Shakti Emulsion

PREPARED BY: SUTHAR SHAKTI

M.PHARM PHARMACEUTICS

CONTENTS:

RECENT ADVANCE IN EMULSION

Multiple emulsion Microemulsion Self emulsifying drug delivery

system Nanoemulsion

04/11/23Shakti Suthar

Multiple emulsion


Contents: Introduction Method of preparation Characterization of Multiple emulsion Application


Introduction:

Multiple emulsion systems are novel developments in the field of emulsion technology and are more complex type of dispersed system.

These are the emulsion systems in which the dispersed phase contain smaller droplets that have the same compositon as the external phase.

These made possible by the double emulsification hence the systems are also called as “double emulsion”.

Diameter of the droplets in a Multiple emulsion is in the range of o.5 to 3µm.


Like simple emulsion multiple emulsion are classified into two type.

1)O/W/O type 2)W/O/W type The immiscible phase ,which separates

the two miscible phase is known as “liquid membrane” and act as a diffusion barrier and semipermeable membrane for drugs or moities entrapped in the internal aqueous phase.


Methods of preparation

Multiple emulsion systems can be formed by the reemulsification of a primary emulsion or they can be produced when an emulsion inverts from one type to another,eg.W/O to O/W.

Three methods for preparation: 1)Two step emulsification(Double

emulsification) 2)Phase inversion technique(One step

technique) 3)Membrane emulsification technique


1)Two step emulsification: First prepare primary emulsion (W/O or O/W ) Then it is reemulsified with an excess of

aqueous or oil phase.2)Phase inversion technique: Aqueous phase containing hydrophilic

emulsifier is added into the oil phase containing the lipophilic surfactant in a mixer at a rate of 5ml/min.

The mixer is rotate at 88rpm at room temperature.

When volume fraction of aqueous solution containing hydrophilic emulsifier exceeds 0.7, the continuous oil phase is converted into aqueous phase containing number of small oil droplets.


3)Membrane emulsification technique In this method a W/O

emulsion(dispersed phase) is extruded into a an external aqueous phase(continuous phase) with a constant pressure through a porous glass membrane which should have controlled and homogenous pores.

The relationship between membrane pore size and droplet size of W/O/W emulsion is given by following equation :

Y=5.03X + O.1904/11/23Shakti Suthar

Characterization of Multiple emulsion : 1)Macroscopic examination: Colour Consistency Homogeneity 2)Average globule size and size

distribution: By using optical microscopy or phase

contrast microscop. By this technique, they are classified into 1)Course(>3 µm diameter) 2)Fine (1-3 µm diameter) 3)Micro-multiple emulsion (<1 µm

diameter) 04/11/23Shakti Suthar

3) Area of interfaces:The average globule diameter

determine can be used in the calculation of the total area of interface using the formula:

S= 6 / d

4) Rheological evaluation:It include 2 parameters:1.Viscosity (By brookfield viscometer )2.Interfacial film strength (By

Oscillatory surface rheometer)04/11/23Shakti Suthar

5) Zeta potential measurement: This is used to identify the charge of the

droplets. It can be calculated by following equation:

ᶎ = 4ᴨῃụ * 103

ᵋE6) In vitro drug release:By dialysis method using cellophane tubing.


Application :Controlled and sustained drug delivery.Drug targeting.Vaccine adjuvant . Immobilization of enzyme.Cosmetic application.As a preparative tool for

microencapsulation technology.Miscellaneous. Protection action. Taste masking. Absorption enhancement through

GIT.04/11/23Shakti Suthar

Microemulsion


Contents:

Introduction Advantages Disadvantages Diffference Preparation Evaluation Research work


Introduction: Microemulsions are clear, stable, liquid mixtures

of oil, water and surfactant, frequently in combination with a cosurfactant like short chain alcohol or amine.

Diameter of the droplets in a microemulsion is in the range of 0.1 to 10 µm.

The two basic types of microemulsions are

(1) o/w (oil dispersed in water) and

(2) w/o (water dispersed in oil).


Advantages: Thermodynamically stable Act as a supersolvents of drug. Diameter of droplets is less so they can

be sterilized by filtration. Due to small droplets,they have large

interfacial area so the absorption of drug is more.

Same microemulsion can carry both lipophilic and hydrophilic drugs.

Because of thermodynamic stability,they are easy to prepare and require less energy during their preparation.

Formation of microemulsion is reversible.


Disadvantages: Use of large concentration of surfactant

and cosurfactant necessary for solubilizing the nanodroplets.

Limited solubilizing capacity for high melting substances.

The surfactant must be non toxic for using pharmaceutical application.

Microemulsion stability is influenced by environmental parameters such as temperature and pH. These parameters change upon microemulsion delivery to patients.


Difference between Ordinary emulsion and Microemulsion:

Ordinary emulsion

Microemulsion

Size of globule: 0.5-50 µm 0.1-10 µm

Appearance: Turbid Clear

Thermodynamically: Stable but coalesce finally.

More stable

Viscosity: - Less compared to other emulsion.

