This document discusses transdermal drug delivery and penetration enhancement techniques. It begins with an introduction to transdermal drug delivery and the barriers of the skin. It then discusses various penetration enhancement techniques including chemical agents, physical methods, vesicles and prodrugs. Specific penetration enhancers are explained such as surfactants, fatty acids, DMSO, alcohols and terpenes. The mechanisms of these enhancers are also summarized. The document concludes with a discussion of other approaches like supersaturated solutions, eutectic mixtures, complexes, microneedles and iontophoresis. Overall, the document provides an overview of strategies to enhance drug permeation across the skin for transdermal drug delivery.
This slide share includes the introduction about smedds, difference between emulsion and smedd and sedds and smedds, composition and its formulation aspects.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
Penetration Enhancers in Transdermal Drug Delivery SystemSimranDhiman12
Penetration Enhancers in Transdermal Drug Delivery System
Permeation enhancers are substances that reduce the skin barrier's ability to make skin more permeable and allow drug molecules to cross the skin at a faster rate
advantages and disadvantages
types of penetration enhancers
techniques
physical and chemical enhancers
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.
Transdermal Drug Delivery System [TDDS]Sagar Savale
Management of illness through medication has entered an era of rapid growth. A variety of means by which drugs are delivered to the human body for the therapy such as tablets, capsules, injections, aerosols, creams, ointments, suppositories, liquids etc. are referred as a conventional drug formulations. Among many pharmaceutical dosage forms, continuous intravenous infusion at preprogrammed rate has been recognized as a superior mode of drug delivery. At present, the most common form of delivery of drugs is the oral route. It has the notable advantage of easy administration.
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
This slide share includes the introduction about smedds, difference between emulsion and smedd and sedds and smedds, composition and its formulation aspects.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
Penetration Enhancers in Transdermal Drug Delivery SystemSimranDhiman12
Penetration Enhancers in Transdermal Drug Delivery System
Permeation enhancers are substances that reduce the skin barrier's ability to make skin more permeable and allow drug molecules to cross the skin at a faster rate
advantages and disadvantages
types of penetration enhancers
techniques
physical and chemical enhancers
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.
Transdermal Drug Delivery System [TDDS]Sagar Savale
Management of illness through medication has entered an era of rapid growth. A variety of means by which drugs are delivered to the human body for the therapy such as tablets, capsules, injections, aerosols, creams, ointments, suppositories, liquids etc. are referred as a conventional drug formulations. Among many pharmaceutical dosage forms, continuous intravenous infusion at preprogrammed rate has been recognized as a superior mode of drug delivery. At present, the most common form of delivery of drugs is the oral route. It has the notable advantage of easy administration.
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
Glass as a packaging material in pharmaceutical packagingShweta Shelke
This presentation gives a brief idea about the types of glasses used in pharmaceutical industry and its intended use. Different tests used for assuring its quality for intended use.
FORMULATION AND EVALUATION OF OCUSERTS OF CIPROFLOXACIN HClMohammad Adil
Conventional ocular drug delivery system i.e., eye drops, ointments, gels etc., had become less popular pertaining to their disadvantages like evaporation by tears, pre-corneal loss, drug metabolism, drug-protein interaction, drainage, sticking of eye lids, induced lacrimation, poor patient compliance, systemic side effect and blurred vision etc. That’s why fundamentals of controlled release by means of ocular inserts were utilized to increase problem pre-corneal drug residence time.
This project title “Formulation and Evaluation of Ocuserts of Ciprofloxacin HCl” revealed following results:
Compatibility study using FTIR was performed to check the compatibility of drug with various excipient. Characteristics peaks obtained with pure drug were compared with that produced with different excipients that confirmed the compatibility of drug with excipients.
Ocusert of Ciprofloxacin HCl was prepared using different material i.e., PVP K-30, PVA, PEG 400 and glycerin.
Prepared ocuserts were evaluated for various parameters viz., percentage moisture loss, percentage moisture absorbs, thickness, weight variation, drug content and In-vitro diffusion.
The percentage (%) moisture absorption and loss of ocular insert were found to be 26% and 27% respectively.
The thickness of ocular insert was found to be uniformed and its mean while measuring at different points was found to be 0.124mm.
The weight of ocular inserts was found to be in the range of 12.2 - 12.6mg which indicated decent distribution of the drug, polymer and plasticizer.
