RATHNA MP.pptx

MOLECULAR PHARMACEUTICS
MICROSPHERES,NIOSOMES,AQUASOMES,
PHYTOSOMESAND ELECTROSOMES
Presented
By
Rathnamoorthi V
M.Pharm-First Year
Department of Pharmaceutics
Nandha College of Pharmacy
Erode-52 1
7/2/2023
RATHNAMOORTHI.V-M.PHARM

CONTENTS
Introduction
Preparation
Evaluation and
 Application of the followings:
MICROSPHERES
NIOSOMES
 AQUASOMES
PHYTOSOMES
ELECTROSOMES 2
7/2/2023

MICROSPHERES / MICROCAPSULES
Microencapsulation of pharmaceuticals was first
investigated in the year 1931 by preparing spheres of
gelatin using coacervation technique.
The micro particulate delivery systems are considered and
accepted as a reliable means to deliver the drug to the
target site with specificity, if modified, and to maintain the
desired concentration at the site of interest without
untoward effect.
Microspheres are small spherical particles with diameters
from 1 to 1000 μm
Microspheres are also known as microparticles.
 Microspheres can be produced from several natural and
synthetic polymeric materials or even from inorganic
materials
3
7/2/2023

Microspheres
 Small spherical particles.
 Solid matrix particle.
 It is a micrometric reservoir system.
 Diameter ranges from 1µ to 1000µ
4
7/2/2023

Microcapsules
 Microcapsules can be the
small entities that contain
an active agent or core
material surrounded by a
shell or embedded into a
matrix structure
 It is a micrometric matrix
system
5
7/2/2023

ADVANTAGES
 Sustained or prolonged release of the drug.
Eg : Glibenclamide.
 To masking the organoleptic properties.
Eg: Paracetamol, Nitrofurantoine.
 Liquid drugs can be converted in a free flowing powder.
 The drugs sensitive to moisture, light and oxygen can be
protected by this technique.
Eg: Nifedipine-Photo instability.
 Prevent the incompatibility between drugs.
Eg: Hydroquinone.
6
7/2/2023

DISADVANTAGES
 The costs of the materials higher than those of standard
formulations.
 The fate of polymer matrix and its effect on the
environment.
 The fate of polymer additives such as plasticizers,
stabilizers, antioxidants and fillers.
 Reproducibility is less.
 Process conditions like change in temperature, pH, solvent
addition, and evaporation/agitation may influence the
stability of core particles to be encapsulated.
7
7/2/2023

IDEALCHARACTERISTICS
 Longer duration of action
 Increase of therapeutic efficiency
 Control of content release
 Protection of drugs
 Reduction of toxicity
 Biocompatibility
 Relative stability
 Water solubility or dispersability
 Bioresorbability
 Targetability
8
7/2/2023

POLYMERS:
SYNTHETIC POLYMERS
Non-biodegradable
 Acrolein
 Epoxy polymers
Biodegradable
 Polyanhydrides
 Polyalkylcyanoacrylates
 Lactides and glycolides
and their copolymers
NATURAL MATERIALS
Proteins
 Albumin, Gelatin,
Collagen
Carbohydrates
 Starch,Agarose,
 Chitosan
Chemically modified
Carbohydrates
 Poly(acryl)dextran
 Poly(acryl)starch.
9
EXAMPLES
PLGA Gelatin microspheres
Dextran microspheres
Polyanhydride microspheres
Chitosan microspheres
7/2/2023

Materials used for preparation
Core material
 The core material, defined as the specific material to be
coated, can be liquid or solid in nature.
 The solid core be active constituents, stabilizers, diluents,
excipients, and release-rate retardants or accelerators.
 Liquid Core Material- Solvents, catalyst, sugars, salts.
 Solid Core Material- Dextrins, minerals, bases,
pharmaceuticals.
Coating material
 Eg: Ethyl cellulose, carboxylate and amino derivatives.
Water Soluble resins
 Hydroxyethylcellulose, Polyvinylpyrrolidine,starch.
Water insoluble resins
 EthylCellulose,Polyethylene,Polymethacrylate
10
7/2/2023

METHODS OFPREPARATION:
1) Single Emulsion Technique
2) Double Emulsion Technique
3) Polymerization Technique
4) Phase Separation Coacervation
5) Spray drying
6) Solvent Extraction
11
7/2/2023

1) Single Emulsion Technique
Aqueous solution /suspension of polymer
Stirring / sonication
Dispersion in organic phase oil/chloroform
Cross linking
Heat denaturation Chemical cross linking
By adding dispersion to heated oil ( Glutaraldehyde,HCHO,
CHCl3 )
12
7/2/2023

