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MICROCHANNEL BASED TRANSDERMAL DELIVERY

USING RADIO FREQUENCY: A NOVEL APPROACH

Name : Parikh Ankitkumar

Yogeshbhai.

College: Institute of pharmacy;

Nirma university,

Year: 4th year

E mail id:[email protected]

o.in

Profile link:

http://www.pharmainfo.net/

ankit

Name: Shah Jigar Nareshkumar -

FacultyCollege: Institute of Pharmacy,

Nirma University,

Ahmedabad.Email id: [email protected],

[email protected]

Profile link:


jigsh12

Author Co-author

mailto:[email protected]


http://www.pharmainfo.net/ankit




http://www.pharmainfo.net/jigsh12














IntroductionDEFINATION:

Transdermal permeation (percutaneous absorption):

• The passage of substance from the outside of the skin

through its various layers into the bloodstream.

• Transdermal permeation

• Transdermal permeation

DrugParticles



Basic Advantages of transdermal

delivery system

• Avoids first-pass effect

• Allows effective use of drugs with short biological

half-life

• Allow administration of drugs with narrow

therapeutic window

• Provides controlled plasma level of very potent drugs

• Drug input can be promptly interrupted when toxicityoccurs

• Increased patient compliance



Disadvantages of TDS

• Drug that require high blood levels cannot be

administered

• Adhesive may not adhere well to all types of skin

• Drug or drug formulation may cause skin irritation or

sensitization

• Uncomfortable to wear

• May not be economical.



Factors Consideration for TDS

development

• Skin Characteristics

• Bioactivity of drug

• Formulation

• Adhesion

• System design



The Structure of Human Skin:



Factor influence the transdermal route

• Time scale of permeation (steady-state vs.

transient diffusion)

• Physicochemical properties of penetrant (pKa,

molecular size, stability, binding affinity,

solubility, partition coefficient)

• Integrity and thickness of stratum corneum

• Density of sweat glands and folicles

• Skin hydration

• Metabolism

• Vehicle effects



Process of transdermal permeation



Various approachesVarious approches

Passive Active

Suffers from various

limitations, primarily

due to lack of

permeability of many

drugs & skin nature.

Iontophoresis ElectroporationMicrochannel

based system

Micro -needle

Rfsystems

V i A h



Various Approaches

a) Transdermal diffusion, possibly in the presence of a chemical enhancer, takesplace by a tortuous route across the stratum corneum, winding around cells andoccurring along the interfaces of extracellular lipid bilayers.b) Low-voltage electrical enhancement by iontophoresis can make transport

pathways through hair follicles and sweat ducts more accessible.c) High-voltage enhancement by electroporation has been shown to occur viatranscellular pathways made accessible by disrupting lipid bilayers. Theapplication of ultrasound seems to make pathways a and c more permeable bydisorganizing lipid bilayer structure.d) Microneedles and RF cell ablation create micron-scale holes in skin to

provide pathways for drug transport.



Limitation of passive & various active

drug delivery system

• Most of the methods suitable for small

molecules

• Not practical enough to offer viable solutions

for pharmaceutical needs. This is due to

various limitations such as an insufficient

delivered dose or duration of delivery.

• Electric charge required (Iontophoresis)

• Required pH environment for effective

delivery of drug



Micro channel based trans delivery

system using RF

• A novel system for active transdermal drugdelivery, based on creating microchannels in the

skin using radio-frequency (RF) electrical current.

• This novel and unique approach provides various

advantages such as;

- A predicted and precisely controlled drug delivery

rate,

- Efficient delivery of a wide range of molecular sizesincluding proteins and other macromolecules,

- A convenient, pain-free system suitable for self

application at home.

t



cro c anne ase trans e very

system using RF



Principle

•It is based on principle of RF ablation, a well-known medical technology to eliminate living

cells which used to cut through tissues in

minimally invasive operations or to destroy

small tumors in the kidney and liver by passing

an alternating electrical current at a frequency

above 100 KHz (radio frequency) through the

area.



Method

Application of RF

device by placing aclosely spaced array

of tiny electrodes with

very precise

dimensions against the

skin

Alternating electrical current is

transferred through each of the

microelectrodes

Cell ablation and form the

microscopic passage

Formation of RFmicrochannels with

consistent, well-

controlled depths

Application of transdermal patch

and microchannels serve as

aquatic channels into the inner

layers of the skin



Passig

current

electrode

patch Formationofmicrochanne

l

Release ofdrug



Drug delivery device

• The system consists of the device, which is used to

pretreat the skin and form the RF microchannels in

the outer layers of the skin, and a patch containing the

drug, which is placed on top of the pretreated skin.

