Presentation on niosomes in pharma

2. Introduction
• Significant thought has been given in recent decades to the
development of innovative drug delivery systems (NDDS).
• It endures to meet two requirements. Rightfully, it should provide
the drug at a rate determined by the body's requirements specific to
the extent of therapy.
• Another justification is that it must deliver the majority to the
intended position. Different factors prevent traditional therapy with
delayed discharge dosage schemes from providing these
necessities
• There are many different types of medicinal carriers available,
including particulate, polymeric, macromolecular, and cell
components. A colloidal carrier framework is another name for a
particle type transporter, which can be microspheres,
pharmacosomes, lipid particles, virosomes, polymeric micelles,
liposomes, niosomes, nanoparticles, etc.

3. • Vesicles typically consist of a number of different amphiphilic building
elements.
1) Vesicular systems
2) Vesicular System – Niosomes
Niosomes:
• Niosomes are nano-sized vesicle that are created when artificial non-
ionic surfactants are absorbed by a media with or without cholesterol .
• The niosomal bilayer is generated by non-ionic surfactants, which is
how the two systems vary from liposomal systems. Even then,
phospholipids or lipids are used to produce the liposomal.
• The range of diameters is 10 to 1000 nm.
• Niosomes are thought to be superior than liposomes because the
surfactants are more chemically stable than phospholipids.

4. Structure of Niosomes
• Niosomes are tiny lamellar structures made when a number of vesicular
systems combine surfactants with ethers in the aqueous phase.
• . Surface-active compounds create micellar formations when more
water is added.
• Both unilamellar and multilamellar niosomes are possible.
Structure of niosomes

5. Salient features of niosomes
In a manner similar to liposomes, niosomes are in charge
of encasing solutes.
• Such vesicular entities were already active and osmotically stable.
• It is composed of an infrastructure that primarily combines
hydrophobic and hydrophilic components.
• Offers excellent structural stability (size, composition, and fluidity).
• The medication molecules performed better and stayed in the
bloodstream longer.
• It has been shown that limiting the integration of medicines to
untargeted locations increases bioavailability.
• Offers regulated medication delivery at a particular spot.

6. Factors Affecting Niosomal Preparation
1. Nature of surfactant
2. Structure of surfactant
3. Composition of membrane
4. Encapsulated medication nature
5. Hydration temperature
6. Weight of Cholesterol
7. Charge
8. Osmotic stress resistance

7. Techniques of preparation of niosomes
• Trans Membrane pH Gradient/Drug Uptake System
• Hydration to thin film system
• Microfludisation
• Injection ether system
• Proniosomes
• Hydration
• Evaporation by Reverse Phase
• Bubble System

8. Niosome formulation criteria
1. Surfactants nature
2. Inducer of charge
3. Bio-adhesive polymer
4. Steric barrier
5. Stabilizer

9. Applications
• Niosomes as Drug Carriers
• Diagnostic imaging with niosomes
• Ophthalmic drug delivery
• Targeting of bioactive agents
• RES
• Delivery of peptide drugs
• Anti-neoplastic treatment
• Daunorubicin
• Doxorubicin
• The Methotrexate
• The Bleomycin
• The Vincristine
• Noisome as a brain targeted vasoactive intestinal peptide (VIP)
delivery system

10. Profile of drug
• Naringin
Between the flavanone naringenin and the disaccharide
neohesperidose, naringin is a flavanone-7-O-glycoside. In citrus
fruits, the flavonoid naringin naturally exists. The aglycone part of
naringin, also known as naringenin, has one rhamnose and one
glucose unit connected to it in addition to the fundamental flavonoid
structure.
• Molecular formula: C27H32O14
• Molecular weight: 272.257 g/mol
• Melting point: 166° C
• Pka: 7.86
• Solubility: ethyl acetate
• Appearance: white powder
• Uses: Citrus-based products are frequently utilised for their anti-
inflammatory, anti-diabetic, anti-oxidant, and anti-tumor properties

11. Excipient Profile
Cholesterol (67-71)
The vertebrate body contains the animal sterol cholesterol, which is usually
found in larger concentrations in the liver, medulla spinalis, and brain. It is
a crucial membrane component that maintains stability, a precursor to the
synthesis of vitamin-D.
Span 80
Span 80 is an emulsifier of the water/oil type that is a light yellow
viscous oily liquid with the capacity to combine with emulsifiers S60
and T60 and has an HLB value of 4.3. It has been employed as a
softener, stabiliser, solubilizer, anti-static agent, and emulsifier in a
variety of formulations.

