The document summarizes information on microemulsions and self-emulsifying drug delivery systems. Microemulsions are thermodynamically stable dispersions of oil and water stabilized by surfactants that can solubilize both water-soluble and oil-soluble compounds. They form nanometer-sized droplets through the addition of surfactants and sometimes cosurfactants. Microemulsions have advantages over other dosage forms like increased absorption and bioavailability of drugs. Their components include oils, surfactants, and an aqueous phase, with cosurfactants sometimes used to aid formation.
SOLID DISPERSION
Definition: The technology is the science of dispersing one or more active ingredients in an inert matrix in the solid stage.
Need of solid dispersion:
Increases Oral bioavailability of a drug
Increased dissolution rate.
Enhanced release of drugs from ointment.
Improved the solubility & stability.
The concept of solid dispersion was originally proposed by Sekiguchi & obi.
Increasing the dissolution, absorption & therapeutic efficacy of drugs in dosage forms.
Increasing solubility in water.
Improving the oral absorption and bioavailability of BCS Class II drugs.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
Factors affecting sustained release drug delivery system.Kavya S
contented and precise , Drug delivery system , sustained release preparation.factors like absorption, distribution ,metabolism , therapeutic window , absorption window.
In recent years many advancement has been made in research and development of Oral Drug Delivery System. Concept of Novel Drug Delivery System arose to overcome the certain aspect related to physicochemical properties of drug molecule and the related formulations.
Purpose of this review is to compile the recent literature with special focus on Gastro Retentive Drug Delivery Systems to give an update
on pharmaceutical approaches used in enhancing the Gastric Residence Time (GRT). Various approaches are currently used including Gastro Retentive Floating Drug Delivery Systems(GRFDDS),swelling and expanding system, polymeric bioadhesive systems, modifiedshape
systems, high density system and other delayed gastric emptying devices. These systems are very helpful to different problem solve during the formulation of different dosage form. The present work also focuses on the polymers used in floating drug delivery systems
mostly from natural origin. Floating drug delivery systems are less dense than gastric fluids; hence remain buoyant in the upper GIT for a
prolonged period, releasing the drug at the desired/ predeterminedrate. This review article focuses on the recent technological development in floating drug delivery systems with special emphasis on the principal mechanism of floatation and advantages of achieving gastric
retention, brief collection on various polymers employed for floating drug delivery systems etc. In addition this review also summarizes the In –Vitro and In -Vivo studies to evaluate their performance and also their future potential.
it provide a brief note on the drug excipient interaction and various technique to find it which is a part of preformulation studies. it gives help to mpharm(pharmaceutics) students. i.
Microemulsion is an isotropic mixture of oil, surfactant, Cosurfactant and drug.
Upon mild agitation followed by dilution in aqueous media, such as gastrointestinal (GI) fluids, the systems can form fine oil in water (O/W) Microemulsions which usually have a droplet size less than 100 nm.
Microemulsion have been successfully used to improve the solubility, chemical stability, and oral bioavailability of many poorly water soluble drugs.
They have characteristic properties such as a low interfacial tension, large interfacial area and capacity to solubilize both aqueous and oil-soluble compounds.
SOLID DISPERSION
Definition: The technology is the science of dispersing one or more active ingredients in an inert matrix in the solid stage.
Need of solid dispersion:
Increases Oral bioavailability of a drug
Increased dissolution rate.
Enhanced release of drugs from ointment.
Improved the solubility & stability.
The concept of solid dispersion was originally proposed by Sekiguchi & obi.
Increasing the dissolution, absorption & therapeutic efficacy of drugs in dosage forms.
Increasing solubility in water.
Improving the oral absorption and bioavailability of BCS Class II drugs.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
Factors affecting sustained release drug delivery system.Kavya S
contented and precise , Drug delivery system , sustained release preparation.factors like absorption, distribution ,metabolism , therapeutic window , absorption window.
In recent years many advancement has been made in research and development of Oral Drug Delivery System. Concept of Novel Drug Delivery System arose to overcome the certain aspect related to physicochemical properties of drug molecule and the related formulations.
