1. Liposomes are spherical vesicles made of phospholipid bilayers that can encapsulate aqueous content. They range in size from 20nm to micrometers.
2. Liposomes are composed mainly of phospholipids and cholesterol. Commonly used phospholipids include phosphatidylcholine, phosphatidylethanolamine, and dioleoyl phosphatidylcholine. Cholesterol helps stabilize the bilayer structure.
3. Liposomes offer advantages like low toxicity, biodegradability, protection of encapsulated drugs, and improved pharmacokinetics. However, they also have disadvantages such as drug leakage, short half-life, high production costs, and difficulty in large-scale manufacturing
Introduction
Structure
Niosomes Vs. Liposome
Advantages & Disadvantages
Properties of Niosomes
Method of Manufacturing
Evaluation of Niosomes
Applications
Marketed products
Liposomes-Classification, methods of preparation and application Vijay Hemmadi
liposome preparation and application
A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Membranes are usually made of phospholipids, which are molecules that have a head group and a tail group
Liposomes, Structure of liposome, phospholipids, classification of liposomes, method of preparation of liposomes, mechanism of liposome formation, application of liposomes.
Introduction
Structure
Niosomes Vs. Liposome
Advantages & Disadvantages
Properties of Niosomes
Method of Manufacturing
Evaluation of Niosomes
Applications
Marketed products
Liposomes-Classification, methods of preparation and application Vijay Hemmadi
liposome preparation and application
A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Membranes are usually made of phospholipids, which are molecules that have a head group and a tail group
Liposomes, Structure of liposome, phospholipids, classification of liposomes, method of preparation of liposomes, mechanism of liposome formation, application of liposomes.
‘Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells.’
NIOSOMES , GENERAL CHARACTERISTICS OF NIOSOME , TYPES OF NIOSOMES , OTHERS TYPES OF NIOSOMES , NIOSOMES VS LIPOSOMES , COMPONENTS OF NIOSOMES , Non-ionic surfactant , Cholesterol , Charge inducing molecule , METHOD OF PREPARATION , preparation of small unilamellar vesicles , Sonication , Micro fluidization , preparation of large unilamellar vesicles , Reverse Phase Evaporation , Ether Injection , preparation of Multilamellar vesicles , Hand shaking method , Trans membrane pH gradient drug uptake process (remote loading) , Miscellaneous method :Multiple membrane extrusion method , The “Bubble” Method , Formation of Niosomes From Proniosomes , SEPARATION OF UNENTRAPPED DRUGS , Gel Filtration , Dialysis , Centrifugation , FACTORS AFFECTING THE PHYSICOCHEMICAL PROPERTIES OF NIOSOMES , Membrane Additives , Temperature of Hydration , PROPERTIES OF DRUGS , AMOUNT AND TYPE OF SURFACTANT
Structure of Surfactants , Resistance to Osmotic Stress , Characterization of niosomes ,Therapeutic applications of Niosomes , For Controlled Release of Drugs , To Improve the Stability and Physical Properties of the Drugs , For Targeting and Retention of Drug in Blood Circulation , Proniosomes , Aspasomes , Vesicles in Water and Oil System (v/w/o) ,Bola - niosomes , Discomes , Deformable niosomes or elastic niosomes , According to the nature of lamellarity ,Small Unilamellar vesicles (SUV) 25 – 500 nm in size.,Large Unilamellar vesicles (LUV) 0.1 – 1μm in size , Multilamellar vesicles (MLV) 1-5 μm in size , According to the size:Small Niosomes (100 nm – 200 nm) , Large Niosomes (800 nm – 900 nm),Big Niosomes (2 μm – 4 μm)
Mucoadhesive drug delivery system interact with the mucus layer covering the mucosal epithelial surface, & mucin molecules & increase the residence time of the dosage form at the site of the absorption.
Mucoadhesive drug delivery system is a part of controlled delivery system.
Since the early 1980,the concept of Mucoadhesion has gained considerable interest in pharmaceutical technology.
combine mucoadhesive with enzyme inhibitory & penetration enhancer properties & improve the patient complaince.
MDDS have been devloped for buccal ,nasal,rectal &vaginal routes for both systemic & local effects.
Hydrophilic high mol. wt. such as peptides that cannot be administered & poor absorption ,then MDDS is best choice.
Mucoadhesiveinner layers called mucosa inner epithelial cell lining is covered with viscoelasticfluid
Composed of water and mucin.
