Gastro retentive drug delivery system (GRDDS)Shweta Nehate
Oral route is the most acceptable route for drug administration. Apart from conventional dosage forms several other forms were developed in order to enhance the drug delivery for prolonged time period and for delivering drug to a particular target site. Gastro-retentive drug delivery system (GRDDS) has gainned immense popularity in the field of oral drug delivery recently. it is a widely employed approach to retain the dosage form in the stomach for an extended period of time and release the drug slowly that can address many challenges associated with conventional oral delivery, including poor bioavailability. different innovative approaches are being applied to fabricate GRDDS. Gastroretentive drug delivery is an approach to prolong gastric residence time, there by targeting site-specific drugs release in the upper gastrointestinal tract (GIT) for local or systemic effects. It is obtained by retaining dosage form into stomach and by releasing the in controlled manner.
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
Gastro retentive drug delivery system (GRDDS)Shweta Nehate
Oral route is the most acceptable route for drug administration. Apart from conventional dosage forms several other forms were developed in order to enhance the drug delivery for prolonged time period and for delivering drug to a particular target site. Gastro-retentive drug delivery system (GRDDS) has gainned immense popularity in the field of oral drug delivery recently. it is a widely employed approach to retain the dosage form in the stomach for an extended period of time and release the drug slowly that can address many challenges associated with conventional oral delivery, including poor bioavailability. different innovative approaches are being applied to fabricate GRDDS. Gastroretentive drug delivery is an approach to prolong gastric residence time, there by targeting site-specific drugs release in the upper gastrointestinal tract (GIT) for local or systemic effects. It is obtained by retaining dosage form into stomach and by releasing the in controlled manner.
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
Transdermal Drug Delivery System (TDDS) is the one of the novel technology to deliver the molecules through the skin for long period of time.
Transdermal Drug Delivery System (TDDS) are defined as self contained, discrete dosage forms which are also known as “patches” 2, 3 when patches are applied to the intact skin, deliver the drug through the skin at a controlled rate to the systemic circulation
Video Lecture is available at https://www.youtube.com/watch?v=DXu_CLgB4q0
Introduction, terminology/definitions and rationale, advantages, disadvantages, selection of drug candidates. Approaches to design-controlled release formulations based on diffusion, dissolution and ion exchange principles. Physicochemical and
biological properties of drugs relevant to controlled release formulations.
Approaches Of Gastro-Retentive Drug Delivery System or GRDDSAkshayPatane
Approaches Of Gastro-Retentive Drug Delivery System
Includes:
Floating and Non-Floating drug delivery system with their subtypes
Like Non-effervescent system, Effervescent system, Raft forming system,
High Density system, Expandable system, Muco-adhesive system,
Super porous hydrogel system and Magnetic Systems, etc.
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
Transdermal Drug Delivery System (TDDS) is the one of the novel technology to deliver the molecules through the skin for long period of time.
Transdermal Drug Delivery System (TDDS) are defined as self contained, discrete dosage forms which are also known as “patches” 2, 3 when patches are applied to the intact skin, deliver the drug through the skin at a controlled rate to the systemic circulation
Video Lecture is available at https://www.youtube.com/watch?v=DXu_CLgB4q0
Introduction, terminology/definitions and rationale, advantages, disadvantages, selection of drug candidates. Approaches to design-controlled release formulations based on diffusion, dissolution and ion exchange principles. Physicochemical and
biological properties of drugs relevant to controlled release formulations.
Approaches Of Gastro-Retentive Drug Delivery System or GRDDSAkshayPatane
Approaches Of Gastro-Retentive Drug Delivery System
Includes:
Floating and Non-Floating drug delivery system with their subtypes
Like Non-effervescent system, Effervescent system, Raft forming system,
High Density system, Expandable system, Muco-adhesive system,
Super porous hydrogel system and Magnetic Systems, etc.
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
Penetration enhancers are used to increase the penetration of the drug into the body through the skin and mucus also. These enhancers having different category having special effect on the mucus and skin as well. In this presentation enlighten those points of penetration enhancers which are related to the mucoadhesive drug delivery system. this presentation covers types of penetration enhancers, their mechanism of action, route of penetration and their examples.
