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Methods For Monitoring Transdermal Drug Delivery

Methods For Monitoring Transdermal Drug Delivery. Analytical/Radio/Nuclear (ARN) Seminar Jivan Yewle Department of Chemistry University of Kentucky. Overview. Introduction Skin Physiology Transdermal Drug Delivery (TDD) Methods For Monitoring TDD

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Methods For Monitoring Transdermal Drug Delivery

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  1. Methods For Monitoring Transdermal Drug Delivery Analytical/Radio/Nuclear (ARN) Seminar Jivan Yewle Department of Chemistry University of Kentucky

  2. 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

  3. Introduction Types of Drug Delivery system • Oral Drug Delivery • Intravascular Drug Delivery • Transmucosal Drug Delivery • Transdermal Drug Delivery (TDD)

  4. Skin Physiology Stratum corneum Epidermis Dermis Subcutaneous tissue www.uspharmacist.com

  5. 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

  6. Transdermal Drug Delivery • Delivery of drug through skin • Drugs (birth control patches, nicotine patches) • Transdermal patches www.uspharmacist.com

  7. Transdermal Drug Delivery Mechanism • Penetration • Intercellular route • Follicular route • Diffusion www.uspharmacist.com

  8. 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

  9. 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

  10. Transdermal Drug DeliveryStrategies 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

  11. Transdermal Drug DeliveryStrategies 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.

  12. Instrumental tools for monitoring TDD • Confocal Laser scanning microscopy (CLSM) • Two photon fluorescence microscopy (TPFM) • Infrared Microscopic Imaging • Raman Microscopic Imaging

  13. 1. Confocal Laser scanning microscopy Instrumentation http://en.wikipedia.org

  14. 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

  15. 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 mm depth only • Smaller signal to noise ratio

  16. 2.Two Photon fluorescence microscopy Instrumentation

  17. 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

  18. 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

  19. Methods For Monitoring TDD3. Infrared Microscopic Imaging Instrumentation

  20. 3. Infrared Microscopic Imaging Application in TDD 1,2-dipalmitoylphosphatidylcholine (DPPC-d62) CD2-Symm/asymm-2100/2200 Amide-1650/1550 CH2-stre-2850-2920 C. Xiao, C.R. Flach, R. Mendelsohn. J Invest Dermatol. (2005), 124, 622-632

  21. 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 mm) • Requires careful sectioning of the skin (5 mm)

  22. Methods For Monitoring TDD4. Raman Microscopic Imaging Application in TDD CD2 Stretching 2000-2080 cm-1 www.shef.ac.uk C. Xiao, C.R. Flach, R. Mendelsohn. J Invest Dermatol. (2005), 124, 622-632

  23. 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 mm)

  24. 4. Raman Microscopic Imaging Applications • Surface and materials science • Forensic research / investigation • Polymer science • Geology • Pharmaceutical science Limitations • Possibility of errors

  25. 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.

  26. References • I.V. Zhigaltesv, N. Maurer. Biochemicaet Biophysica Acta. (2002), 1565, 129-135. • C. Xiao, C.R. Flach, R. Mendelsohn. J Invest Dermatol. (2005), 124, 622-632. • K.M.Hanson, R.M.Clegg. Biophys J. (2002), 83, 1682–1690. • E.N.Lewis,P.J.Treado. Anal Chem. (1995), 67, 3377–3381. • C.Xiao, R.Mendelsohn. Appl Spectrosc. (2004), 58, 382–389. • P.J.Caspers, G.J.Puppels. Biospectroscopy (1998), 4, S31–S39. • www.uspharmacist.com • http://en.wikipedia.org • www.shef.ac.uk

  27. Acknowledgements Dr. Vasilios Gavalas University of Kentucky Chemistry Department

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