The drug content of ocular insert was found to be 99.89%.
Percentage drug release from Ciprofloxacin HCl Ocusert was found to be 41.969% in 8 hr.
It was concluded that prepared Ocusert of Ciprofloxacin HCl could be a better alternative to conventional ocular formulations that retained on ocular surface for longer duration and released drug in controlled manner.
Its not as good but still comprises outlines for added substances of parenteral in good.
All credit goes to Mr. Saifullah Khan.
Leave your comments to let us improve it for more.
Skin acts as a major target as well as a principal barrier for topical/transdermal drug delivery. Despite the many advantages of this system, the major obstacle is the low diffusion rate of drugs across the stratum corneum. Several methods have been tried to increase the permeation rate of drugs temporarily. One simple and convenient approach is application of drugs in formulation with elastic vesicles or skin enhancers. Vesicular system is one of the most convenient methods for transdermal delivery of active substances and in that ethosomes are most useful vesicular systems. Ethosomal carriers are systems containing soft vesicles, composed of hydroalcoholic or hydro/glycolic phospholipid in which the concentration of alcohols is relatively high. The high concentration of ethanol brings increase in fluidity of lipids hence increase in permeability of the skin and improves the drug penetration. Ethosomal formulation may contain many drugs such as acyclovir, salbutamol, Insulin, cyclosporine, fluconazole, minodixil, etc. These are prepared by hot method and cold methods. The size of Ethosomal formulation can be decreased by sonication and extrusion method. The high concentration of ethanol makes the ethosomes unique and useful for transcellular delivery, delivery of hormones, anti-arthritis, anti-HIV etc. Thus, it can be a logical conclusion that ethosomal formulation possesses promising future in effective dermal/transdermal delivery of bioactive agents.
Introduction and classification, anatomy of skin and factors affecting absorption, Formulation ,preparation, packaging, labeling and storage of ointments, Formulation, preparation, packaging, labeling and storage of jellies, creams, pastes.
Semisolid dosage forms: Definitions, classification, mechanisms and factors influencing dermal penetration of drugs. Preparation of ointments, pastes, creams and gels. Excipients used in semi solid dosage forms. Evaluation of semi solid dosages forms
1)Introduction
2)Advantages and Disadvantages
3)Structure of Skin
4)Permeation through skin
5)Factors affecting permeation
6)Basic Componentes of TDDS
7)Formulation approaches used in the development of TDDS
8)Evaluation of TDDS
9)Reference
Formulation and evaluation of antifungal ketoconazole emulgelShwetaKate3
Formulation and evaluation of ketoconazole Emulgel:Controlled drug delivery ,
Presentation by Gajanan S. Lahade
M.pharm second year,
PDEA'S Seth govind raghunath Sable college of pharmacy, saswad ,pune,India
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
The Art Pastor's Guide to Sabbath | Steve ThomasonSteve Thomason
What is the purpose of the Sabbath Law in the Torah. It is interesting to compare how the context of the law shifts from Exodus to Deuteronomy. Who gets to rest, and why?
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
How to Split Bills in the Odoo 17 POS ModuleCeline George
Bills have a main role in point of sale procedure. It will help to track sales, handling payments and giving receipts to customers. Bill splitting also has an important role in POS. For example, If some friends come together for dinner and if they want to divide the bill then it is possible by POS bill splitting. This slide will show how to split bills in odoo 17 POS.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
Instructions for Submissions thorugh G- Classroom.pptx
Permeation enhancement through skin
1. Presented by Guided by
Mr.Thakur Rohit.G Dr.Kokare C.R.
Sem-II(Pharmaceutics)
4/27/2012 1
2. Introduction Transdermal DDS Structure of Skin Transport across Skin
Barriers Factors Penetration enhancement References
4/27/2012 2
3. The aim of drug administration via skin can be either the local therapy or
the transdermal drug delivery to the systemic circulation.
Skin presents number of barriers for transport of drug through it.
To enhance the transport of the drug through the skin various techniques
are applied called as penetration enhancement techniques and the agents
utilized in it are “PENETRATION ENHANCERS”.
4/27/2012 3
4. Benefits of i.v. infusion can be closely duplicated without its
hassles by using skin as the port of entry of drugs.
Adverse effects or therapeutic failures frequently associated
with intermittent dosing can also be avoided.