Accurately answering verbose queries that describe a clinical case and aim at finding articles in a collection of medical literature requires capturing many explicit and latent aspects of complex information needs underlying such queries. Proper representation of these aspects often requires query analysis to identify the most important query concepts as well as query transformation by adding new concepts to a query, which can be extracted from the top retrieved documents or medical knowledge bases. Traditionally, query analysis and expansion have been done separately. In this paper, we propose a method for representing verbose domain-specific queries based on weighted unigram, bigram, and multi-term concepts in the query itself, as well as extracted from the top retrieved documents and external knowledge bases. We also propose a graduated non-convexity optimization framework, which allows to unify query analysis and expansion by jointly determining the importance weights for the query and expansion concepts depending on their type and source. Experiments using a collection of PubMed articles and TREC Clinical Decision Support (CDS) track queries indicate that applying our proposed method results in significant improvement of retrieval accuracy over state-of-the-art methods for ad hoc and medical IR.
Fortune Innovations is experienced and creative web Design Company which offers web design and Web development service, Mobile application development and GDS Reservation system with SEO features.
EVALUATION AND RECENT TECHNIQUES OF TRANSDERMAL DRUG DELIVERY SYSTEM”.pptxRahulBGole
PRESENTATION OUTLINE
1.Introduction
2.Evaluation Of Transdermal Drug Delivery System
2.1 Physicochemical Evaluation
2.2 In Vitro Release Studies
2.3 In Vivo Evaluation
2.4 Cutaneous Toxicological Evaluation
3. Recent Techniques For Enhancing TDDS
3.1 Structure Based Enhancemnet Techniques
3.2 Electrically Based Enhancement Techniques
3.3 Velocity Based Enhancement Techniques
3.4 Other Enhancement Techniques
4. Conclusion
5. References
1.Introduction :Transdermal drug delivery systems (TDDS), also known as ''patches,'' are dosage forms designed to deliver a therapeutically effective amount of drug across a patient's skin.
2.Evaluation of Transdermal Drug Delivery System:
2.1Physicochemical Evaluation:
Physicochemical Evaluation
In Vitro Release Studies
In Vivo Evaluation
Cutaneous Toxicological Evaluation
2.2. In Vitro Release Studies
●The Paddle over Disc:
The transdermal system is attached to a disc or cell resting at the bottom of the vessel which contains medium at 32 ±5°C.
●The Cylinder modified USP Basket:
The system is attached to the surface of a hollow cylinder immersed in medium at 32 ±5°C.
●Franz diffusion cell:
The cell is composed of two compartments: donor and receptor. The receptor compartment has a volume of 5-12ml and effective surface area of 1-5 cm.The diffusion buffer is continuously stirred at 600rpm by a magnetic bar.
2.3. In Vivo Evaluation
●Animal models:
The most common animal species used for evaluating transdermal drug delivery system are mouse, hairless rat, hairless dog, hairless rhesus monkey, rabbit,guinea pig etc.
●Evaporative water loss management:
Content irritation also disrupts the stratum corenum barrier and causes and excessive water loss from the damaged surface that can be measured means of evaporimetry.
3. Recent Techniques for Enhancing TDDS
3.1. Structure-Based Enhancement Techniques
●Macroflux:
This technology offers a needle-free and painless transdermal drug delivery of large-molecular-weight compounds such as insulin,several peptidic hormones, and vaccines.
●Microfabricated Microneedles:
A transdermal patch or skin adhesive patch is that device which is loaded with drug candidate and usually applied on the skin to transport a specific dose of medication across the skin and into the blood circulation.
3.2.Electrically-Based Enhancement Techniques
●Ultrasound:
In this technique, there is a mixing of drug substance with a coupling agent (usually with gel, cream or ointment) that causes ultrasonic energy transfer from the system to the skin.