Purpose of this review is to compile the recent literature with special focus on Gastro Retentive Drug Delivery Systems to give an update
on pharmaceutical approaches used in enhancing the Gastric Residence Time (GRT). Various approaches are currently used including Gastro Retentive Floating Drug Delivery Systems(GRFDDS),swelling and expanding system, polymeric bioadhesive systems, modifiedshape
systems, high density system and other delayed gastric emptying devices. These systems are very helpful to different problem solve during the formulation of different dosage form. The present work also focuses on the polymers used in floating drug delivery systems
mostly from natural origin. Floating drug delivery systems are less dense than gastric fluids; hence remain buoyant in the upper GIT for a
prolonged period, releasing the drug at the desired/ predeterminedrate. This review article focuses on the recent technological development in floating drug delivery systems with special emphasis on the principal mechanism of floatation and advantages of achieving gastric
retention, brief collection on various polymers employed for floating drug delivery systems etc. In addition this review also summarizes the In –Vitro and In -Vivo studies to evaluate their performance and also their future potential.
it provide a brief note on the drug excipient interaction and various technique to find it which is a part of preformulation studies. it gives help to mpharm(pharmaceutics) students. i.
Microemulsion is an isotropic mixture of oil, surfactant, Cosurfactant and drug.
Upon mild agitation followed by dilution in aqueous media, such as gastrointestinal (GI) fluids, the systems can form fine oil in water (O/W) Microemulsions which usually have a droplet size less than 100 nm.
Microemulsion have been successfully used to improve the solubility, chemical stability, and oral bioavailability of many poorly water soluble drugs.
They have characteristic properties such as a low interfacial tension, large interfacial area and capacity to solubilize both aqueous and oil-soluble compounds.
This will help in find out the difference between micro and nano emulsions. Contain good explanations of their thermdynamic and kinetic stability also ternary phase diagram.
SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEM [SMEDDS]Sagar Savale
Oral route is the main route of drug administration in many diseases. Major problem in oral route of drug administration is bioavailability which mainly results from poor aqueous solubility. This leads to lack of dose uniformity and high intrasubject/intersubject variability. It is found that 40% of active substances are poorly water-soluble. Various technologies are developed to overcome this problem, like solid dispersion or complex formation. Much attention has been given to lipid-based formulation with particular emphasis on self-micro emulsifying drug delivery system to improve the oral bioavailability of lipophilic drugs. It requires small amount of dose and also drugs can be protected from hostile environment in gut. Self-micro emulsifying drug delivery systems are specialized form of delivery system in which drug is encapsulated in a lipid base with or without pharmaceutical acceptable surfactant.
Discussion on the 2 kinds of Disperse Systems 1. Suspensions 2. Emulsions. The principles of emulsification, types and examples of emulsifying agents used.
Microemulsion, Nanoemulsion and Self emulsifying drug delivery systems Pawan Kumar Pandey
Microemulsion, Nanoemulsion and Self emulsifying drug delivery systems and lipidic systems. Difference between emulsions based on the size of the globule. Preparation methods for emulsions used in industry.
Microemulsions are clear, stable and isotropic liquids. It is the mixture of oil, water and surfactant with the use of co surfactants. It acts as a potential drug carrier for parenteral, topical and oral administration. The microemulsion is one of the most used novel drug delivery systems for pharmaceutical applications. They show favorable characteristics such as long shelf life, improved drug solubilization and ease of preparation. Most of the novel vehicles are used for sustained and controlled release systems. They are versatile systems that show a wide range of compounds mainly hydrophobic and hydrophilic domains. They aimed at controlling the bioavailability of the various drug molecules. The review puts forward the recent development of a micro emulsion based system. Manisha Sukre | Sayali Dhepe | Dr. Vijaya Barge "Overview of Microemulsion" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-4 , June 2022, URL: https://www.ijtsrd.com/papers/ijtsrd50106.pdf Paper URL: https://www.ijtsrd.com/pharmacy/pharmaceutics/50106/overview-of-microemulsion/manisha-sukre
“Emulsion of emulsion”, “double or triple emulsion”
Dispersed phase contain smaller droplets that have the same composition as the external phase.
Liquid film which separate the liquid phases acts as a thin semi permeable film through which solute must diffuse in order to travel from one phase to another – “Liquid Membrane System”
Two types: -
Oil-in-water-in-oil (O/W/O) emulsion system.
Water-in-oil-in-water (W/O/W) emulsion system.
SELF-EMULSIFYING DRUG DELIVERY SYSTEM (SEDDS).pptxDipeshGamare
SELF-EMULSIFYING DRUG DELIVERY SYSTEM (SEDDS) is a type of novel drug delivery system, in this presentation all aspect regarding SEDDS are covered with some novel points.