(a) THE DEVICE

(b) THE MICROELECTRODE ARRAY

(c) THE PATCH



Stained microchannel

Eff t f t h t h l



Effect of patch technology on

pharmacokinetic profiles:

• For drug delivery, the microchannels may last up to24 h. At 36 h, the delivery through treated skin

returns to the values of intact skin.

•To achieve a sustained drug flux for 24 h,incorporating the active material into a moist matrix

such as a hydrogel that serves as an infinite reservoir.

• The study was conducted on six healthy adult

volunteers in each test group by Galit Levin. Theresults revealed differences in the plasma-drug levels

and profiles between the treatments.

Eff t f t h t h l




pharmacokinetic profiles

• The results revealed differences in the plasma-drug levels andprofiles between the treatments studied by Galit Levin.

Eff t f t h t h l





• The transdermal delivery through microchannels

resulted in a concentration increase up to 9h and

a constant level up to 24 h.

• This finding confirms that RF microchannel

formation is uniform and reproducible.

• A microelectronic system based on RF cell

ablation using printed-protein patches resultedin very high bioavailability of up to 40%.

Eff t f t h t h l





Table shows the bioavailability of three drug molecules studied by Galit Levin.



Factors influences this system:

•Molecular size of the molecule delivered

• Water solubility

• Concentration

• Microchannel density• Duration of delivery

• Dosage forms

• Drug profile• Type of patches

• Drug accumulation.

F i fl hi



Factors influences this system • Molecular size: In case of small-molecule drugs, size

can be increased significantly by pretreatment & formacromolecules, like peptides and proteins, also help

in delivering them systemically through the skin by

this technology.

• Water solubility: Water-soluble molecules, can be

easily delivered. Water-insoluble drugs can be

delivered by increasing the water solubility through a

suitable formulation.• Concentration: In contrast to any passive delivery, It

is help in increasing the drug concentration on the

skin in the vicinity of the microchannels will result in

a higher delivery rate.

F i fl hi



Factors influences this system

• Microchannel density: By increasing the

microchannel density (MCs/cm2

), a higher amount of drug can be delivered in efficient manner.

• Duration of delivery: The drug delivery can be

enhanced up to 24 h using this technology

• Dosage forms: A patch is the most convenient

dosage form for drug delivery. Beside this, gels,

Creams & the other semisolid dosage forms can be

used.• Drug profile: The result of the transdermal delivery

using RF cell ablation can be a peak-plasma profile or

a constant blood level, depending on the type of patch

technology used

F t i fl thi t



Factors influences this system

• Type of patches: A reservoir patch, usually a water-

based hydrogel, can be used to incorporate small or

large molecules and apply them on the skin. For

proteins, the use of a printed patch is advisable for

stability purposes.• Lack of reservoir in the skin: In contrast to passive

delivery, the microelectronic system based on RF cell

ablation used in this study delivered water-soluble

drugs that cannot be accumulated in the lipidicstratum corneum. No issue of reservoir formation

exists.



Main Application

For protein

delivery

For hydrophilic

drug &

hydrophobic

drug

For

macromole-

cules



Patch technology for protein delivery:

• Transdermal delivery of large proteins is a novel and

exciting method because no commercial technologycurrently available incorporates proteins intotransdermal patches.

• The manufacturing method involves dispensing very

small droplets of a concentrated protein solution on atransdermal liner in a predetermined pattern.

• The liquid is dried, leaving a dry and thin layer of formulated protein on top of the liner.

• The highly water-soluble proteins are dissolved bythe interstitial fluid that is secreted from the skinthrough the RF microchannels, thus forming a highlyconcentrated protein solution in situ.



Patch technology for protein delivery:



P h h l f h d lili



Patch technology for hydroplilic

drug & hydrophobic drug

• Under this technique, pretreating the skinallows aquatic channels to form across thestratum corneum, which provides significantenhancement in the permeability of water-soluble compounds.

• Drugs that exhibit insufficient solubility inwater can still benefit from the technology.