Preparation:

It require high shear condition

By simple mixing of the component and do not require high shear condition

Surfactant concentration: 2-3 %Waight 6-8 %Waight

Phases: 2 1



Preparation of microemulsion: Microemulsions are thermodynamically

stable, so they can prepared simply by blending oil, water, surfactant and cosurfactant with mild agitation or mild heat.

Titrating the mixer of surfactant ,cosurfactant,and oil against the water till the clear solution is obtained.

If solution is still slight turbid then add some more amount of cosurfactant to get the clear solution.



Evaluation of microemulsion1)Percentage Transmittance:

Transparency of microemulsion formulation was determined by measuring percentage transmittance through U.V. Spectrophotometer.

2)Droplet Size Analysis: By microscopic method3)Zeta-Potential Determination:4)Viscosity5)Conductivity Measurements6)Stability Studies: The optimized ME was stored at three different temperature ranges for 6 months

i.e., refrigerating condition (20C – 80C), room

temperature and elevated temperature (50 ± 20C) and shelf life of the stored microemulsion system was evaluated by visual inspection (phase separation), % transmittance, Particle size and % Assay.


Research Work carried out on Microemulsions Drug Name Route

Purpose/Result Flurbiprofen Parenteral Increased the solubility Apormorphine HCl Transdermal Increased the permeability Ketoprofen Transdermal Enhancement of

permeability Prilocainne-HCL Transdermal Increased the solubility Estradiol Transdermal Improvement in

solubilization Aceclofenac Dermatological Increased the

solubility Piroxicam Oral Increased the

solubility Diclofenac Transdermal Permeability

enhancement Dexamethasone Topical Ocular Enhanced the Bioavailability Chloramphenicol Ocular Increased the solubility Ibuprofen Parenteral Increased the solubility Sumatriptan Intranasal Enhanced the

Bioavailability Ibuprofen Topical Increasing the

solubility


SELF EMULSIFYING DRUG DELIVERY

SYSTEM


Contents:

Introduction Need of SEDDS Composition of SEDDS Formulation of SEDDS Characterization of SEDDS Application Drawback


Introduction:

Self-emulsifying drug delivery systems (SEDDS) are usually used to improve the bioavailability of hydrophobic drugs.

Approximately 40% of new chemical entities exhibit poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low bioavailability.

SEDDS is ideally an isotropic mixture of oils and surfactants and sometimes co solvents.

The multi-component delivery systems have optimized by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation, and by determination of particle size of the resulting emulsion.


Upon oral administration,these systems form fine (micro) emulsions in the gastrointestinal tract (GIT) with mild agitation provided by gastric mobility.

Fine oil droplets would pass rapidly from the stomach and promote wide distribution of the drug throughout the GI tract, thereby minimizing the irritation frequently encountered during extended contact between bulk drug substances and the gut wall.

When compared with emulsions, which are sensitive and metastable dispersed forms, SEDDS are physically stable formulations that are easy to manufacture.


Need of SEDDS:

Oral delivery of poorly water-soluble compounds is to pre-dissolve the compound in a suitable solvent and fill the formulation into capsules.

The main benefit of this approach is that pre-dissolving the compound overcomes the initial rate limiting step of particulate dissolution in the aqueous environment within the GI tract.


Composition of SEDDS:

1)Oils. 2)Surfactant 3)Cosolvents 4)Medicament


1)Oils: Oils can solubilize the lipophilic drug in a specific

amount. It is the most important excipient because it can

facilitate self-emulsification and increase the fraction of lipophilic drug transported via the intestinal lymphatic system, thereby increasing absorption from the GI tract.

Mainly triglycerides are use.

2)Surfactant: Nonionic surfactants with high hydrophilic–

lipophilic balance (HLB) values are used in formulation of SEDDSs.


The usual surfactant strength ranges between 30–60% w/w of the formulation in order to form a stable SEDDS

e.g., Tween, Labrasol, Labrafac CM 10, Cremophore, etc.).

3)Cosolvents: It may help to dissolve large amounts of hydrophilic

surfactants or the hydrophobic drug in the lipid base. These solvents sometimes play the role of the cosurfactant in the microemulsion systems.

Eg.diehylene glycol monoethyl ether (transcutol), propylene glycol, polyethylene glycol, polyoxyethylene, propylene carbonate, tetrahydrofurfuryl alcohol,polyethylene glycol ether (Glycofurol), etc.


Formulation of SEDDSs: The following should be considered in the

formulation of a SEDDS: The solubility of the drug in different oil,

surfactants and cosolvents. The selection of oil, surfactant and cosolvent based

on the solubility of the drug and the preparation of the phase diagram.

For preparation following steps are involve

1) Preparation of phase diagram

2) Solubilizing a poorly water-soluble drug and/or pharmaceutical ingredient, in a mixture of surfactant, cosurfactant and solvent.


Now mix the oil phase suitably prepared, if necessary,by heating or other preparatory means, to the solubilized drug formulation and thoroughly mixed.