Review on Microemulsion a Novel Approach for Antifungal Drug Deliveryijtsrd
Microemulsion is an best candidates as novel drug drlivery system because of their shelf life and improve the drug solubilization with easy of preparation and administration. The term microemulsion refers to thermodynamically stable iostropically dispersion of two immisible liquid such as oil and water stabilized by interfacial film of surfactant molecule. Now a days microemulsion is an emerging trade and having worldwide importance in varity of technological application .These application include enhanced oil recovery,cosmeceuticals agriculture ,metal cutting,organic and bio organic reaction. Monali B. Lalage | Sujit Kakade | Ashok Bhosale "Review on Microemulsion a Novel Approach for Antifungal Drug Delivery" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-4 | Issue-1 , December 2019, URL: https://www.ijtsrd.com/papers/ijtsrd29759.pdf Paper URL: https://www.ijtsrd.com/pharmacy/pharmaceutics/29759/review-on-microemulsion-a-novel-approach-for-antifungal-drug-delivery/monali-b-lalage
Microemulsion – A Potential Carrier for Improved BioavailabilityBRNSS Publication Hub
Microemulsion (ME) are one of the potential and emerging drug carrier systems that help to improve the drug release and enhance the bioavailability of poorly aqueous soluble drugs. These are considered as thermodynamically stable system which mainly consists of three to five components such as aqueous phase, an oil phase, surfactant, cosurfactant, and in some cases electrolyte. Microemulsion became more popular as a drug delivery system, due to some of its unique features such as its capacity to increase the bioavailability, long shelf life and ease of preparation, and huge scope of application. The delivery system is widely used in different filed such as pharmaceutical, food industries, and cosmetics industries. As per literature, around 40% of the newly arrived drug molecules are poorly water-soluble in nature and results in poor bioavailability. Therefore, ME drug delivery system may play a key role to overcome the mentioned issue. Hence, the review has been written with an aim to address the capacity of ME drug delivery system to overcome the solubility issue of poor water-insoluble drugs and to provide adequate information’s about its possible application.
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2. Microemulsion
• Microemulsions are thermodynamically stable
dispersions of oil and water stabilized by a
surfactant and, in many cases, also a
cosurfactant.
• Microemulsions can have characteristic
properties such as ultralow interfacial tension,
large interfacial area and capacity to solubilize
both aqueous and oil-soluble compounds.
Anand Pharmacy College, ANAND 2
3. “Microemulsions are dispersions of
nanometer-sized droplets of an immiscible
liquid within another liquid. Droplet formation is
facilitated by the addition of surfactants and
often also co surfactants.”
Anand Pharmacy College, ANAND 3
4. Theories of Microemulsion Formation**
• Historically, three approaches have been used to explain microemulsion
formation and stability. They are as follows-
1. Interfacial or mixed film theories.
2. Solubilization theories.
3. Thermodynamic treatments.
• The free energy of microemulsion formation can be considered to depend
on the extent to which surfactant lowers the surface tension of the oil water
interface and change in entropy of the system such that,
Gf = γ a - T S
• Where,
– Gf = free energy of formation
– A = change in interfacial area of microemulsion
– S = change in entropy of the system
– T = temperature
– γ = surface tension of oil water interphase
• It should be noted that when a microemulsion is formed the change in A is
very large due to the large number of very small droplets formed.
• In order for a microemulsion to be formed (transient) negative value of was
required, it is recognized that while value of is positive at all times, it is very
small and it is offset by the entropic component.
Anand Pharmacy College, ANAND 4
5. • The dominant favorable entropic contribution is very large
dispersion entropy arising from the mixing of one phase in
the other in the form of large number of small droplets.
• However there are also expected to be favorable entropic
contributions arising from other dynamic processes such as
surfactant diffusion in the interfacial layer and monomer-
micelle surfactant exchange.
• Thus a negative free energy of formation is achieved when
large reductions in surface tension are accompanied by
significant favorable entropic change.
• In such cases, microemulsion is spontaneous and the
resulting dispersion is thermodynamically stable.
1. Schulman J.H, Stoeckenius, W., Prince, L.M, J. Phys. Chem., 63, 1677-1680. (1959).
Mechanism of formation and structure o f microemulsions by electron Microscopy .