Microspheres in organic phase
Centrifugation,washing,separation
Microspheres
13
7/2/2023

2) Double Emulsion Technique
Aqueous solution of polymer
Dispersion in oil/organic phase, vigorous
homogenization(sonication )
Primary emulsion(w/o)
Addition of aqueous solution of PVA
W/O/W multiple emulsion
Addition to large Aqueous phase
denaturation /hardening
Microspheres in solution
Separation, washing, Drying
Microspheres 14
7/2/2023

3)Polymerization technique
Types:
1. Bulk polymerization
2. Suspension precipitation polymerization
3. Emulsion polymerization
4. Miceller polymerization
15
7/2/2023

Bulk polymerization:
Monomer Bioactive material Initiator
Heated to initiate polymerization
Initiator accelerate rate of
Reaction
Polymer(Block)
Moulded/fragmented
MICROSPHERES
16
7/2/2023

Suspension polymerization
Monomer Bioactive material Initiator
Dispersion in water and stabilizer
Droplets
Polymerization Vigorous agitation
Heat/irradiation
Separation and Drying
MICROSPHERES
17
7/2/2023

Emulsion Polymerization
Monomer/ Aq.Solution of NaOH,
Bioactive material Initiator, Surfactant , Stabilizer
Dispersion with vigorous stirring
Micellar sol. of polymer in aqueous medium
Polymerization
Microspheres formation
MICROSPHERES
18
7/2/2023

4)Phase Separation Coacervation
Aq./organic solution of polymer
Drug
Drug dispersed or dissolved in the polymer solution
Phase separation by different means
Polymer rich in globules
Hardening
Microspheres in aq./organic phase
Separation / Drying
MICROSPHERES
19
7/2/2023

5)Spray Drying
Polymer dissolve in volatile organic solvent
(Acetone, Dichloromethane)
Drug dispersed in polymer solution under high speed
homogenization
Atomized in a stream of hot air
Small droplets or fine mist form
20
C
7/2/2023

Leads to formation of Microspheres due to solvent
evaporation
Microspheres separated from hot air by cyclone separator
Trace of solvent are removed by vacuum drying
21
7/2/2023

6)Solvent extraction
Drug is dispersed in organic solvent
Organic phase is removed by extraction with water
(This process decreasing hardening time for microspheres)
Hardened microspheres
22
7/2/2023

FACTORSAFFECTING RELEASE OFTHE DRUG
Drug
 Position in microspheres
 Molecular weight
 Physiochemical properties
 Concentration
 Interaction with matrix
Environment
 pH
 Polarity
 Presence of enzyme
23
7/2/2023

DETERMINATION OF SHAPE AND
STRUCTURE OF MICRO PARTICLES
 Light microscopy
 Laser light scattering microscopy
 Scanning electron microscopy
 Confocal laser scanning microscopy
Electron microscopy for chemical analysis
 Used to determine the atomic composition of the surface .
 FTIR - Degradation of polymer matrix of the system
 Attenuated Total Reflectance FTIR – It provides
information about surface composition of the microsphere.
24
7/2/2023

Application of microspheres in pharmaceutical
industry
 For taste and odour masking
 To delay the volatilization
 For separation of incompatible substances
 For improvement of flow properties of powders
 To increase the stability of the drug against the external
conditions
 For safe handling of toxic substances
 To improve the solubility of water insoluble
 Substances by incorporating dispersion of such in aqueous
media
 For targeting delivery of Anti-neoplastic drug.
 In vaccine delivery.
 In cosmetic industry.
25
7/2/2023

TARGETING USING MICRO PARTICULATE CARRIERS
 Targeting means “The therapeutic efficacy of the drug relies on its access
and specific interaction with its candidate receptors.”
Ocular
 The eye and the cornea are easily accessible targets.
 The retention of micro particulate system can be attained by using gel
form.
Nasal
 The intranasal route is exploited for the delivery of the peptides and
proteins.
 Bio adhesive microspheres are used as alternative to the gel dosage
formulations.
Oral
 The most preferred convenient route.
 It also preferred for delivery of soluble antigen.
26
7/2/2023

Magnetic microspheres
 It is a biophysical approach.
 Magnetic microspheres are prepared by mixing water
soluble drugs and 10 nm magnetite in aqueous solvent of
matrix material.
 Magnetic targeting is based on the force exerted by
external magnetic field over the magnetically susceptible
microspheres
 Eg: Amphotericin B ,Interleukin 2.
Microspheres in vaccine drug delivery
 Biodegradable delivery system of vaccine can be given by
parenteral route.
 Polymers used- Poly lactic acid, poly glycolic acid,
polylactides co glycosides.
 Eg: Diphtheria toxoid, Hepatitis B surface antigen.
27
7/2/2023