Improved patient compliance.
Self administrable & drug input can be terminated at any
point of time.
4/27/2012 4
9. Stratum Corneum
High density of skin
Low hydration of skin
Low area for solute transport (Because most
solute enter through the 0.1 micron
intercellular space.
4/27/2012 9
10. Diffusion through stratum corneum
Solubility in the stratum corneum
Partitioning
Conditions of the skin
Effect of moisture
Effect of vehicles
Effect of concentration of medicament
Effect of surfactants
4/27/2012 10
11. Skin penetration enhancement techniques have been
developed to improve bioavailability and increase the range of
drugs for topical and transdermal delivery.
Penetration enhancers (sorption promoters or accelerants)
which penetrate into skin to decrease the barrier resistance.
Alternatively, physical mechanism such as iontophoresis and
sonophoresis can be used for certain cases of drugs.
4/27/2012 11
12. Chemical Physical Vesicles
Prodrugs Iontophoresis Liposomes
Sonophoresis Transferosomes
Chemical Ethosomes
agents Magnetophoresis SLN
Ion pairs Electroporation
Microneedles
Supersaturated
solutions
Needle-free
injection
Complexes
Photomechanical
Waves
Eutectic
Systems Laser assisted
4/27/2012 12
13. Chemical enhancers or penetration enhancers or absorption
promoters are the agents that interact with skin constituents to
promote the drug flux.
Many agents have been studied & evaluated for enhancement
properties.
Yet their inclusion in skin formulation is limited due to
unknown mechanism & toxicity.
4/27/2012 13
14. Non toxic, non
irritating, non
allergic
Compatible with
Ideally work
both excipients &
drug rapidly
Ideal
Cosmetically Penetration
Pharmacologically
acceptable. Enhancers inert.
Skin barrier Predictable &
properties should reproducible
return both rapidly duration of
& fully. action.
Should work
unidirectionally.
4/27/2012 14
15. 1. By increasing the diffusion coefficient of the drug.
2. By increasing the effective concentration of the drug in the
vehicle.
3. By improving partitioning between the formulation and the
stratum corneum.
4. By decreasing the skin thickness.
4/27/2012 15
16. Fig-5 Mode of action of penetration enhancers
4/27/2012 16
17. 1. Surfactants :
a) Ionic: SLS, Na laurate, etc.
b) Non ionic : Tween 80, Polysorbates, etc.
2. Bile Salts & Derivatives :
e.g.. Na glycocholate, Na deoxycholate
3. Fatty Acid & Derivatives :
e.g.. Oleic acid, Caprylic acid, etc.
4. Chelating Agents :
e.g.. EDTA, Citric acid, etc.
4/27/2012 17
18. 5. Sulphoxide :
e.g.. DMSO, DMA, DMF, etc.
6. Polyols :
e.g. : PG, PEG, Glycerol, etc.
7. Monohydric Alcohols :
e.g. : Ethanol, 2- Propanol, etc.
8. Miscellaneous :
e.g. : a) Urea & its derivatives
b) Terpenes & Terpenoids
c) Phospholipids
d) Water
e)Azones
4/27/2012 18
19. The water content of human stratum corneum is typically
around 15-20% of tissue dry weight.
Soaking the skin in water, exposing the membrane to high
humidities or, occluding allow the stratum corneum to reach
water contents in equilibrium with underlying epidermal skin
cells.
Water content increases to 400%.
In general, increased tissue hydration appears to increase
transdermal delivery of both hydrophilic & lipophilic permeants
4/27/2012 19
20. Water present in stratum corneum is in two form, bound & free,
Free form act as solvent for polar permeants to diffuse.
MOA:
Free water act as solvent & alter solubility of permeants & so
its partitioning.
The corneocytes take up water and swell, such swelling of cells
would impact upon the lipid structure between the corneocytes
causing some disruption to the bilayer packing.
4/27/2012 20
21. Are made up of alkyl or aryl side chain with polar head group.
Have potential to damage human skin.
Both anionic & cationic surfactant can be used, but non ionic
surfactant are safe.
Non ionic – minor effect, anionic – pronounced effect.
MOA:
Solubilise the lipophilic active ingredient & also have potential
to solubilise lipids within the stratum corneum.
4/27/2012 21
22. Oleic acid & other long chain fatty acid are used.
Effective at low concentration(<10%)
Used both for hydrophilic & lipophilic drugs.
