLES
(I) Photon correlation spectroscopy (PCS) and laser diffraction (LD) are the most powerful techniques for routine measurements of
particle size. PCS (also known as dynamic light scattering) measures the fluctuation of the intensity of the scattered light which is
caused by particle movement. This method covers a size range from a few nanometers to about 3 microns. PCS is a good tool to
characterize nanoparticles, but it is not able to detect larger micro particles. Electron Microscopy provides, in contrast to PCS and LD,
direct information on the particle shape.
(II) Photon Correlation Spectroscopy (PCS) - It is an established method which is based on dynamic scattering of laser light due to
Brownian motion of particles in solution/suspension. This method is suitable for the measurement of particles in the range of 3 nm to 3
mm. The PCS device consists of laser source, a sample cell (temperature controlled) and a detector. Photomultiplier is used as detector
to detect the scattered light. The PCS diameter is based on the intensity of the light scattering from the particles.
(III) Dynamic light scattering (DLS) - DLS also known as PCS records the variation in the intensity of the scattered light on the
microsecond time scale.
(IV) Static light scattering (SLS)/Fraunhofer diffraction- SLS is an ensemble method in which the light scattered from a solution of
particles is collected and fit into fundamental primary variable.

32. PARTICLE SIZE ANALYSIS OF SLN’s contd……
(I) Atomic force microscopy (AFM) - A probe tip with atomic scale sharpness is rastered across a sample to produce a
topological map based on forces at play between the tip and the surface.
(II) Acoustic methods- It measures the attenuation of the scattered sound waves as a means of determining size through the
fitting of physically relevant equations.
(III) Nuclear magnetic resonance (NMR) - NMR can be used to determine both the size and qualitative nature of nanoparticles.
(IV) Electron microscopy- Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) are the direct
method to measure nanoparticles, physical characterization of nanoparticles with the former method being used for
morphological examination. TEM has a smaller size limit of detection.

33. PARTICLE SIZE ANALYSIS OF SLN’s
contd….

34. CHARACTERIZATION OF SOLID LIPID
NANOPARTICLES
Characterization is a critical step in the formulation of SLNs dispersion which gives complete analytical detail of stability,
loading capacity, and release kinetics, polymorphism and particle size. Crystal behavior of lipid affects the drug loading, release
kinetics and stability of system. Highly crystalline system has less drug loading and slow release, so more stability in the
system.
A) MEASUREMENT OF ZETA POTENTIAL- The physical stability of optimized SLN dispersed is generally more than 12
months. ZP measurements allow predictions about the storage stability of colloidal dispersion. Polydispersity is basically
the ratio of standard deviation to the mean particle size.
B) DRUG CONTENT DETERMINATION- 1ml of the formulation is diluted with 5ml 0.5% Surfactant solution and made to undergo sonication
in a bath sonicator. Thereafter, the preparation is subjected to centrifugation at 12,000 rpm for 30 minutes at 4 °C. The supernatant is
collected and absorbance is measured at the corresponding lambda max 430nm.

35. DRUG CONTENT DETERMINATION contd…..
i. The entrapment efficiency for the SLN was studied by taking 1ml of the formulation and subjected to
centrifugation at 2000 rpm for 5 minutes. The supernatant was collected and the settled particles were washed
with Polar Solvent. Again, the centrifuges and the supernatant were added together and the absorbance was
measured at the Corresponding lambda max of in nm in particular drug by using ultraviolet-visible
spectrophotometer.
ii. Formula for calculating entrapment efficiency={{Drug concentration per ml of SLN x total volume of
dispersion}/ {total drug incorporated}}*30.
C) MEASUREMENT OF DEGREE OF CRYSTALLINITY- The geometric scattering of radiation from crystal planes within a solid
allow the presence or absence of the former to be determined thus the degree of crystallinity to be assessed. DSC can be used to
determine the nature and the speciation of crystallinity within nanoparticles through the measurement of glass and melting point
temperature. The geometric scattering of radiation from crystal planes within a solid allow the presence or absence of the former to
be determined thus the degree of crystallinity to be assessed. DSC can be used to determine the nature and the speciation of
crystallinity within nanoparticles through the measurement of glass and melting point temperature. The degree of crystallinity can
also be measured with the help of X-ray scattering & infrared spectroscopy.

