Transdermal Drug Delivery – Assessment of in vitro skin permeation

Shashank Jain

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Introduction

• Transdermal and topical drug delivery

• Advantage-Site specific applicationFirst pass metabolismAvoid GI side-effectsControlled drug deliveryNon-invasive

• Limitation-DoseLarge moleculesSkin irritation and metabolismRate limiting stratum corneum

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Skin structure

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Pathways for drug permeation

Stratum corneum

Epidermis

Dermis Blood

supply

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Approaches• Physical:

MicroneedleIontophoresisElectrophoresis

• Chemical:EthanolPEG

• Colloidal:LiposomeEthosomesMicroemulsion

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Iontophoresis

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Ethosome

Mechanism of skin delivery via ethosome vesicles*

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Assessment of in-vitro permeation• Fick’s law of diffusion

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A] Side-Bi-Side

In-vitro experiment setup

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In-vitro experiment setup(contd.) B] Vertical Franz

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In-vitro experiment setup (contd.) C] Flow Through Cells:

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In-vitro permeation study procedure• Step 1. Skin selection

Human skinAnimal skin Human skin equivalent

• Step 2. Isolating skin section• Step 3. Experimental setup

Mounting skin sectionTemperatureAir bubble

• Step 4. Sampling• Step 5. Drug deposition study• Step 6. Data analysis

Permeation fluxCumulative drug permeationDrug deposition

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A typical permeation profileC

umul

ativ

e dr

ug

perm

eate

d/ar

ea

Time

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References:• Naik, A., Kalia, Y.N., Guy, R.H., 2000. Transdermal drug delivery:

overcoming the skin’s barrier function. Pharmaceutical Science & Technology Today 3, 318-326

• Verma, P., Pathak, K., 2010. Therapeutic and cosmeceutical potential of ethosomes: An overview. J Adv Pharm Technol Res 1, 274-282

• http://www.permegear.com/primer.pdf

• Bolzinger, M.-A., Briancon, S.p., Pelletier, J., Chevalier, Y., 2012. Penetration of drugs through skin, a complex rate-controlling membrane. Current Opinion in Colloid & Interface Science 17, 156-165.

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Thank You

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• Document BA/BE in order of preference are (1) pharmacokinetic (PK) measurements based on measurement of an active drug and/or metabolite in blood, plasma, and/or urine; (2) pharmacodynamic (PD); (3) clinical trials; and (4) in vitro studies.

• The BA/BE determination based on PD (or clinical) and dermatokinetics.

• DPK encompasses drug concentration measurements with respect to time, based on a stratum corneum concentration-time curve

• Topical: If two formulation produce comparable stratum corneum concentration-time curves may be BE

• A plot of stratum corneum drug concentration versus a time profile should be constructed to yield stratum corneum metrics of Cmax, Tmax and AUC.

• Transdermal delivery systems, are considered to be bioequivalent if they yield comparable bioavailability-based plasma concentration–time profiles when administered to the same individuals under similar dosage conditions.

• Two oral or transdermal formulations are judged BE if they produce comparable plasma concentration-time curves.