●Iontophoresis:
permeation of ionized drug through electrical impulses of 0.5 mA/cm by either galvanic or voltaic cell. It contains cathode and anode which attracts positively charged ion and negatively charged ions, respectively
3.3. Velocity Based Enhancement Techniques:
●Needle-Free Injections:
The liquid or solid particles are fired at supersonic speeds through the outer layers of the skin using a reliable energy source for delivering the drug.
transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream
Emerging trends in transdermal drug delivery technology.pptx version 1-1.pdfPrajaktaPatil890246
The presentation overviews on Introduction to transdermal drug delivery system, Various TDDS technologies that includes active and passive methods . Active delivery methods containing iontophoresis, sonophoresis,electroporation,micro needles,Thermal ablation ,whereas passive delivery method consisting of vesicles and nanoparticles .It also explain various challenges and opportunities for transdermal drug delivery system.
Microneedles are a type of micromachined structure that promotes the transport of substance through an interface or media, via enhanced permeability or microchannels. In most cases, microneedles are similar in shape to hypodermic needle but are much smaller in size, enabling localized and painless delivery of drugs into cells or tissues. It have its own use,advantages and disadvantages.
Similar to Penetration enhancer with their examples (20)
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
2. 2
Flow of Presentation
Introduction
Drug Delivery Routes Across Human Skin
Properties For Ideal Penetration Enhancers
Uses of Penetration Enhancers
Merits And Demerits of Penetration Enhancers
Classification of Penetration Enhancers
Physical Enhancers
References
VNS Group of Institutes
3. INTRODUCTION
3
Penetration enhancers:
Substances used to increase permeation of skin mucosa.
Increases the absorption of penetrant through the skin.
Synonyms: absorption promoter and sorption accelerants.
VNS Group of Institutes
4. Permeation occur by diffusion via
1. Transdermal permeation through the
stratum corneum
2. Intercellular permeation through stratum
corneum
3. Transappendaged permeation via
a. hair follicle
b. sebaceous glands
c. sweat glands
DRUG DELIVERY ROUTES ACROSS HUMAN SKIN
4
VNS Group of Institutes
6. DESIRABLE PROPERTIES FOR IDEAL PENETRATION ENHANCERS
Non-toxic, non-irritating and non-allergic
Rapid working
Predictable and reproducible duration of action
No pharmacological activity within the body
Work unidirectionally
When removed from the skin, barrier properties should return both rapidly and fully
Compatible with both excipients and drugs
Cosmetically acceptable
6
VNS Group of Institutes
7. 1. To increase the delivery of ionisable drugs. Example: timolol maleate etc
2. To deliver the impermeable drugs. Example: heparin etc
3. To maintain level of drug into blood stream
4. To improve the efficacy of less potent drugs with higher dose. Example:
oxymorphane
5. To deliver the drugs having high molecular weight like peptide and hormones
6. To decrease lag time of transdermal drug delivery system
7
USES OF PENETRATION ENHANCERS
VNS Group of Institutes
8. 8
Merits of Penetration Enhancers
1) Most drugs penetrate at rates sufficiently high for therapeutic efficiency by
using penetration enhancers
2) It is useful for unabsorbable drugs to facilitate their absorption through skin
3) It can improve transdermal absorption of topical preparation
4) No adverse effect on skin
5) Do not affect zero order skin permeation profile of skin
6) The terpenes like limonene in propylene glycol solution are effective
penetration enhancer for cytotoxic drugs
VNS Group of Institutes
9. 9
1. The effective concentration varies from drug to drug
2. The uses of different penetration enhancer with various concentrations are
restricted completely
3. Physicochemical properties of enhancers are also affecting the side effects in
the body
Demerits of Penetration Enhancers
VNS Group of Institutes
10. VNS Group of Institutes
10
PENETRATION
ENHANCERS
Chemical
enhancers
Physical
enhancers
Drug vehicle
based
Natural
penetration
Miscellaneous
Biochemical
approach
CLASSIFICATION
11. 11
Mechanism of action:
1. By distruption of highly ordered structure of stratum corneum lipid
2. By interaction with intercellular protein
3. By improved partition of the drug or solvent into stratum corneum
Examples:
Sulfoxide- DMSO, DMF, DMAC
Azones
Surface active agents- SLS, BKC
Amines & amides- urea
Fatty acids etc
VNS Group of Institutes
12. 12
Mechanism of action :
Interaction of enhancers with stratum corneum and development of SAR for
enhances with optimal characteristics and minimal toxicity.
Examples Ion pairs and complex Coacervates chemical potential adjustment.
Drug selection.