•By increasing solubility using variousformulation approaches, such as drug-cyclodextrin complexes or dissolving the drugin a water-alcohol mixture, the drugs are also

able to permeate the skin.





drug & hydrophobic drug•Table I shows the in vitro skin permeability of various

drugs in a dynamic diffusion-cell model using full-

thickness porcine skin. The results show enhanced

transdermal delivery with the hydrophilic

compounds —

granisetron hydrogen chloride (HCl) andlidocaine HCl which is study by Galit Levin.





drug & hydrophobic drug

• The results show enhanced transdermal delivery

with the hydrophilic compounds — granisetron

hydrogen chloride (HCl) and lidocaine HCl.

Lidocaine HCl is more water-soluble thandiclofenac sodium and had higher delivery rates.

• The effect of the compound concentration on its

delivery rate was shown with testosterone (2%

versus 6% in aqueous solution) and lidocaine HCl

(2% versus 5% in aqueous solution).

• The delivery rate increased linearly with the

concentration of the loaded compound.



Patch technology for Macromolecules

• The delivery of these macromoleculesthrough a full-thickness porcine skin that

had been pretreated with the device. An

increase in molecular size brought abouta decrease in delivery rate.

• The largest 70-kDa molecule was

successfully delivered transdermally

through the RF microchannels.



Advantage over otherconventional techniques

A convenient, painless,

and less invasive

alternative to injection, a

common method for

administering largeproteins and peptides in

low manufacturing cost.

In contrast to oral delivery ,

this avoid first pass effect and

offers the benefit of

immediate cessation of drug

administration in case of an

adverse effect or overdose.

In contrast to passive

delivery , this allow for

the delivery of water-

soluble drugs

In contrast to Iontophoresis , this

is use for long time There is alsono molecular size limitation, no

molecular electrical charge

requirement, and no specific

formulation pH constraint.

In contrast to micro needle ,

this is use for potent & less

potent drug, the more

extended release the delivery

system

So, Microchannel based Trans Delivery

System by using Radio Frequency ( RF) is

a Novel Approch for Drug delivery system

Acknowledgement



Acknowledgement • Writing this acknowledgement has provided me with the great

opportunity to note the enormous help & guidance given by

various persons whose work was note worthy & can’t bediminished from my mind & soul.

• I would like to thank www.pharmainfo.net to give me

opportunity of presenting power point presentation regarding

my interested topic.• I would like to thank our principal Dr. Avani F. Amin & other

faculty members who encourage me for this purpose.

• I would also like to thank librarian of my institute for giving

me permission to utilize our library resources.• Finally, I would like to mention a very special thank to my co-

author who give me his valuable time, support and constant

guidance with continuous suggestions to make this

presentation very effective.

References









References• B. Decadt and A.K. Siriwardena, "Radiofrequency Ablation of

Liver Tumors: A Systematic Review," Lancet Oncol.5 (9),

550 – 560 (2004).• A. Hines-Peralta and S.N. Goldberg, "Review of

Radiofrequency Ablation for Renal Cell Carcinoma," Clin.

Cancer Res. 10 , 6328S – 6334S (2004).

• S. Nahum Goldberg, "Radiofrequency Tumor Ablation:Principles and Techniques," Eur. J. Ultrasound 13 (2), 129 –

147 (2001).

• L. Solbiati et al., "Radiofrequency Thermal Ablation of

Hepatic Metastases," Eur. J. Ultrasound , 13 (2), 149 – 158(2001).

• F.J. McGovern et al., "Radiofrequency Ablation of Renal Cell

Carcinoma via Image Guided Needle Electrodes," J. Urol. 161

(2), 599 –

600 (1999).

References



References • A.S. Sintov et al., "Radiofrequency-driven Skin

Microchanneling as a New Way for Electrically Assisted

Transdermal Delivery of Hydrophilic Drugs," J. Controlled Release, 89 (2), 311 – 320 (2003).

• Z. Avrahami, "Transdermal Drug Delivery and Analyte

Extraction," US Patent No. 6,148,232 (2000).

• Z. Sohn and Z. Avrahami, "Monopolar and Bipolar CurrentApplication for Transdermal Drug Delivery and Analyte

Extraction," US Patent No. 6,611,706 (2001).

• G. Levin et al., "Transdermal Delivery of Human Growth

Hormone through RF-Microchannels," Pharm. Res. 22 (4),550 – 555 (2005).

• M.R. Prausnitz, S. Mitragotri, and L. Langer, "Current Status

and Future Potential of Transdermal Drug Delivery," Nature

Rev. Drug Disc.3 (2),115 –

124 (2004).



Thank you

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