12. Experimental work
1. Pre-formulation
2. Organoleptic Characteristics:
3. Melting-Point
4. HPLC analysis of Naringin
Estimation of Naringin
Estimation of naringin by HPLC
a) Blank
b) Preparation of Standard stock-solution
c) Preparation of sample solution

13. Solubility Studies
• Solubility is the simultaneous interaction of two or more substances
to produce a regular chemical distribution.
• A huge number of medications are placed in carefully cleaned test
tubes with 1 ml of different solvents (Methanol, Ethanol, Acetone,
ethyl acetate, chloroform, 0.1N-HCl, water, PBS with pH 6.8 & 7.4)
for the research of quantitative solubility. Test tubes were then
firmly closed.
• These test tubes were shaken for 24 hours at 25°C temperature
using a water bath shaker. Each solution was filtered at 15,000 rpm
after 24 hours, and the supernatant was discarded. After filtering the
supernatant, the filtrates were suitably diluted and sent to HPLC
analysis to assess their composition.

14. Sr.no Solvent system Solubility of drug (mg/ml)
01. Water 0.082 ± 0.002
02. Buffer pH 7.4 1.518 ± 0.000
03. Chloroform 2.174 ± 0.011
04. Acetone 6.678 ± 0.0010
05. Methanol 9.628 ± 0.008
06. Ethanol 9.741 ± 0.006
07. DMF 14.08 ± 0.005
08. Ethyl acetate 14.330 ± 0.007

15. Partition Coefficient of Drug
• Partition coefficient (oil/water) can be used to assess a drug's lipophilicity
and hydrophilicity as well as its ability to cross cell walls. It is sometimes
referred to as the unionised product's contribution to the equilibrium
between the organic and aqueous phases.
• Po/w = The partition coefficient (Po/w) is consequently the ratio of
the simultaneous drug concentrations in n-octanol and water, and it
is commonly expressed as its logarithm to base 10 (log P).
Shake flask system
In 10 ml of n-octanol and water (1:1), excess Naringin was
dissolved, and the mixture was then permitted to sit for twenty-four
hours. After 24 hours, the two layers were separated and centrifuged
at 15,000 rpm for 15 minutes. The AOC was collected in HPLC at
the proper maximum concentration following the correct dilution

16. Partition
coefficient of
drug
Solvent system Log P value Refernces
Naringin
n-octanol: water
6.207 ± 0.003 6.34
Naringin's partition coefficient in n-octanol:water was discovered to be
6.343 0.003, which is consistent with the literature and suggests that
the medication is lipophilic in nature

17. FTIR of Naringin and Excipients
• For structural investigation, FTIR spectroscopy was employed.
• The technology of salt (KBr) discs was used.
• Only the spectrum of the sample is obtained since the KBr exhibits no
absorption in the basic area of the IR spectrum.
• For the purpose of determining how well the drug interacts with the
excipients, an FT-IR spectra of naringin and the drug + excipient
combination was recorded .
• 100 mg of spectroscopic grade KBr that had been dried using an IR light
and 1 mg of naringin/excipients in addition to the medicine were used to
make the KBr disc.
• Naringin and KBr were combined, then disc was created under hydraulic
pressure. The FT-IR chamber was used with this disc. spectrum was
captured between 4000 and 400 cm-1.

18. • Picture
The principal infrared absorption peaks of naringin were found at 3343.07
cm-1 (O - H stretching), 1687.01 cm-1 (symmetrical stretching of the
functional group C = O), 976.16 cm-1 (planar deformation of dual bond C
= C - H), 855.24 cm-1 (planar deformation of dual bond C = C - C), and
608.03 cm-1 (planar deformation of dual bond C = C - O). Such observed
major peaks attested to the purity and validity of naringin

19. UV-visible
Calibration curve of Naringin using methanol as a solvent (λmax = 280nm)

20. Preparations of Niosomes of naringin
• Niosomes were created with the thin film hydration systemology.
• The non-ionic surfactant and cholesterol were dispersed in the solvent
combination of methanol and chloroform (1:2v/v) with the addition of
naringin, which was weighed as a dosage, at various specified molar ratios
(1:1, 2:1, and 3:1; surfactant: cholesterol M.R).
• The mixture was transferred to a 100-mL flask, and the solvent was
evaporated under reduced pressure at 60 ° C.
• The solvent combination was evaporated completely until there was
just a thin film left on the flask. Vacuuming was done overnight to get
rid of extra solvent. The lipid film was hydrated using pH 7.4
phosphate buffer in 10 mL.