Thickness varies from 40 μm to 300 μm
General composition of mucus
Water…………………………………..95%
Glycoproteinsand lipids……………..0.5-5%
Mineral salts……………………………1%
Free proteins…………………………..0.5-1%
The mechanism responsible in the formation of mucoadhesive bond
Step 1 : Wetting and swelling of the polymer(contact stage)
Step 2 : Interpenetration between the polymer chains and the mucosal membrane
Step 3 : Formation of bonds between the entangled chains (both known as consolidation stage)
Electronic theory
Wetting theory
Adsorption theory
Diffusion theory
Fracture theory
Advantages over other controlled oral controlled release systems by virtue of prolongation of residence of drug in GIT.
Targeting & localization of the dosage form at a specific site
-Painless administration.
-Low enzymatic activity & avoid of first pass metabolism
If MDDS are adhere too tightlgy because it is undesirable to exert too much force to remove the formulation after use,otherwise the mucosa could be injured.
-Some patient suffers unpleasent feeling.
-Unfortunately ,the lack of standardized techniques often leads to unclear results.
-costly drug delivery system
‘Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells.’
NIOSOMES , GENERAL CHARACTERISTICS OF NIOSOME , TYPES OF NIOSOMES , OTHERS TYPES OF NIOSOMES , NIOSOMES VS LIPOSOMES , COMPONENTS OF NIOSOMES , Non-ionic surfactant , Cholesterol , Charge inducing molecule , METHOD OF PREPARATION , preparation of small unilamellar vesicles , Sonication , Micro fluidization , preparation of large unilamellar vesicles , Reverse Phase Evaporation , Ether Injection , preparation of Multilamellar vesicles , Hand shaking method , Trans membrane pH gradient drug uptake process (remote loading) , Miscellaneous method :Multiple membrane extrusion method , The “Bubble” Method , Formation of Niosomes From Proniosomes , SEPARATION OF UNENTRAPPED DRUGS , Gel Filtration , Dialysis , Centrifugation , FACTORS AFFECTING THE PHYSICOCHEMICAL PROPERTIES OF NIOSOMES , Membrane Additives , Temperature of Hydration , PROPERTIES OF DRUGS , AMOUNT AND TYPE OF SURFACTANT
Structure of Surfactants , Resistance to Osmotic Stress , Characterization of niosomes ,Therapeutic applications of Niosomes , For Controlled Release of Drugs , To Improve the Stability and Physical Properties of the Drugs , For Targeting and Retention of Drug in Blood Circulation , Proniosomes , Aspasomes , Vesicles in Water and Oil System (v/w/o) ,Bola - niosomes , Discomes , Deformable niosomes or elastic niosomes , According to the nature of lamellarity ,Small Unilamellar vesicles (SUV) 25 – 500 nm in size.,Large Unilamellar vesicles (LUV) 0.1 – 1μm in size , Multilamellar vesicles (MLV) 1-5 μm in size , According to the size:Small Niosomes (100 nm – 200 nm) , Large Niosomes (800 nm – 900 nm),Big Niosomes (2 μm – 4 μm)
Mucoadhesive drug delivery system interact with the mucus layer covering the mucosal epithelial surface, & mucin molecules & increase the residence time of the dosage form at the site of the absorption.
Mucoadhesive drug delivery system is a part of controlled delivery system.
Since the early 1980,the concept of Mucoadhesion has gained considerable interest in pharmaceutical technology.
combine mucoadhesive with enzyme inhibitory & penetration enhancer properties & improve the patient complaince.
MDDS have been devloped for buccal ,nasal,rectal &vaginal routes for both systemic & local effects.
Hydrophilic high mol. wt. such as peptides that cannot be administered & poor absorption ,then MDDS is best choice.
Mucoadhesiveinner layers called mucosa inner epithelial cell lining is covered with viscoelasticfluid
Composed of water and mucin.
Thickness varies from 40 μm to 300 μm
General composition of mucus
Water…………………………………..95%
Glycoproteinsand lipids……………..0.5-5%
Mineral salts……………………………1%
Free proteins…………………………..0.5-1%
The mechanism responsible in the formation of mucoadhesive bond
Step 1 : Wetting and swelling of the polymer(contact stage)
Step 2 : Interpenetration between the polymer chains and the mucosal membrane
Step 3 : Formation of bonds between the entangled chains (both known as consolidation stage)
Electronic theory
Wetting theory
Adsorption theory
Diffusion theory
Fracture theory
Advantages over other controlled oral controlled release systems by virtue of prolongation of residence of drug in GIT.
Targeting & localization of the dosage form at a specific site
-Painless administration.
-Low enzymatic activity & avoid of first pass metabolism
If MDDS are adhere too tightlgy because it is undesirable to exert too much force to remove the formulation after use,otherwise the mucosa could be injured.
-Some patient suffers unpleasent feeling.