36. D) In vitro RELEASE- In vitro release was evaluated using a dialysis bag diffusion technique. Drug loaded solid lipid nanoparticles (2 mg) were placed in dialysis
bags. The dialysis bag was tied at both ends. The dialysis bag was then placed 30 ml phosphate buffer solution (pH 7.4) at 37±1 ºC and under 30 rpm stirring.
Samples (5 ml) were withdrawn at predetermined time interval and replaced with the same volume of fresh dialyzing medium and the withdrawn samples were
assayed for drug content by measuring absorbance against the blank using UV spectrophotometer.
E) STABILITY STUDIES- For both SLNs dispersion and lyophilized SLNs, are stored at refrigerated condition (2-8ºC) and at room temperature, 25 °C ± 2 °C
(ambient) for 1 month and assay were evaluated immediately after production of the SLN and during one month (after 7, 15and 30 days) of storage at different
temperature conditions. The final formulations were also examined visually for the evidence of caking and discoloration.
F) STORAGE STABILITY STUDIES- The physical properties of SLN’s during prolonged storage can be determined by monitoring changes in zeta potential, particle
size, drug content, appearance and viscosity as the function of time. External parameters such as temperature and light appear to be of primary importance for long
– term stability. The zeta potential should be in general, remain higher than -60mV for a dispersion to remain physically stable.
 4oC - Most favorable storage temperature.
 20oC - Long term storage did not result in drug loaded SLN aggregation or loss of drug.
 500C - A rapid growth of particle size was observed.

37. G) Co – EXISTANCE OF ADDITIONAL STRUCTURES- The magnetic resonance techniques, nuclear magnetic
resonance (NMR) and electron spin resonance (ESR) are powerful tools to investigate dynamic phenomena and the
nano-compartments in the colloidal lipid dispersions. Dilution of the original SLN dispersion with water might cause
the removal of the surfactant molecules from the particle surface and induce further changes such as crystallization
changes of the lipid modification. Therefore to measure these changes a few parameters like molecular weight &
surface element analysis are conducted
i. Molecular weight- gel chromatography, X-ray photoelectron spectroscopy
ii. Surface element analysis- electrophoresis & laser Doppler anemometry.

38. STERILIZATION OF SOLID LIPID
NANOPARTICLES
 For intravenous and ocular administration SLN must be sterile. The temperature
reach during sterilization by autoclaving presumably causes a hot o/w micro
emulsion to form in the autoclave, and probably alters the size of the hot
nanoparticles. On subsequent slow cooling, the SLN reformed, but some nano-
droplets may coalesce, producing larger SLN than the initial ones. SLN are
washed before sterilization, amounts of surfactants and co surfactants present the
hot systems are smaller, so that the nano-droplets may be not sufficiently
stabilized.

39. PRINCIPLES OF DRUG RELEASE FROM
SOLID LIPID NANOPARTICLES
 The general drug principles of drug release from lipid nanoparticles are as follows:
a) Crystallinity behavior of the lipid and high mobility of the drug lead to fast drug release.
Crystallization degree and mobility of drug are inversely proportional to each other.
b) Slow drug release can be achieved when drug is homogenously dispersed in the lipid matrix. It
depends on the type and the drug entrapment model of SLN
c) Higher surface area due to smaller particle size in the nanometer size range gives higher drug release

40. RESULTS & DISCUSSION
The melting point, crystalline behavior of the carrier lipid and polymorphic characterization is done by differential scanning calorimetric
analysis (DSC), X-ray photoelectron spectroscopy and IR spectroscopy. The size of solid lipid nanoparticles on an average is reported to
be of 20nm to a few microns which is due to the presence of surfactants in solid lipid nanoparticles causing the interfacial film to
condense and stabilize. On size analysis they show polydispersity which is basically the ratio of standard deviation to the mean particle
size. The size ranges of nanoparticles were analyzed by various microscopic techniques, elution, chromatographic & spectroscopic
techniques, NMR and Light scattering principles. The zeta potential indicates the degree of charge present on suspended nanoparticles in
dispersion, higher the value of zeta potential confers stability as the particles then resist aggregation. The stability tests were conducted by
storing the formulation at various temperatures and then analyzing them over a fixed time interval for any change in its physical
properties & composition. The in-vitro release studies were so conducted so as to report its release properties at physiologic pH and
temperature as and then further analyzing the release properties by UV spectroscopy. Increase in the concentration of surfactant added
increases the entrapment efficiency due to the increase in the solubility of the drug in the lipid on increasing the concentration of the
surfactant. Depending upon the type and composition (which further influences the HLB value of the surfactants) of surfactant so added it
may either increase or decrease the rate of in-vitro release. The lower the HLB value lower will be the rate of drug release. The rate of
release of drug from the lipid matrix depends upon the lattice of the lipid & its melting point. Lower the melting point & order in a crystal
lattice of a lipid more controlled will be the rate of release of drug. Higher the melting point of the lipid used, slower the lipid
crystallization from the hot homogenization method resulting in an increase in particle size of SLN. Higher the molecular weight of the
surfactant & lower the HLB of the surfactant used lower will be the particle size.