2. Prince L.M, J. Colloid Interface Sci., 23,165-173 (1967). A theory of aqueous emulsions
I.Negative interfacial tension at the oil/water interface
Anand Pharmacy College, ANAND 5
6. Types of microemulsion systems*
• According to Winsor, there are four types of microemulsion phases
exists in equilibria, these phases are referred as Winsor phases
• They are,
Winsor I: With two phases, the lower (o/w)
microemulsion phases in equilibrium with the upper excess oil.
Winsor II: With two phases, the upper (w/o)
microemulsion phase microemulsion phases in equilibrium with lower
excess water.
Winsor III: With three phases, middle
microemulsion phase (o/w plus w/o, called bi continous) in
equilibrium with upper excess oil and lower excess water.
Winsor IV: In single phase, with oil, water and
surfactant homogenously mixed.
*Aboofazeli R, LawrenceM.J, Int. J. Pharm., 93,161-175 (1993). Investigations into the formation and
characterization of phospholipid microemulsions. I. Pseudo-ternary phase diagrams of systems containing
water-lecithin-alcohol-isopropyl myristate.
* Hasse A, Keipert, S, Eur. J. Pharm. Biopharm., 430, 179-183 (1997). Development and characterization of
Anand Pharmacy College, ANAND 6
microemulsions for ocular application.
7. • Advantages Of Microemulsion Over Other Dosage Forms
– Increase the rate of absorption
– Eliminates variability in absorption
– Helps solublize lipophilic drug
– Provides a aqueous dosage form for water insoluble drugs
– Increases bioavailability
– Various routes like tropical, oral and intravenous can be used to
deliver the product
– Rapid and efficient penetration of the drug moiety
– Helpful in taste masking
– Provides protection from hydrolysis and oxidation as drug in oil
phase in O/W microemulsion is not exposed to attack by water
and air.
– Liquid dosage form increases patient compliance.
– Less amount of energy requirement.
Anand Pharmacy College, ANAND 7
8. – Aesthetically appealing products can be formulated as trans-
parent o/w or w/o dispersions called microemulsions.
– These versatile systems are currently of great technological and
scientific interest to the researchers because of their potential to
incorporate a wide range of drug molecules (hydrophilic and
hydrophobic) due to the presence of both lipophilic and hydrophilic
domains.
– These adaptable delivery systems provide protection against
oxidation, enzymatic hydrolysis and improve the solubilization of
lipophilic drugs and hence enhance their bioavailability. In addition
to oral and intravenous delivery, they are amenable for sustained
and targeted delivery through ophthalmic, dental, pulmonary,
vaginal and topical routes.
– Microemulsions are experiencing a very active development as
reflected by the numerous publications and patents being granted
on these systems. Anand Pharmacy College, ANAND 8
9. Component of Microemulsion System
• A large number of oils and surfactant are available but their use in
the microemulsion formulation is restricted due to their toxicity,
irritation potential and unclear mechanism of action.
• Oils and surfactant which will be used for the formulation of
microemulsion should be biocompatible, non-toxic, clinically
acceptable, and use emulsifiers in an appropriate concentration
range that will result in mild and non-aggressive microemulsion.
• The emphasis is, excipients should be generally regarded as safe
(GRAS)[
Anand Pharmacy College, ANAND 9
10. Main three components
1. Oil phase
2. Surfactant
3. Aqueous Component
• If a cosurfactant is used, it may sometimes be represented at a
fixed ratio to surfactant as a single component, and treated as a
single "pseudo-component".
• The relative amounts of these three components can be
represented in a ternary phase diagram.
• Gibbs phase diagrams can be used to show the influence of changes
in the volume fractions of the different phases on the phase
behavior of the system.
Anand Pharmacy College, ANAND 10
11. Oil Component
• The oil component influences curvature by its ability to penetrate and
swell the tail group region of the surfactant monolayer.
• As compare to long chain alkanes, short chain oil penetrate the tail group
region to a greater extent and resulting in increased negative curvature
(and reduced effective HLB).
• Following are the different oil are mainly used for the formulation of
microemulsion:
1. Saturated fatty acid-lauric acid, myristic acid,capric acid
2. Unsaturated fatty acid-oleic acid, linoleic acid,linolenic acid
3. Fatty acid ester-ethyl or methyl esters of lauric, myristic and oleic acid.
• The main criterion for the selection of oil is that the drug should have high
solubility in it.