-Unfortunately ,the lack of standardized techniques often leads to unclear results.
-costly drug delivery system
liposomes are novel drug delivery dosage systems, where the drug is entrapped in phospholipid bilayered vesicles. the release of drug from the vesicles can be controlled or sustained.
the follwing presentation contain structure, classification and preparation methods, characterization and applications of liposomes.
Niosomes are vesicles composed mainly of hydrated non-ionic surfactant with or without cholesterol used for targetted drug delivery. Niosomes are better than liposomes as they are cost effective, stable, and can be stored for a long period of time.
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The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
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1. A GRADED SEMINAR ON
Presented By- Guided By-
Atish Khilari Dr.(Mrs).Shilpa Chaudhari
M.Ph (2nd sem.)
Pharmaceutics
D.Y
Dr. D. Y. Patil College of Pharmacy,Akurdi,pune-44
5. INTRODUCTION
DEFINITION :
Liposomes are concentric bilayered vesicles in which an aqueous volume
is entirely enclosed by a membranous lipid bilayer mainly composed of
natural or synthetic phospholipids.
Liposome were first produced in England in 1961 by Alec D. Bangham
The size of a liposome ranges from 20 nm up to several micrometers.
Phospholipid bilayer
Aqueous phase
5
Fig.1-Structure of liposomes
8. PHOSPHOLIPIDS
• Phospholipids are the major structural components
of biological membranes such as the cell membrane.
Two types of Phospholipids
(along with their hydrolysis
products)
Phosphoglycerides
Sphingolipids
8
9. PHOSPHOLIPIDS
Phospholipids are major structural
components of biological membranes in
human body, where 2 types of
phospholipids exist i.e.
phosphoglycerides & sphingolipids.
Each phospholipid molecule has 3
major parts, 1 head & 2 tails. Head is
made from 3 molecular components:
choline , phosphate & glycerol which is
hydrophilic. Each tail with a long chain
which are hydrophobic.
9
Fig.2- phospholipids
11. CHOLESTEROL
• Cholesterol stabilizes the membrane.
• It plays important role in bilayer formation.
• Cholesterol by itself does not form bilayer structure.
• Cholesterol act as fluidity buffer.
• Enhances the stability of the membrane.
• Enhances the rigidity of the phospholipid bilayer.
• Reduces the permeability of water soluble substance through the
membrane. 11
12. ADVANTAGES
Non-toxic.
Biodegradable.
Increased stability of encapsulated drugs.
Lowers systemic toxicity.
Site avoidance effect (avoids non-target tissues).
Protection of sensitive drug molecules.
Improved pharmacokinetic effects. 12
13. DISADVANTAGES
• Leakage of encapsulated drug during storage.
• Short half-life.
• Batch to batch variation.
• Difficult in large scale manufacturing and sterilization.
• Production cost is high.
• Once administered, liposomes can not be removed.
• Sometimes phospholipids undergoes hydrolysis and oxidation
reactions.
13
14. CLASSIFICATION:
VESICLE TYPE ABBREVIATION DIAMETER SIZE NO. OF LIPID BI -
LAYER
Unilamellar vesicle UV All size range ONE
Small unilamellar vesicle SUV 20-100 nm ONE
Medium unilamellar vesicle MUV >100µm ONE
Large unilamellar vesicle LUV >1000µm ONE
Giant unilamellar vesicle GUV >1µm ONE
Oligolamellar vesicle OLV 0.1-1µm 5
Multilamellar vesicle MLV >0.5µm 5-25
Multivesicular vesicle MV >1µm Multicompartmental
structure 14
17. MECHANICAL DISPERSION METHOD:
Hand-shaking method:
1
• This is one of the simplest method for preparation of liposomes.
• The surfacant /cholesterol mixture is dissolves in diethyl ether in
RBF.
2
• Organic solvent is then removed at room temp. under reduced
pressure.
3
• After releasing vaccum, the flask is flushed with nitrogen then
flask is attached to rotary evaporator rotated at room
temprature at 60 rpm.
4
• The dried surfactant film is hydrated with an aqueous phase at
50°c to 60°c during gentle agitation.
5 • Large multilamellar vesicles are formed.
17
20. BATH SONICATOR PROBE SONICATOR
1.Large volume of diluted lipids
are processed.
1.Small volume of diluted lipids
are processed.
2.Less or no contamination. 2.Chances of contamination.
• At high energy levels, average size of vesicles is further reduced.
• Exposure of MLV’s to ultrasonic irradiations is the most widely
used method for producing small vesicles.
• As chances of contamination are likely to occur in probe sonicator,
bath sonicator is widely used.