21. • The mixture was circulated within the rotary evaporator at 60 ° C for an
hour while hydration continued. After being suspended for two hours to fully
inflate them, they were sonicated for around ten minutes, and the size
analysis was carried out right away.
• picture

22. Evaluation of Naringin Niosomes
1) Optical microscopy
The vesicle's structure was confirmed using optical microscopy
with a 45-nanometer resolution. The production of vesicles was
seen in niosomal solutions that were spread out across glass
plates and dried at temperatures by dry air. Niosomes A
microscope's lens is frequently used for microphotography.
picture

23. Surface morphology, size of particle and
Zeta potential
 Transmission electron microscopy (TEM) was used to determine the niosome
morphological analysis.
 Niosomal sol was placed in small amounts (10 L) on a grid and forced to face
for two minutes. Next, a little piece of filter paper was taken out of the
additional niosomal solution.
 The carbon grid has been stained with a reduction of the -ve stain-solution, (2%
w/v) acetic-Uranium solution.
 After two minutes, the additional staining compound has been removed by
adsorbing a drop on the filter paper and letting the sample air dry.
 A transmission microscope was used to display the thin film of the darkened
vesicles at a voltage of 70 kV (101).
 The particle size was determined using dynamic light scattering (DLS)
technology from Agilent Technologies in the USA.

24. picture

25. Entrapment Efficiency
• Dialysis was used to quantify the amount of naringin that was confined inside
the niosomes after the unenclosed substance was removed.
• Niosomal dispersion from a dialysis bag that had been submerged in a beaker
filled with 100 ml of PBS with a pH of seven was used to measure the
effectiveness of the dialysis process.
• The beaker has been rotating at a speed of 120 rpm for 4 hours.
• Then, using HPLC, the reaction inside the receptor compartment was examined
for uncontrolled naringin.
• The ratio of the difference between the total amount of the drug added and the
amount of unentrapped drug has been used to determine the PDE and inside
niosomes

26. • picture

27. An examination of Niosomal Gel
• Physical-appearance
• The PH
• Melting point
• pH
• Drug content

28. In-Vitro testing of Drug Release
The kinetics of drug release
1) First order
2) Zero order
3) higuchi model
4) Korsmeyer Peppas

29. The kinetics of zero order
Simple definitions of a zero command release include:
Q0-K0 t = Qt Where,
Qt = Amount of drug dissolved in time t.
Q0 = Initial amount of drug inside the solution (most of the time, Q0 = 0)
K0 = Constant of zero-order release expressed in concentration / time units

30. Kinetics to the first order
The equation also describes how the product discharges after first order
kinetics:
LogC = C0log- Where,
C0 = Drug 's initial concentration
K = Constant rate of first order
T = Time.

31. Higuchi model
The streamlined Higuchi equation is shown below;
Qt = 0.5 kH(t) where,
Qt =Amount of drug released in time t
KH = Constant release rate

32. Korsmeyer-Peppas Model
The rate of discharge of regulated polymer release matrices is often defined in
Korsmeyer et al 's proposed equation
Q = To K.tn Where,
Q = Percentage of drug released at the moment
K = kinetic constant
N = Diffusional exponent of the release mechanism

33. Summary & conclusion
• The colloidal drug delivery method should ideally fulfil two prerequisites.
• First off, it will provide the drug over the course of the therapy at a rate dictated by
the body's requirements.
• The active agent will be directed to the surgery site.
• After a physicochemical analysis, it was discovered that Naringin has a melting
point of 166°C. According to an HPLC investigation, the maximum absorption in
methanol is 285 nm.
• In methanol, ethanol, ethyl acetate, dimethyl formamide, dimethyl sulfoxide, and
acetone, the drug was less soluble and easily soluble in chloroform and water.
• It was discovered that the naringin partition coefficient in n-octanol: water was
6.207 0.003, which shows the chemical is lipophilic.

34. • The preparation of Naringin niosomal gel is being attempted utilising a variety
of surfactant grades, including Span 60 and Span 80.
• In which case it was discovered that Span 80 facilitated niosome formation.
• The prepared niosomes' particle size was determined to be The region from-
28.8 mV was where the percentage effectiveness of trapping was discovered.
• The ratio with the best trap effectiveness and ideal shape was chosen to prepare
Carbopol 934P niosomal gel in various concentrations.
• Niosomal gel was produced at a pH of 7.24 0.024% and 7.35 0.01, respectively.
• A percentage of the drug content was found in all formulations with gel
formation, ranging from 77.200.064 to 88.830.05.
• Data from in vitro experiments indicated that 93% of the pure medication was
released within 6 hours. The drug release from the Formulation F8-prepared
niosomal gel exceeded 72.950.271 percent after 24 hours.

35. • According to systems for model fitting, the Korsmeyer Peppas order model
has a highest regression coefficient (R2) value of 0.919.
• By carefully planning the formulation and selecting an efficient preparation
method, we came to the conclusion that the medicine Naringin can be
released with a sustained release.
• The procedure utilised to make niosomal gel has been proven to be
straightforward, repeatable, having acceptable morphology, and being
effective in trapping.
• The developed compound showed greater sustained release behaviour when
compared to its pure naringin counterpart. Consequently, span 80 might be
viewed as a crucial carrier for creating a system for transdermal medication
administration.

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