Saturated alkyl chain lengths of around C10–C12 attached to a polar head
group yields a potent enhancer.
In unsaturated compounds, the bent cis configuration is expected to disturb
intercellular lipid packing more than trans.
Used for estradiol, acyclovir, 5 FU, Salicylic acid.
MOA:
Interacts with & modifies the lipid domains of stratum corneum discrete
lipid domains are induced within stratum corneum bilayer lipid on exposure
to oleic acid.
4/27/2012 22
23. Dimethyl sulphoxide(DMSO), aprotic solvent which form
hydrogen bond with itself rather than with water.
Used in many areas of pharmaceutical sciences as a „„universal
solvent‟‟.
Promotes both hydrophilic & hydrophobic permeants.
Effect is concentration dependent(> 60% needed for optimum
action).
At high concentration – erythema & wheal, may denature
proteins.
Metabolite dimethyl sulfide produces foul odor on breath.
4/27/2012 23
24. To avoid above side effects researchers have investigated
chemically related materials – DMAC & DMF.
MOA:
Denature protein, changes the keratin confirmation from α
helical to β – sheet.
Interacts with the head groups of some bilayer lipids to
distort to the packing geometry.
Also may facilitate drug partitioning from formulation to this
universal solvent.
4/27/2012 24
25. Ethanol is used most commonly in patches.
Used for levonorgestrol, estradiol, 5 FU, etc.
Its effect is concentration dependent, at high concentration causes
dehydration of biological membrane & decreases the permeation.
Applied in concentration range from 1 – 10%.
Branched alkanols show lower activity.
1- Butanol most effective.
1-octanol and 1-propranolol to be effective enhancers for salicylic
acid and nicotinamide.
4/27/2012 25
26. MOA:
Act as solvent.
Alter solubility property of tissue leads to improvement in drug
partitioning.
Volatile nature of ethanol help in modifying thermodynamic
activity of drug.
Due to evaporation of ethanol drug concentration increases
providing supersaturated state with greater driving force.
Solvent drag may carry permeant into the tissue.
As volatile solvent may extract lipid fraction from skin.
4/27/2012 26
27. Hydrating agent, have been used in scaling conditions such as
psoriasis & other skin conditions.
It produces significant stratum corneum hydration, produces
hydrophilic diffusion channels.
Has keratolytic properties, usually when used in combination with
salicylic acid for keratolysis.
Urea itself possesses only marginal penetration enhancing activity.
Cyclic urea analogues and found them to be as potent as Azone for
promoting indomethacin.
4/27/2012 27
28. Used as medicines, flavoring and fragrance agents.
Hydrocarbon terpenes are less potent, alcohol/ ketone containing terpenes moderate
and oxide & terpenoid shows greatest enhancement .
Smaller terpenes are more active than larger.
Non polar(limonene) agents active for lipophilic drugs & polar(menthol) for
hydrophilic drugs.
MOA:
Modify the solvent nature of the stratum corneum, improving drug partitioning.
Alters thermodynamic activity of the permeant.
Terpenes may also modify drug diffusivity through the membrane.
4/27/2012 28
29. Generally employed as vesicles (liposomes) to carry drugs.
In a non-vesicular form as penetration enhancers.
Phosphatidylcholine & hydrogenated soya bean phospholipids have been
reported to enhance penetration of theophylline & diclofenac respectively.
MOA:
Occlude the skin surface & thus increase tissue hydration.
Phospholipids fuse with stratum corneum lipids.
This collapse of structure liberates permeant into the vehicle where drug is
poorly soluble and hence thermodynamic activity could be raised so
facilitating drug delivery.
4/27/2012 29
30. First chemically design molecule as penetration enhancer.
Promote flux both hydrophilic & lipophilic permeants.
Highly lipophilic with Log o/w =6.2.
Effective at low concentration(0.1 – 5%).
Soluble in & compatible with most organic solvents.
Enhances permeation of steroids, antiviral & antibiotics.
MOA:
Interact with the lipid domains of the stratum corneum.
Partition into the lipid bilayer to disrupt their packing arrangement.
4/27/2012 30
31. Mostly used member : 2- Pyrrolidone(2P) & N- Methyl -2- Pyrrolidone(NMP).
NMP & 2P are miscible with most organic solvents.