EVALUATION
• 1. Morphological examination
• 2. Production yield, drug content, and loading efficiency
Percentage of Production Yield = W1 / W2 × 100
• 3. Particle size measurement
• 4. Determination of bulk density and angle of repose
• 5. Zeta potential study
• 6.Adhesion study
• 7. Swelling property
• 8. Infrared absorption study
• 9. Isoelectric point determination
• 10. Chemical analysis
• 11. Surface carboxylic acid residue
28
7/2/2023

NIOSOMES
DEFINITION
• Niosome are non-ionic surfactant vesicles obtained on
hydration of synthetic nonionic surfactants with or without
incorporation of cholesterol or their lipids.
• They are structurally similar to liposomes in having a
bilayer
• However, the materials used to prepare niosomes make
them more stable and thus niosomes offer many more
advantages over liposomes.
• The sizes of niosomes are microscopic and lie in
nanometric scale.
• The particle size ranges from 10nm-100nm.
29
7/2/2023

STRUCTURE OFNIOSOME
30
7/2/2023

ADVANTAGES
1. The vesicle suspension being water based offers greater
Patient Compliance over oil based systems.
2. Since the structure of the Niosome offers place to
accommodate hydrophilic, lipophilic as well as
amphiphilic drug moieties, they can be used for a variety
of drugs.
3. The characteristics such as size, lamellarity etc. of the
vesicle can be varied depending on the requirement.
4. The vesicles can act as a Depot to release the drug slowly
and offer a controlled release.
5. Due to their ability to entrap both hydrophobic and
hydrophilic drugs, niosomes are reported as ideal carriers
for the delivery of drugs such as doxorubicin, vaccines,
insulin, siRNA and so on.
31
7/2/2023

DISADVANTAGES
• Physical instability
• Aggregation
• Fusion
• Leaking of entrapped drug
• Hydrolysis of encapsulated drugs which limiting the shelf
life of the dispersion.
COMPOSITIONS
• The major components used for the preparation of
Niosomes are,
1. Non-ionic surfactants
2. Cholesterol
3. Drug
4. Ionic amphiphiles
32
7/2/2023

CONTD…
1. Non ionic surfactant- are the main ingredient, rather
than phospholipid. Non-ionic surfactants used in the
niosomes are amphipathic, including terpenoids,
polysorbates, Spans, alkyl oxyethylenes etc.
2. Cholestrol- The proper amount of cholesterol is added to
the niosomes to achieve the most stable formulation due
to its interaction with non-ionic surfactants . It plays the
role of regulating the structure and flexibility of the
membrane as a dependable buffer.
3. Drug- Both hydrophilic and hydrophobic drugs, can be
encapsulated in the niosomes.
4. Ionic amphiphiles -used in the niosomes for three
purposes: loading drugs, increasing the efficacy and
enhancing stability 33
7/2/2023

PREPARATION METHODS OFNIOSOMES
A. Ether injection method
B. Hand shaking method (thin film hydration technique)
C. Sonication Method
D. Micro fluidization method
E. Multiple membrane extrusion method
F. Reverse phase evaporation technique (REV)
G. Trans membranes pH gradient (inside acidic) Drug upake
Process: or remote loading technique
A. Formation of Niosomes from Proniosomes
34
7/2/2023

A. ETHER INJECTION METHOD
Preparation steps:
Surfactant is dissolved in diethyl ether
↓
Then injected in warm water maintained at 60°C through a
14
gauze needle
↓
Ether is vaporized to form single layered Niosomes.
35
7/2/2023

36
7/2/2023

B. HAND SHAKING METHOD (THIN FILM
HYDRATION TECHNIQUE)
Preparation steps:
Surfactant + cholesterol + solvent
↓
Remove organic solvent at Room temperature
↓
Thin layer formed on the Walls of flask
↓
Film can be rehydrated to form multilamellar Niosomes.
37
7/2/2023

38
Hand shaking method
7/2/2023

C. SONICATION METHOD
Preparation steps
Drug in buffer + surfactant/cholesterol in 10 ml
↓
Above mixture is sonicated for 3 min at 60°C using titanium
probe yielding niosomes.
39
7/2/2023

D. MICRO FLUIDIZATION METHOD
• It is a new method for formulation of Niosome
• It is based on jet principle
• By mixing two kinds of fluids such as alcohol and water in
Microchannels
PREPARATION
Two kinds of fluid in ultra high speed jets inside
interaction chamber
↓
Impingement of thin layer of Liquid in micro
channels
↓
Formation of uniform Niosomes
.
40
7/2/2023