• This will minimize the volume of the formulation to deliver the therapeutic
dose of the drug in an encapsulated form.
Anand Pharmacy College, ANAND 11
12. Surfactants
• The role of surfactant in the formulation of microemulsion is to lower the
interfacial tension which will ultimately facilitates dispersion process
during the preparation of microemulsion and provide a flexible around the
droplets.
• The surfactant should have appropriate lipophilic character to provide the
correct curvature at the interfacial region.
• Generally, low HLB surfactants are suitable for w/o microemulsion,
whereas high HLB (>12) are suitable for o/w microemulsion.
• Following are the different surfactants are mainly used for microemulsion-
– Polysorbate (Tween 80 and Tween 20), Lauromacrogol 300, Lecithins, Decyl
polyglucoside (Labrafil M 1944 LS), Polyglyceryl-6-dioleate (Plurol Oleique),
Dioctyl sodium sulfosuccinate (Aersol OT), PEG-8 caprylic/capril glyceride
(Labrasol).
Anand Pharmacy College, ANAND 12
13. Co surfactants
• Cosurfactants are mainly used in microemulsion formulation for following
reasons:
• They allow the interfacial film sufficient flexible to take up different
curvatures required to form microemulsion over a wide range of
composition.
1. Short to medium chain length alcohols (C3-C8) reduce the interfacial
tension and increase the fluidity of the interface.
2. Surfactant having HLB greater than 20 often require the presence of
cosurfactant to reduce their effective HLB to a value within the range
required for microemulsion formulation.
• Following are the different cosurfactant mainly used for microemulsion:
– sorbitan monoleate, sorbitan monosterate, propylene glycol, propylene glycol
monocaprylate (Capryol 90), 2-(2-ethoxyethoxy)ethanol (Transcutol) and
ethanol.
Anand Pharmacy College, ANAND 13
14. Preparation of Microemulsion
• Following are the different methods are used
for the preparation of microemulsion*:
1. Phase titration method
2. Phase inversion method
Anand Pharmacy College, ANAND 14
15. Phase titration method
• Microemulsions are prepared by the spontaneous
emulsification method (phase titration method) and can be
portrayed with the help of phase diagram.
• As quaternary phase diagram (four component system) is
time consuming and difficult to interpret, pseudo ternary
phase diagram is constructed to find out the different zones
including microemulsion zone, in which each corner of the
diagram represents 100% of the particular components.
• Pseudo-ternary phase diagrams of oil, water, and co-
surfactant/surfactants mixtures are constructed at fixed
cosurfactant/surfactant weight ratios.
• Phase diagrams are obtained by mixing of the ingredients,
which shall be pre-weighed into glass vials and titrated with
water and stirred well at room temperature. Formation of
monophasic/ biphasic system is confirmed by visual
inspection. Anand Pharmacy College, ANAND 15
17. • In case turbidity appears followed by a phase
separation, the samples shall be considered as
biphasic.
• In case monophasic, clear and transparent
mixtures are visualized after stirring; the
samples shall be marked as points in the
phase diagram.
– The area covered by these points is considered as
the microemulsion region of existence.
Anand Pharmacy College, ANAND 17
18. Phase inversion method
• Phase inversion of microemulsion is carried out upon addition of
excess of the dispersed phase or in response to temperature.
• During phase inversion drastic physical changes occur including
changes in particle size that can ultimately affect drug release
both in vitro and in vivo.
• For non-ionic surfactants, this can be achieved by changing the
temperature of the system,
– forcing a transition from an o/w microemulsion at low temperature
– to -
– a w/o microemulsion at higher temperatures (transitional phase inversion).
Anand Pharmacy College, ANAND 18
19. • During cooling, the system crosses a point zero spontaneous curvature
and minimal surface tension, promoting the formation of finely
dispersed oil droplets.
• Apart from temperature, salt concentration or pH value may also be
considered.
• A transition in the radius of curvature can be obtained by changing the
water volume fraction.
• Initially water droplets are formed in a continuous oil phase by
successively adding water into oil. Increasing the water volume
fraction changes the spontaneous curvature of the surfactant from
initially stabilizing a w/o microemulsion to an o/w microemulsion at
the inversion locus.
