Methods For Monitoring Transdermal Drug Delivery

Analytical/Radio/Nuclear (ARN) Seminar

Jivan YewleDepartment of Chemistry

University of Kentucky

Overview Introduction Skin Physiology Transdermal Drug Delivery (TDD) Methods For Monitoring TDD

Confocal Laser scanning microscopy (CLSM) Two photon fluorescence microscopy (TPFM) Infrared Microscopic Imaging Raman Microscopic Imaging

Instrumentation Applications Advantages and Limitations

Introduction

Types of Drug Delivery system Oral Drug Delivery Intravascular Drug Delivery Transmucosal Drug Delivery Transdermal Drug Delivery (TDD)

Skin Physiology

Epidermis

Dermis

Subcutaneous tissue

Stratum corneum

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Skin Physiology

Characteristics: Tough Flexible Poor conductor of electricity

Functions of skin: To protect the body from external insults To contain all body fluids To regulate body temperature To protect from electrical current

Transdermal Drug Delivery

Delivery of drug through skin Drugs (birth control patches, nicotine patches)

Transdermal patches

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Transdermal Drug Delivery

Mechanism Penetration

Intercellular route Follicular route

Diffusion

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Transdermal Drug Delivery

Advantages of TDD: Steady permeation of drug across skin Controlled drug delivery Good for acid and enzyme reactive drugs. Minimum risk of side effects Limited toxic effects (if) Convenience : may require only once weekly Easy drug administration Good for lipophilic drug molecules

Transdermal Drug Delivery

Disadvantages and limitations of TDD Possibility of a local irritation Allergic reactions are possible Risky for children Skin's low permeability Molecular size and polarity of drug Insufficient bioavailability Damage to a transdermal patch

Transdermal Drug Delivery Strategies for improving transport rate

Penetration enhancers(eg: Water, Terpenes, Oleic acids, Menthol, Azones ) Reduces barrier function of skin Some penetration enhancers remove lipids

from the skin Water: a natural penetration enhancer Alcohol: a solvent as well as a penetration

enhancer

Transdermal Drug Delivery Strategies for improving transport rate

Liposomes (Lipid vesicles) Spherical vesicles with a membrane composed

of a phosholipid bilayer Created by sonicating phospholipids in water Encapsulates drug molecule Lipid bilayer can fuse with other bilayers It neither penetrates nor fuses to SC It can be sensitive to temp, pH, light etc.

Instrumental tools for monitoring TDD

1. Confocal Laser scanning microscopy (CLSM)

2. Two photon fluorescence microscopy (TPFM)

3. Infrared Microscopic Imaging4. Raman Microscopic Imaging

1. Confocal Laser scanning microscopy

Instrumentation

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1. Confocal Laser scanning microscopy

Applications in TDD Images parallel to skin surface Position of drug molecule under skin surface Information about penetration of drug

Other applications Evaluation of biological phenomenon Transport studies through biological membrane Surface study of different material

1. Confocal Laser scanning microscopy

Advantages Images of thick specimens at various depth 3D confocal images High degree of precision Blur-free images

Limitations and disadvantages Information about permeation of fluorescent

label only Images up to 25 m depth only Smaller signal to noise ratio

2.Two Photon fluorescence microscopy

Instrumentation

2.Two Photon fluorescence microscopy

Applications in TDD

Deeper images of skin up to 1mm

Position of drug molecule under skin surface

Information about penetration of drug

2.Two Photon fluorescence microscopy

Advantages Imaging up to depth of 1mm Deeper tissue penetration Reduced phototoxicity Use of infrared light to excite fluorophores High-resolution imaging.

Limitations Substance to be studied should have

fluorophores

Methods For Monitoring TDD3. Infrared Microscopic Imaging

Instrumentation

3. Infrared Microscopic Imaging

Application in TDD1,2-dipalmitoylphosphatidylcholine (DPPC-d62)

C. Xiao, C.R. Flach, R. Mendelsohn. J Invest Dermatol. (2005), 124, 622-632

CD2-Symm/asymm-2100/2200

Amide-1650/1550CH2-stre-2850-2920

3. Infrared Microscopic Imaging

Advantages Sampling of much greater area (few mm) Higher signal to noise ratio

Limitations Unsuited to cofocal application Limited applications for in vivo potential Low spatial resolution (10-12 m) Requires careful sectioning of the skin (5 m)

Methods For Monitoring TDD4. Raman Microscopic Imaging

Application in TDD

CD2 Stretching

2000-2080 cm-1

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C. Xiao, C.R. Flach, R. Mendelsohn. J Invest Dermatol. (2005), 124, 622-632

4. Raman Microscopic Imaging

Advantages Non-intrusive and non-destructive Analysis at various temperatures Analysis within sealed systems Direct spatially resolved concentration Molecular structure information Higher spatial resolution (1-2 m)

4. Raman Microscopic Imaging

Applications Surface and materials science Forensic research / investigation Polymer science Geology Pharmaceutical science

Limitations Possibility of errors

Summary

Transdermal drug delivery is an effective technique for steady and consistent drug delivery.

Penetration enhancers and liposomes are good solutions for the slow permeation of the skin.

IR and Raman Microscopic imaging techniques are more useful than others to monitor TDD.

References1. I.V. Zhigaltesv, N. Maurer. Biochemicaet Biophysica Acta. (2002),

1565, 129-135.2. C. Xiao, C.R. Flach, R. Mendelsohn. J Invest Dermatol. (2005), 124,

622-632.3. K.M.Hanson, R.M.Clegg. Biophys J. (2002), 83, 1682–1690.4. E.N.Lewis,P.J.Treado. Anal Chem. (1995), 67, 3377–3381.5. C.Xiao, R.Mendelsohn. Appl Spectrosc. (2004), 58, 382–389.6. P.J.Caspers, G.J.Puppels. Biospectroscopy (1998), 4, S31–S39.

7. www.uspharmacist.com8. http://en.wikipedia.org9. www.shef.ac.uk

Acknowledgements

Dr. Vasilios Gavalas University of Kentucky

Chemistry Department