E. MULTIPLE MEMBRANE EXTRUSION
METHOD
• Mixture of surfactant, cholesterol and diethyl phosphate in
chloroform is made into thin film by evaporation.
• The film is hydrated with aqueous drug solution.
• Resultant suspension is extruded through polycarbonate
membranes which are placed in series upto 8 passages
41
7/2/2023

F. REVERSE PHASE EVAPORATION TECHNIQUE
(REV)
Cholesterol + surfactant dissolved in ether + chloroform
↓
Sonicated at 5°c and again Sonicated after adding PBS
↓
Drug in aqueous phase is added to above mixture
↓
Viscous Niosomes suspension is diluted with PBS
↓
Organic phase is removed at 40°C at low pressure
↓
Heated on a water bath for 60°C for 10 mins to yield
Niosomes.
42
7/2/2023

EVALUATION
• Drug Content
• Entrapment Efficiency
• Stability Study
• Invitro Drug Release
• Vesicle Diameter
• Optical Microscopy method
• Partition Coefficient
43
7/2/2023

AQUASOMES
DEFINITION
• Aquasomes are nanoparticulate carrier system but instead of
being simple nanoparticle these are three layered self
assembled structures.
• This three layered system contains a Core coated with
Polyhydroxy oligomer upon which Biochemically active
molecules are adsorbed.
• Ceramics are mainly used as core material because of high
degree of order and structural regularity.
• Polyhydroxy oligomer coating provides water like
environment & protect biochemically active molecule from
dehydration.
• Particle size lower than 1000 nm. 44
7/2/2023

METHOD OF PREPARATION OF AQUASOMES
3steps.
• I - Formation of an inorganic core
• II - Coating of the core with polyhydroxy oligomer
• III- Loading of the drug of choice to this assembly
45
7/2/2023

I. FORMATION OF AN INORGANIC CORE
Core preparation
• Preparation technique of core depends on the type of core to be
used.
• Generally nanocrystalline tin oxide, carbon ceramic
(diamond), calcium phosphate, hydroxyapatite are used as
core. Among these materials nanocrystalline calcium
phosphate and hydroxyapatite are widely used as core material
for aquasomes.
Types:
a) Synthesis of nanocrystalline tin oxide core ceramic
b) Self assembled nano crystalline brushite (calcium phosphate
dihydrate)
c) Nanocrystalline carbon ceramic, diamond particles 46
7/2/2023

II. COATING OF THE CORE WITH POLYHYDROXY
OLIGOMER
• In the second step, ceramic cores are coated with carbohydrate
(Polyhydroxyl Oligomer).
• The coating is carried out by addition of carbohydrate into an
aqueous dispersion of the core under Sonication.
• These are then subjected to Lyophilization to promote an
irreversible adsorption of carbohydrate onto the ceramic
surface.
• The unadsorbed carbohydrate is removed by centrifugation.
• The commonly used coating materials are Cellobiose, citrate,
pyridoxal-5- phosphate, Trehalose and sucrose.
• Core to coat ratio of 1:4 or 1:5 caused formation of spherical
coated particles. 47
7/2/2023

III. LOADING OF THE DRUG OF CHOICE TO THIS
ASSEMBLY
• The final stage involves the loading of drug to the coated
particles by adsorption.
• For that, a solution of known concentration of drug is prepared
in suitable pH buffer, and coated particles are dispersed into it.
• The dispersion is then either incubated at low temperature for
drug loading or lyophilized after some time so as to obtain the
drug-loaded formulation (i.e., aquasomes).
• The preparation thus obtained is then characterized using
various techniques. 48
7/2/2023

APPLICATIONS OFAQUASOMES
1. Insulin delivery
2. Oral delivery of acid labile enzyme
3. As oxygen carrier
4. Antigen delivery
5. Delivery of drug
6. For delivery of gene
7. For delivery of enzymes
8. Miscellaneous
49
7/2/2023

50
7/2/2023

PHYTOSOMES
• The term ‘Phyto’ means plant while ‘Some’ means cell-like.
• Phytosome is a vesicular drug delivery system in which
phytoconstituents of herbal extract surround and bound by
lipids (one phyto-constituent molecule linked with at least
one phospholipid molecule).
• Phytosome protect valuable component of herbal extract from
destruction by digestive secretion and gut bacteria and
because of which they shows better absorption which
produces better bioavailability and improved
pharmacological and pharmacokinetic parameters than
conventional herbal extract.
51
7/2/2023