Anand Pharmacy College, ANAND 19
20. • Many examples of microemulsion based
formulations are now on the market ;
– Among them, the performances of
microemulsions are well demonstrated in the
reformulation of Cyclosporin A by Novartis into a
microemulsion based formulation marketed under
the trade mark Neoral®
• this has increased the bioavailability nearly by
a factor 2.
Anand Pharmacy College, ANAND 20
21. Characterization Of Microemulsion
1. The droplet size,
2. viscosity,
3. density,
4. turbidity,
5. refractive index,
6. phase separation and
7. pH measurements shall be performed to
characterize the microemulsion.
Anand Pharmacy College, ANAND 21
22. The droplet size
• The droplet size distribution of microemulsion
vesicles can be determined by either light scattering
technique or electron microscopy.
• This technique has been advocated as the best
method for predicting microemulsion stability.
– Dynamic light-scattering measurements.
• The DLS measurements are taken at 90° in a dynamic light-
scattering spectrophotometer which uses a neon laser of
wavelength 632 nm. The data processing is done in the built-in
computer with the instrument.
Anand Pharmacy College, ANAND 22
23. Phase analysis and viscosity measurement
• Polydispersity
– Studied using Abbe refractometer.
• Phase analysis
– To determine the type if microemulsion that has formed the
phase system (o/w or w/o) of the microemulsions is determined
by measuring the electrical conductivity using a conductometer.
• · Viscosity measurement
– The viscosity of microemulsions of several compositions can be
measured at different shear rates at different temperatures
using Brookfield type rotary viscometer.
– The sample room of the instrument must be maintained at 37 ±
0.2°C by a themobath, and the samples for the measurement
are to be immersed in it before testing.
Anand Pharmacy College, ANAND 23
24. In Vitro Drug Permeation Studies
• Determination of permeability coefficient and flux
– Excised human cadaver skin from the abdomen can be obtained from
dead who have undergone postmortem not more than 5 days ago in
the hospital. The skin is stored at 4C and the epidermis separated.
– The skin is first immersed in purified water at 60C for 2 min and the
epidermis then peeled off.
– Dried skin samples can be kept at -20C for later use.
– Alternatively the full thickness dorsal skin of male hairless mice may
be used.
– The skin shall be excised, washed with normal saline and used.
Anand Pharmacy College, ANAND 24
25. – The passive permeability of
lipophilic drug through the skin is
investigated using Franz diffusion
cells with known effective
diffusional area.
– The hydrated skin samples are
used. The receiver compartment
may contain a complexing agent
like cyclodextrin in the receiver
phase, which shall increase the
solubility and allows the
maintenance of sink conditions in
the experiments.
– Samples are withdrawn at regular
interval and analyzed for amount
of drug released.
Anand Pharmacy College, ANAND 25
26. In Vivo Studies
• Bioavailability studies: Skin bioavailability of topical
applied microemulsion on rats
– Male Sprague–Dawley rats (400–500 g), need to be anesthetized
(15 mg/kg pentobarbital sodium i.p.) and placed on their back.
– The hair on abdominal skin shall be trimmed off and then
bathed gently with distilled water.
– Anesthesia should be maintained with 0.1-ml pentobarbital (15
mg/ml) along the experiment.
– Microemulsions must be applied on the skin surface (1.8 cm2)
and glued to the skin by a silicon rubber.
– After 10, 30 and 60 min of in vivo study, the rats shall be killed
by aspiration of ethyl ether.
– The drug exposed skin areas shall be swabbed three to four
times with three layers of gauze pads, then bathed for 30 s with
running water, wiped carefully, tape-stripped (X10 strips) and
harvested from the animals.
Anand Pharmacy College, ANAND 26
27. • Determination of residual drug remaining in
the skin on tropical administration.
– The skin in the above permeation studies can be used to
determine the amount of drug in the skin. The skin
cleaned with gauze soaked in 0.05% solution of sodium
lauryl sulfate and shall bathed with distilled water.
– The permeation area shall be cut and weighed and drug
content can be determined in the clear solution obtained
after extracting with a suitable solvent and centrifuging.
Anand Pharmacy College, ANAND 27
28. • Pharmacological Studies
– Therapeutic effectiveness can be evaluated for the specific
pharmacological action that the drug purports to show as per stated
guidelines.
• Estimation Of Skin Irritancy
– As the formulation is intended for dermal application skin irritancy
should be tested.