41. RECENT ADVANCES
SLNs inculcate the properties of liposomes and polymer based carriers, where
encapsulation of both lipid soluble and water soluble drugs are possible. Production of
SLN is inexpensive, and scale up is feasible. They possess high stability during their
shelf life, and a wide range of lipids tune up the release kinetics. SLNs have emerged
as efficient drug delivery systems and the future of lipid based drug delivery is largely
dependent on SLNs due to their various significant properties. Scientists have already
filed many patents related to SLNs and we can anticipate more patented SLN-based
delivery systems in the near future.

42. CONCLUSION
SLNs particles are in sub-micron size due to this, more effective surface area and good
bioavailability is possible. Recent studies on brain targeting, lungs targeting, ophthalmic
delivery provides significant cellular uptake of drugs with less cytotoxicity. Nanotechnology
enabled drug delivery is opening prospective future in pharmaceutics. The emergence of
nanotechnology is likely to have a significant impact on drug delivery sector, affecting just
about every route of administration from oral to injectable. Nanotechnology focuses on the
very small and it is uniquely suited to creating systems that can better deliver drugs to tiny
areas within the body. Nano-enabled drug delivery also makes it possible for drugs to
permeate through cell walls, which is of critical importance to the expected growth of genetic
medicine over the next few years.

43. REFERENCES
https://www.researchgate.net/publication/324562176_Current_status_of_Solid_Lipid_Nanoparticles_A_review
1. https://www.researchgate.net/publication/287716187_Solid_lipid_nanoparticles-_A_review
2. https://www.researchgate.net/publication/266229322_Solid_Lipid_Nanoparticles_A_Promising_Drug
_Delivery_Technology
3. https://www.researchgate.net/publication/283600259_Solid_lipid_nanoparticles_A_promising_drug_d
elivery_system
4. https://www.researchgate.net/publication/286981051_A_review_on_solid_lipid_nanoparticles
5. https://www.tsijournals.com/articles/solid-lipid-nanoparticles-a-review.pdf
6. https://www.researchgate.net/publication/309489670_SOLID_LIPID_NANOPARTICLES-
A_REVIEW
7. http://www.iosrphr.org/papers/v2i6/Part_1/F0263444.pdf

44. REFERENCES contd…..
1. http://www.jcreview.com/fulltext/197-1572428146.pdf
2. https://ijpsr.com/bft-article/solid-lipid-nanoparticles-an-effective-and-promising-drug-delivery-system-a-
review/?view=fulltext
3. file:///C:/Users/priyansha%20singh/Downloads/pharmaceutics-10-00191%20(4).pdf
4. https://www.researchgate.net/publication/336835326_Preparation_and_Characterization_of_Solid_Lipid_Nanoparticles
5. https://www.researchgate.net/publication/270116628_Solid_Lipid_Nanoparticles_SLN_Method_Characterization_and_Applic
ations-_Review
6. https://www.researchgate.net/publication/44630382_Solid_Lipid_Nanoparticles_A_Modern_Formulation_Approach_in_Drug
_Delivery_System
7. https://www.slideshare.net/sagarsavale1/solid-lipid-nanoparticle
8. https://www.slideshare.net/NIVETASINGH/solid-lipid-nanoparticles-74709943
9. https://www.slideshare.net/gajananingole39/solid-lipid-nanopaticle-as-promising-drug