52
7/2/2023

ADVANTAGES OF PHYTOSOME
• Phytosome is much better absorbed than liposome because
drug is in complex form with lipid.
• Leakage of drug during storage does not occur in
phytosome, because drug is bonded with lipid, however loss
may occur due to some chemical degradation i.e. hydrolysis.
• Phosphatidylcholine used in preparation of phytosomes,
besides acting as carrier also act as a hepatoprotective.
• The physiochemical stability of phytosome depends upon
the physicochemical properties of drug-lipid complex.
• Application of phytpconstituent in form of phytosome
improve their percutaneous absorption and as functional
cosmetics. 53
7/2/2023

DISADVANTAGE OFPHYTOSOMES
• 1) Regarding all advantages phytosome may rapidly
exclude the phytoconstituent
• 2) phospholipid can encourage proliferation on MCF-7
breast cancer cell line.
• 3) Phytosomes predominant limitation is reported as
leaching of the phytoconstituent off the some which
• reduced the anticipated drug concentration
54
7/2/2023

APPLICATION OFPHYTOSOMES
1) Enhancing Bioavailability
2) Delivery of large and diverse drugs, eg. peptides and
proteins
3) Safe composition
4) Hepato-Protective
5) Approved for cosmetic and
6) pharmaceutical applications
7) Low-risk profile
8) Toxicological properties have been well documented
9) High market attraction
55
7/2/2023

PREPARATION OFPHYTOSOMES:
1. Active constituent of herbal extract+ Phospholipid is
mixed in aprotic solvent for complex formation with
constant stirring.
2. Complex is isolated with addition of non solvent
Complex in drying form
3. Complex dissolve in organic solvent
4. Drying
5. Thin Film Formation
6. Hydration of thin film
7. Formation of phytosome complex (suspension)
8. Isolation by precipitation with non solvent (such as
aliphatic hydrocarbons)
9. Drying (By lyophilization or spray drying)
56
7/2/2023

57
7/2/2023

ELECTROSOME
• Is a novel surface-display system based on the specific
interaction between the cellulosomal scaffoldin protein
and a cascade of redox enzymes that allows multiple
electron release by fuel oxidation.
The electrosome is composed of two compartments:
(i) Hybrid Anode, which consists of dockerin-containing
enzymes attached specifically to cohesin sites in the
scaffoldin to assemble an ethanol oxidation cascade, and
(ii) Hybrid Cathode, which consists of a dockerin-
containing oxygen-reducing enzyme attached in multiple
copies to the cohesin-bearing scaffoldin
58
7/2/2023

PREPARATION
Strains and construct method
Enzyme binding to scaffoldin
Biofuel cell assembly and characterisation
Protein expression
Enzyme activity assays
Application
1) They use enzymatic reactions to catalyze the conversion of
chemical energy to electricity in a fuel cell.
2) The use of enzymatic cascades in enzymatic fuel cell anodes
resulted in very high power outputs, as the electron density
achieved was much higher when the fuel was fully oxidized. 59
7/2/2023

REFERENCE
1. Xuemei Ge, Minyan Wei, Suna He and Wei-En Yuan,
Advances of Non-Ionic Surfactant Vesicles (Niosomes)
and their application in Drug Delivery, Journal of
Pharmaceutics. 2019;Vol 11(15): Pg no. 1-16.
2. S.P Vyas, R.K.Khar, Targeted and Controlled Drug
Delivery Novel Carrier Systems, CBS Publishers and
Distributors. Pg no. 249-259.
3. Sritoma Banerjee, Kalyan Kumar Sen, Aquasomes: A
novel nanoparticulate drug carrier, Journal of Drug
Delivery Science and technology. 2018; Vol 43: Pg no.
446-452.
60
7/2/2023

REFERENCE
5. M.Sravanthi and J.Shiva Krishna, Phytosomes : A novel
Drug Delivery for Herbal Extracts, International Journal
of Pharmaceutical Sciences and Research. 2013;
Vol.4(3): Pg no. 949-959.
6. Alon Szczupak , Dror Aizik , Sarah Morais , Yael
Vazana, Yoav Barak, Edward A. Bayer et al., The
Electrosome: A Surface-Displayed Enzymatic Cascade in
a Biofuel Cell’s Anode and a High-Density Surface-
Displayed Biocathodic Enzyme, Journal of
Nanomaterials. 2017; Vol 7(153) Pg 1-17.
61
7/2/2023

62
7/2/2023

RATHNA MP.pptx

Recommended

Recommended

More Related Content

Similar to RATHNA MP.pptx

Similar to RATHNA MP.pptx (20)

More from ManojKumarr75

More from ManojKumarr75 (14)

Recently uploaded

Recently uploaded (20)

RATHNA MP.pptx

Editor's Notes