Transdermal Drug Delivery –
Assessment of in vitro skin
permeation
Shashank Jain
2
Introduction
• Transdermal and topical drug delivery
• Advantage Site specific application
 First pass metabolism
 Avoid GI side-effects
 Controlled drug delivery
 Non-invasive
• Limitation Dose
 Large molecules
 Skin irritation and metabolism
 Rate limiting stratum corneum
3
Skin structure
4
Pathways for drug permeation
Stratum
corneum
Epidermis
Dermis
Blood
supply
5
Approaches
• Physical:
 Microneedle
 Iontophoresis
 Electrophoresis
• Chemical:
 Ethanol
 PEG
• Colloidal:
 Liposome
 Ethosomes
 Microemulsion
6
Iontophoresis
7
Ethosome
Mechanism of skin delivery via ethosome vesicles*
8
Assessment of in-vitro permeation
• Fick’s law of diffusion
9
In-vitro experiment setup
A] Side-Bi-Side
10
In-vitro experiment setup
(contd.)
B] Vertical Franz
11
In-vitro experiment setup (contd.)
C] Flow Through Cells:
12
In-vitro permeation study procedure
• Step 1. Skin selection
 Human skin
 Animal skin
 Human skin equivalent
• Step 2. Isolating skin section
• Step 3. Experimental setup
 Mounting skin section
 Temperature
 Air bubble
• Step 4. Sampling
• Step 5. Drug deposition study
• Step 6. Data analysis
 Permeation flux
 Cumulative drug permeation
 Drug deposition
13
Cumulative drug
permeated/area
A typical permeation profile
Time
14
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.
15
Thank You
16
17
• 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.