– The dorsal area of the trunk is shaved with clippers 24 hours before
the experiment.
– The skin shall be scarred with a lancet. 0.5 ml of product is applied and
then covered with gauze and a polyethylene film and fixed with
hypoallergenic adhesive bandage.
– The test be removed after 24 hours and the exposed skin is graded for
formation of edema and erythema.
– Scoring is repeated a 72 hours later.
– Based on the scoring the formulation shall be graded as
• ‘non-irritant’,
• ‘irritant’ and
• ‘highly irritant’. Anand Pharmacy College, ANAND 28
29. • Stability Studies
– The physical stability of the microemulsion must be
determined under different storage conditions (4, 25 and
40 °C) during 12 months.
– Depending on different regulatory agency requirement it’ll
vary according to them.
– Fresh preparations as well as those that have been kept
under various stress conditions for extended period of
time is subjected to droplet size distribution analysis.
– Effect of surfactant and their concentration on size of
droplet is also be studied.
Anand Pharmacy College, ANAND 29
30. Application of microemulsion in delivery of drug
• Oral delivery
– Microemulsions have the potential to enhance the solubilization
of poorly soluble drugs (particularly BCS class II or class IV) and
overcome the dissolution related bioavailability problems.
– These systems have been protecting the incorporated drugs
against oxidation, enzymatic degradation and enhance
membrane permeability.
– Presently, Sandimmune Neoral(R) (Cyclosporine A),
Fortovase(R) (Saquinavir), Norvir(R) (Ritonavir) etc. are the
commercially available microemulsion formulations.
– Microemulsion formulation can be potentially useful to improve
the oral bioavailability of poorly water soluble drugs by
enhancing their solubility in gastrointestinal fluid.
Anand Pharmacy College, ANAND 30
31. • Parenteral delivery
– The formulation of parenteral dosage form of lipophilic and
hydrophilic drugs has proven to be difficult.
– O/w microemulsions are beneficial in the parenteral delivery of
sparingly soluble drugs where the administration of suspension
is not required.
– They provide a means of obtaining relatively high concentration
of these drugs which usually requires frequent administration.
– Other advantages are that they exhibit a higher physical stability
in plasma than liposome’s or other vehicles and the internal oil
phase is more resistant against drug leaching.
– Several sparingly soluble drugs have been formulated into o/w
microemulsion for parenteral delivery.
Anand Pharmacy College, ANAND 31
32. • Topical delivery
– Topical administration of drugs can have advantages over
other methods for several reasons, one of which is the
avoidance of hepatic first-pass metabolism of the drug and
related toxicity effects.
– Another is the direct delivery and targetability of the drug
to affected areas of the skin or eyes.
– Now a day, there have been a number of studies in the
area of drug penetration into the skin.
– They are able to incorporate both hydrophilic (5-
flurouracil, apomorphine hydrochloride, diphenhydramine
hydrochloride, tetracaine hydrochloride, methotrexate)
and lipophilic drugs (estradiol, finasteride, ketoprofen,
meloxicam, felodipine, triptolide) and enhance their
permeation.
Anand Pharmacy College, ANAND 32
33. • Ophthalmic delivery
– Low corneal bioavailability and lack of efficiency in the posterior
segment of ocular tissue are some of the serious problem of
conventional systems.
– Recent research has been focused on the development of new
and more effective delivery systems.
– Microemulsions have emerged as a promising dosage form for
ocular use.
– Chloramphenicol, an antibiotic used in the treatment of
trachoma and keratitis, in the common eye drops hydrolyzes
easily.
– Fialho et al. studied microemulsion based dexamethasone eye
drops which showed better tolerability and higher
bioavailability. The formulation showed greater penetration in
the eye which allowed the possibility of decreasing dosing
frequency and thereby improve patient compliance.
Anand Pharmacy College, ANAND 33
34. • Nasal delivery
– Recently, microemulsions are being studied as a delivery system
to enhance uptake of drug through nasal mucosa.
– In addition with mucoadhesive polymer helps in prolonging
residence time on the mucosa.
– Lianly et al. investigated the effect of diazepam on the
emergency treatment of status epilepticus.
– They found that the nasal absorption of diazepam fairly rapid at
2 mg kg-1 dose with maximum drug plasma concentration
reached within 2-3 min
Anand Pharmacy College, ANAND 34
35. • Drug targeting
– Drug targeting to the different tissues has evolved asthe most
desirable goal of drug delivery.