3) The emulsion can then be added to a

suitable dosage form such as soft or hard-filled gelatin capsules and allowed to cool.


Characterization of SEDDSs: Visual assessment. This may provide important

information about the self-emulsifying and microemulsifying property of the mixture and about the resulting dispersion.

Turbidity Measurement. This is to identify efficient

self-emulsification by establishing whether the dispersion reaches equilibrium rapidly and in a reproducible time.

Droplet Size. This is a crucial factor in self-emulsification performance because it determines the rate and extent of drug release as well as the stability of the emulsion. Photon correlation spectroscopy, microscopic techniques or a Coulter Nanosizer are mainly used for the determination of the emulsion droplet size. The reduction of the droplet size to values below 50 μm leads to the formation of SMEDDSs, which are stable and clear o/w dispersions.


Zeta potential measurement. This is used to identify the charge of the droplets. In conventional SEDDSs, the charge on an oil droplet is negative due to presence of free fatty acids.

Determination of emulsification time. Self-emulsification time, dispersibility, appearance and flowability was observed.


Applications Improvement in Solubility and

bioavailability. Eg. Ketoprofen Protection against Biodegradation Eg .Aspirin Drawbacks of SEDDS Chemical instabilities of drugs and high

surfactant concentrations. The large quantity of surfactant in self-emulsifying formulations (30-60%) irritates GIT. Consequently, the safety aspect of the surfactant vehicle had to be considered.

Volatile cosolvents in the conventional self-emulsifying formulations are known to migrate into the shells of soft or hard gelatin capsules, resulting in the precipitation of the lipophilic drugs.


NANOEMULSION


Contents:

Introduction Advantages Method of preparation Characterization Marketed products Patented NE Application


Introduction:

Nanoemulsion are thermodynamically stable system in which the two immisible liquid (water and oil)are mix to form a single phase by means of appropriate surfactant .

Diameter of the droplets in a nanoemulsion is in the range of 20 to 200 nm.


Advantages: High surface area and free energy then

macroemulsion that make them effective transport system.

NEs do not show the problem of creaming, flocculation, coalescence and sedimentation which are associated with macroemulsion.

It can be formulated in variety of formulation such as foam,spray,cream,liquid etc.

NEs are non toxic and non irritant so they can be easily applied to skin and mucous membrane.

NEs are formulated by the surfactant which are approved by the GRAAS,so they can be given by the enteric route.

NEs do not damage the animal and human cells hence are suitable for human and veterinary purpose


Method of preparation of NEs1)High pressure homoginization: By high pressure homoginizer or piston

homoginizer which produce NEs of exrtemly low particle size upto 1 nm.

2)Microfluidization: This make use of microfluidizer. This device use high pressure positive

displacement pump(500-20000 psi) which force the product through the interaction chamber which consist of small micro channel.

Product flow throgh the micro channel on to the impigment resulting in the formation of nano size droplet. 04/11/23Shakti Suthar


Characterization of NEs:

Transmission eletron microscopy Drolet size analysis Viscosity Refractive index Skin irritation test Thermodynamic stability study Surface characteristics


Marketed products:

Drug Brand Manufacturer Indication

Propofol Diprivan Astra zeneca Anesthatic

Dexamethazone

Limethasonn Mitsubishi pharmaceutical, Japan

Steroids

Palmitate alprostadil

Liple Mitsubishi pharmaceutical, Japan

Vasodilator

Flubriprofen axetil

Ropion Kaken pharmaceutical, Japan

NSAIDS

Vitamines A,D,E,K

Vitalipid Fresenius kabi,Europe

Parenteral nutrition


Patented nanoemulsions:

Patent name:Method of preventing and treating microbial infection.Assigne: nano bio corporation US.Patent no-6506803.

Patent name:NE based on phosphoric acid fatty ester and use in cosmetics. Assigne:L,orial(Paris) US.Patent no-6275150.

Patent name:NE based on ethylene oxide and propylene oxide.


Application: Use in cosmetics As a antimicrobial nanoemulsion Use in cell culture technology As a non toxic disinfectant cleaner Use in cancer therapy For improved oral delivery of poorly

soluble drugs. As a vehicle for transdermal delivery


References: 1)Advances in controlled and novel drug

delivery. By N.K.Jain2)Targeted and controlled drug delivery By S.P.Vyas and R.K.Khar3)Nano emulsion: A pharmaceuticle review. http:/www.sysrevpharm.org4) Review Article :Microemulsions: a novel

drug carrier system.International Journal of Drug Delivery Technology 2009; 1(2): 39-41 www.ijddt.com


5) Self emulsifying drug delivery system: an approach to enhance bioavailability International Journal of Pharma Research and Development – Online

www.ijprd.com 6) TOPICAL REVIEW: nanoemulsions: Formation, structure, and physical

properties. Journal of physics: condensed matter 18 (2006) r635–r666

Stacks.Iop.Org/jphyscm/18/R633


Study question:

Write a note on Self-emulsifying drug delivery systems. (GTU-remidial December 2010)