Used for numerous molecules including hydrophilic (e.g. mannitol, & 5-FU) and
lipophilic ( hydrocortisone and progesterone) permeants.
Greater effect on hydrophilic drugs.
MOA:
May act by altering the solvent nature of the membrane and pyrrolidones have been
used to generate „reservoirs‟ within skin membranes.
Such a reservoir effect offers potential for sustained release of a permeant.
4/27/2012 31
32. It is difficult to select rationally a penetration enhancer for a
given permeant.
Penetration enhancers tend to work well with co-solvents such
as PG or ethanol.
Most penetration enhancers have a complex concentration
dependent effect.
Permeation through animal skins & rodent skins are generally
considerably greater than those obtained with human skin.
4/27/2012 32
33. Drugs with unfavourable partition coefficients.
Prodrug approach increases the partition coefficient, hence solubility
and transport.
Esterases in viable epidermis releases the moiety from Prodrug,
e.g.. 5-flurouacil solubility increases 25 times by use of N-acyl
derivative.
Very polar 6-mercaptopurine was increased up to 240 times using 6-
acyloxymethyl and 9 dialkylaminomethyl promoieties.
Lipophilic ion pair concept. eg. Ibuprofen ion pair.
4/27/2012 33
34. Supersaturated solution of drug, where high thermodynamic
activity and high penetration power.
Supersaturated solutions obtained due to evaporation of
solvent or by mixing of cosolvents.
Water is imbibed from the skin in to vehicle, thermodynamic
activity of the permeant would increase.
Increase in the flux of estradiol about 10 to 15 times have
been reported.
4/27/2012 34
35. The melting point of a drug delivery system can be lowered by formation
of a eutectic mixture, a mixture of two components which, at a certain ratio,
inhibit the crystalline process of each other.
The melting point of a drug influences solubility and hence skin
penetration.
A good eg. is cream formulation of lignocaine and prilocaine applied
under an occlusive film.
A number of eutectic systems containing a penetration enhancer as the
second component have been reported, for example: ibuprofen with
terpenes , menthol and methyl nicotinate ; propranolol with fatty acids
4/27/2012 35
36. COMPLEXES
Cyclodextrin complexes enhance aqueous solubility and drug stability.
The CDs are relatively large molecules, and consequently both they and
their complexes are not able to permeate through intact skin easily.
Lipophilic CDs (as DM-β-CD and RM-β-CD) are absorbed to a greater
extent.
Enhance the drug thermodynamic activity.
The enhancement of drug release from vehicles by improving the drug
availability at the lipophilic absorptive barrier surface (i.e. Skin).
4/27/2012 36
38. MICRONEEDLES
Needles with or without hollow centre channels are placed on to the skin
surface so that they penetrate the SC and the epidermis without reaching
the nerve endings present in the upper epidermis
Fig- 6 Microneedles
4/27/2012 38
39. Principle: A current passed between the active electrode and the
LidositeTM
indifferent electrode repelling drug away from the active electrode
Fig-7 Iontophoresis and into the skin. E-TRANS – In Phase III
4/27/2012 39
40. Skin electroporation (electropermeabilization) creates transient
aqueous pores in the lipid by application of high voltage of
electric pulses of approximately of 100 to 1000V/cm for short
time(milliseconds).These pores provide pathways for drug
penetration that travel straight to the horny layer.
This technology has been used successfully to enhance the skin
permeability of molecules with varying lipophilicity and size
including biopharmaceuticals with molecular weights greater than
7kDA.
4/27/2012 40
42. Ultrasound pulses are passed through the probe into the skin
fluidizing the lipid bilayers by the formation of bubbles caused by
Fig-9 Sonophoresis
4/27/2012
cavitation 42
43. Also known as laser generated stress waves.
There is pressure pulse generated by ablation of target material
(polystyrene), MOA is unclear but it is believed that it leads to change in
the lacunar system within stratum corneum.
Experimental study on rats shows that reductions in blood glucose of
around 80 3%, and was maintained below 200mg/dl for more than 3 hr.
Hand held portable laser device.( Norrwood abbey ltd. Australia) of local
anesthetic lidocaine.
Not much of attention is paid on this technique, as it is new and due to
lack of clinical data.
4/27/2012 43
45. Enhancement of skin permeability by applying a magnetic
field to therapeutic molecules that are dimagnetic or
paramagnetic.