– By altering pharmacokinetics and biodistribution of drugs and
restricting their action to the targeted tissue increased drug
efficacy with concomitant reduction of their toxic effects can be
achieved.
– Shiokawa et al. reported a novel microemulsion formulation for
tumor targeting of lipophilic antitumor antibiotic aclainomycin A
(ACM).
– They reported that a folate-linked microemulsion is feasible for
tumour targeted ACM delivery.
– They also reported that folate modification with a sufficiently
long PEG chain on emulsions is an effective way of targeting
emulsion to tumour cells.
Anand Pharmacy College, ANAND 35
37. • SEDDSs are isotropic mixtures of oils and surfactants,
sometimes containing cosolvents, and can be used for the
design of formulations in order to improve the oral absorption
of highly lipophilic compounds.
• SEDDSs emulsify spontaneously to produce fine oil-in-water
emulsions when introduced into an aqueous phase under
gentle agitation.
• SEDDS can be orally administered in soft or hard gelatine
capsules and form fine, relatively stable oil-in-water
emulsions upon aqueous dilution.
Anand Pharmacy College, ANAND 37
38. • Self-emulsifying formulations spread readily in the
gastrointestinal (GI) tract, and the digestive motility of
the stomach and the intestine provide the agitation
necessary for selfemulsification.
• These systems advantageously present the drug in
dissolved form and the small droplet size provides a
large interfacial area for the drug absorption.
• SEDDSs typically produce emulsions with a droplet size
between 100–300 nm while self-microemulsifying drug
delivery systems (SMEDDSs) form transparent
microemulsions with a droplet size of less than 50 nm.
Anand Pharmacy College, ANAND 38
39. • Composition of SEDDSs
– The self-emulsifying process is depends on:
• The nature of the oil–surfactant pair
• The surfactant concentration
• The temperature at which self-emulsification occurs.
Anand Pharmacy College, ANAND 39
40. • 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.
– Long-chain triglyceride and medium-chain triglyceride
oils
– Modified or hydrolyzed vegetable oils have
contributed widely to the success of SEDDSs owing to
their formulation and physiological advantages
Anand Pharmacy College, ANAND 40
41. • Surfactant
– Nonionic surfactants with high hydrophilic–
lipophilic balance (HLB) values are used in
formulation of SEDDSs (e.g., Tween, Labrasol,
Labrafac CM 10, Cremophore, etc.).
– The usual surfactant strength ranges between 30–
60% w/w of the formulation in order to form a
stable SEDDS.
Anand Pharmacy College, ANAND 41
42. • Cosolvents
– Cosolvents like diehylene glycol monoethyle ether
(transcutol), propylene glycol, polyethylene glycol,
polyoxyethylene, propylene carbonate,
tetrahydrofurfuryl alcohol polyethylene glycol
ether (Glycofurol), etc., 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.
Anand Pharmacy College, ANAND 42
43. 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.
– The preparation of SEDDS formulation by
dissolving the drug in a mix of oil, surfactant and
cosolvent.
Anand Pharmacy College, ANAND 43
44. • The addition of a drug to a SEDDS is critical
because the drug interferes with the self-
emulsification process to a certain extent, which
leads to a change in the optimal oil–surfactant
ratio.
• So, the design of an optimal SEDDS requires
preformulation-solubility and phase-diagram
studies. In the case of prolonged SEDDS,
formulation is made by adding the polymer or
gelling agent
Anand Pharmacy College, ANAND 44
45. Mechanism of self-emulsification
• According to Reiss, self-emulsification occurs
when the entropy change that favors
dispersion is greater than the energy required
to increase the surface area of the dispersion.
Where,
DG is the free energy associated with the process
N is the number of droplets
R is radius of droplet
S is interfacial tension
Anand Pharmacy College, ANAND 45
46. Characterization of SEDDSs
• The primary means of self-emulsification assessment is visual
evaluation. The efficiency of self-emulsification could be
estimated by determining the rate of emulsification, droplet-
size distribution and turbidity measurements.
• 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.
Anand Pharmacy College, ANAND 46
47. • 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
Nano sizer 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, isotropic 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 and scored according to techniques described in H. Shen et al.
used for the grading of Anand Pharmacy College, ANAND
formulations. 47