20
21. FRENCH PRESSURE CELL
• Construction:
• The french pressure cell is
constructed from stainless
steel and is capable of
withstanding very high
pressures, even up to 20,000
- 40,000 psi.
• The body of the cell
contains a pressure chamber,
an outlet, a piston, bottom
seal, etc. both the piston and
the bottom seal contain an
O-ring each, which enables
in tight sealing the pressure
cell. 21Fig.4- French pressure cell.
22. Working:
(i) Initially the liposome suspension is added to the pressure cell and
piston is pushed into the body. Then the entire cell is turned
upside down i.e., by an angle of 180 ͦ.
(ii) The liquid sample is then filled in the entire cavity till the outlet.
(iii) After filling, the bottom seal is pressed down and the pressure
cell is closed.
(iv) The cell is brought back to upright position and the pressure is
developed in the cell using a hydraulic press.
(v) After sufficient pressure has been developed in the pressure cell,
the valve is opened very slowly and the product is allowed to exit in
a drop-wise manner.
22
23. FREEZE THAW SONICATION(FTS):
Freeze SUV dispersion
Thaw at room temperature for 15 minutes
Sonicate
Rupture of SUV’s occur
Formation of liposomes.
23
24. SOLVENT DISPERSION METHODS
I) ETHANOL INJECTION METHOD:
Lipids ethanol
Rapidly inject through a fine needle
Saline buffer containing materials to be entrapped
dissolution of ethanol
Formation of SUV’s.
24Fig.5- Ethanol injection method.
25. II) ETHER INJECTION METHOD:
Lipid ether
Slowly injecting through a narrow needle
Vapourize temperature at 60˚C
Production of SUV’s.
• Less risk of oxidation as ether is free of peroxides.
• Low efficiency.
• Long time needed for production. 25
26. REVERSE PHASE EVAPORATION VESICLES
Lipid organic solvent aqueous solution
Mix
Sonicate
Formation of w/o emulsion
Evaporate to remove the organic solvent
Lipids form a phospholipid bilayer
Vigorous shaking
Water droplets collapse
Formation of LUV’s.
26
27. STABILITY OF LIPOSOMES:
A. PREVENTION OF CHEMICAL DEGRADATION:
1. Start with freshly purified lipids & freshly distilled solvents.
2. Avoid procedure which involving high temperature.
3. Carry out manufacturing in the absence of oxygen.
4. Deoxygenate aqueous solution with nitrogen.
5. Store liposome suspension in an inert atmosphere.
6. Include an antioxidant as a component.
27
28. STABILITY OF LIPOSOMES:
B. PREVENTION OF PHYSICAL DEGRADATION:
1.‘ANNEALING’ is best method to control physical
degradation i.e incubating the liposomes at a temperature high
enough above the phase transition temperature.
2. The stability of liposomes may also be increased by cross
linking membrane component covalently using Gluteraldehyde
fixation, osmification or polymerization of alkyne containing
phospholipids.
These methods increases mechanical strength of the membrane
& render them less susceptible to disruption.
28
29. CHARACTERIZATION:
Size & its distribution:-
• Electron microscopy is most specific method to determine size
of liposome since it allows us to view individual liposome &
to obtain exact information about profile of liposome
population over the whole range of size. laser light scattering
method is very simple.
Surface charge-
• Free-flow electrophoresis on a cellulose acetate plate in a
sodium borate buffer pH 8.8
• The samples are applied to plate & electrophoresis is carried
out at 4˚C for 30 min.
• The plate is dried and phospholipids are visualised by the
molybdenum blue reagent.
• The liposomes get bifurcated based on the surface charge. 29
30. Percent drug entrapment-
• This can be determined by ‘PROTAMINE AGGREGATE’
& ‘MINICOLUMN CENTRIFUGATION’ method.
Expressed as % entrapment/mg lipid.
Phase behaviour-
• Liposomes at transition temperature undergo reversible phase
transition i.e the polar head groups in gel state become
disordered to form the liquid crystalline state which can be
determined by DSC.
Lamellarity-
• The average no. of bilayers present in liposomes can be find
out by freeze electron microscopy & 31 p-NMR. Now-a-days
freeze fracturing electron microscopy has become a very
popular method to study structural details of aqueous lipid
dispersion. 30
31. APPLICATIONS
• Liposomes as drug or protein delivery vehicles.
• Liposome in antimicrobial, antifungal(lung therapeutics) and antiviral (anti
HIV) therapy.
• In tumor therapy.
• In gene therapy.
• In immunology.
• Liposomes as artificial blood surrogates.
• Liposomes as radio pharmaceutical and radio diagnostic carriers.
• Liposomes in cosmetics and dermatology.
31