LEDDTTM
Fig-11 Laser Assisted Penetration
4/27/2012 45
47. Liposome-
Liposomes are colloidal particles formed as concentric bimolecular layers
that are capable of encapsulating drugs.
Amphiphilic, higher diffusivity, high biocompatibility, longer release
time, greater stability, improved penetration and controlled degradation.
MOA-
Phospholipids in liposomal systems can disrupt the bilayer fluidity in the
SC.
Used for high molecular weight and low solubility drug.
Creating a lipid-enriched environment.
4/27/2012 47
48. Ethosomes- (“soft vesicles”)
Ethosomes are soft, malleable vesicles composed mainly of phospholipids, ethanol
(relatively high concentration) and water.
Ethosomes improving the drug's efficacy, enhancing patient compliance and
comfort and reducing the total cost of treatment.
MOA-
Ethanol effect- ethanol disturbance of skin lipid bilayer, partial extraction of SC
lipids and decreases density.
Due to ethanol concentration, the lipid membrane is packed less tightly than
conventional vesicles, improves drug distribution.
e.g. Testosom patch
4/27/2012 48
49. Transfersomes-
These are specially designed lipid surfactant vesicles
for transdermal or topical delivery of bioactive molecules.
Phospholipids, 10-25% surfactant, and 3-10% ethanol.
Ultra deformable carrier system.
4/27/2012 49
50. SALIENT FEATURES
High Deformability
High Penetration Ability Across the Skin
High Entrapment Efficiency
Suitable for Both High As Well As Low Molecular Weight
drugs
4/27/2012 50
51. Solid lipid nanoparticles-
Spherical, with average diameters between 50 to 500nm, Solid
lipid nanoparticles possess a solid lipid core matrix that can
solubilize lipophilic molecules.
4/27/2012 Fig-13 Solid Lipid Nanoparticles 51
52. Melting point must exceed body temperature.
Triacylglycerols (triglycerides), acylglycerols, fatty acids,
steroids, waxes.
Surfactants include lecithin, bile salts such as sodium
taurocholate, biocompatible nonionics such as ethylene
oxide/propylene oxide copolymers, sorbitan esters.
4/27/2012 52
53. MOA-
Occlusion can enhance the penetration of drugs through the stratum
corneum by increased hydration.
Due to hydration pore size will increase.
Nanoparticles have high adhesion to the stratum corneum due to their
small particle size.
SLN of Vitamin A in gel.
TransoPlex®, AlphaRx(USA) is developing Vancomycin - Vansolin™ and
Gentamycin -Zysolin™ trade names
4/27/2012 53
54. Williams A.C, Barry B.W,2004. Penetration enhancers. Adv. Drug Deliv Rev. 56, 603-
618.
Pathan I.B, Setty C.M,2009. Chemical Penetration Enhancers for Transdermal Drug
Delivery Systems. Tropical Journal of Pharmaceutical Research. 8, 173-179.
Baheti S.R et al., 2011. A recent approach towards Transdermal Drug delivery by
Physical and Chemical Techniques. Internationale Pharmaceutica Sciencia. 1, 42-53.
Yiping Wang et al., 2005. Transdermal iontophoresis:combination strategies to improve
transdermal iontophoretic drug delivery. Eur. J. Pharmaceut Biopharmaceut. 60, 179-191
Dhamecha D.L et al., 2009. Drug vehicle based approaches of penetration enhancement.
International Journal of Pharmacy and Pharmaceutical Sciences. 1, 24-46.
Subramony A.J et al.,2006. Microprocessor controlled transdermal drug delivery. Int. J.
Pharm. 317, 1-6.
4/27/2012 54
55. Barry B.W.,2001. Novel mechanisms and devices to enable successful transdermal drug
delivery. Eur. J. Pharm. Sci. 14, 101-114.
L Machet, A. Boucaud,2002. Phonophoresis: efficiency, mechanisms and skin tolerance. Int.
J. Pharm. 243, 1-15
Remington,2006. The Science & Practice of Pharmacy,Twenty-oneth ed. Vol.
2, Lippincott, Williams & Wilkins, pp. 959.
Jain N.K.,1997. Controlled and Novel Drug delivery, First ed. CBS Publishers &
Distributors, pp.100.
4/27/2012 55