VNS Group of Institutes
13. 13
1. Terpenes-
Menthol, Linalool,
Limonene, Carvacrol
2. Essential oil-
Basil oil, Neem oil,
Eucalyptus oil
Mechanism of action :
It may increase one or more of following effects
1. Partition coefficient
2. Diffusion coefficient
3. Lipid Extraction
4. Drug Solubility
5. Macroscopic Barrier Perturbation
6. Molecular Orientation of Terpenes Molecule
with Lipid Bilayer
Examples
VNS Group of Institutes
16. 16
1. Iontophoresis
• Iontophoresis is defined as “the application of a small electric current (0.5
mA/cm2 or less) with a low voltage, to drive ionic and polar molecules
across the skin and into the tissues”
• Used to deliver molecules such as neutral and charged molecules, low and
high molecular weight drugs namely phenobarbital, ranitidine and
zidovudine
VNS Group of Institutes
18. 18
2. Microneedle Array
MN arrays are composed of multiple micron-
sized projections which are typically assembled
on one side of a supporting base or patch
Length- 25μm to 2000μm
Therefore they can create little holes in the
stratum corneum without pain and become the
effective way to enhance the delivery of
therapeutic molecules and macromolecules
VNS Group of Institutes
19. 19
3. Sonophoresis
Synonyms-Phonophoresis or Ultrasound
It involves the use of ultrasonic energy to
enhance skin penetration of active substances
Frequency range -20 KHz to 100 KHz
e.g. Drugs given are tetracycline, biomycin
and penicillin for skin diseases
VNS Group of Institutes
20. 20
4. Magnetophoresis
Acts as an external driving force to enhance drug delivery across the skin
Induces alteration in the skin structure that could contribute to an increase in
permeability
e.g. Magnatoliposomes consisting of magnetic particles wrapped in
phospholipid bilayer which are applied for drug delivery, Magnetic resonance
imaging markers for cancer diagnosis
Mechanism of action :
Drug delivery across the membrane by the application of magnetic field
VNS Group of Institutes
21. 21
5. Electroporation
• It involves the application of short, high
voltage pulses to skin
• Skin electroporation, also called
electropermeabilization, creates transient
aqueous pores in the lipid by application of
high voltage of electrical pulses of
approximately 100–1000 V/Cm for short
time (milliseconds)
VNS Group of Institutes
22. 22
6. Thermophoresis
Thermal energy when applied to skin, cause increased skin
permeability
Heating during topical application of a drug dilates penetration
pathway in the skin and increase kinetic energy and movement of
particles in the treated area which facilitates drug absorption
VNS Group of Institutes
23. 23
7. Radiofrequency
It involves exposure of the skin to a high frequency alternating current of 100
KHz that result in the formation of heat-induced microchannels in the cell
membrane.
Rate of drug delivery is controlled by number and depth of microchannels
formed which depends on the properties of microelectrodes in contact with the
skin during treatment.
e.g. Skin delivery of testosterone and growth hormones.
VNS Group of Institutes
24. 24
• Permeability varies according to skin condition
• Hydrated skin is more permeable than dry skin
• Hydration of skin reduces resistance by loosening the
packaging of layers of stratum corneum
8. Hydration of stratum corneum
VNS Group of Institutes
25. 25
Chemical peels- for superficial or light (epidermal), medium (epidermal–dermal
junction) or deep (deep papillary or papillary reticular dermis) treatments
Microdermabrasion which uses a stream of aluminium oxide crystals
Dermabrasion which employs a motor-driven abrasive fraise or cylinder
Laser ablation applies high- powered pulses to vapourise a section of the horny layer
Adhesive tape- To remove stratum corneum prior to drug application
A microinfusor device- To deliver peptides, proteins and other macromolecules
9. Stripping of stratum corneum
As the horny layer usually provides the permeation barrier, for
efficient drug delivery it can be removed by following techniques:
VNS Group of Institutes
26. 1) Maghrabya, G. M. M. E., Michael, C., Barrie, C. F., 2005. International Journal of
Pharmaceutics 305, 90–104
2) Barry, B. W., 2001. European Journal of Pharmaceutical Sciences 14, 101 –114
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VNS Group of Institutes
