Summary and Definitions
- •There is not one standard technique by which the bioavailability of all topical drugs can be assessed.
- •The most commonly used techniques are in vitro (Franz cell chamber), ex vivo (isolated perfused skin models), and in vivo (vasoconstrictor assay, tape stripping/dermatopharmacokinetics, and microdialysis).
- •Franz cell chamber: A two-compartment system, separated by excised skin or membrane, that allows calculation of the amount of topical drug that is absorbed through the skin or membrane from the donor compartment to the receptor compartment.
- •Isolated perfused skin models: A section of animal skin or an organ, commonly a porcine skin flap, bovine udder, or porcine forelimb, is surgically isolated, then cannulized and perfused with tissue-culture medium and continuously sampled for topically applied drugs.
- •Vasoconstrictor assay: A technique that uses the blanching effects of topical corticosteroids as a surrogate marker for their bioavailability.
- •Tape stripping/DPK: A technique that measures the amount of topical drug in the stratum corneum using tape strips at sequentially increasing time intervals from the time of application.
- •Microdialysis: A technique that involves implantation of a probe with a semipermeable membrane into the dermis or hypodermis, allowing continuous monitoring of topical drugs in the interstitial fluid.
In Vitro Techniques
Franz cell chamber
Ex Vivo Techniques
Isolated perfused skin models
In Vivo Techniques
|Franz/Bronaugh Cell Chamber|
|Perfused skin models|
|Open flow microperfusion|
Conflict of Interest
Multiple Choice Questions
- 1.Which of the following types of skin and/or membrane is typically preferred in the Franz/Bronaugh cell chamber?
- A.Human skin
- B.Animal skin
- C.Artificial membrane
- D.All of the above are equally preferred
- 2.What is a unique advantage of isolated perfused skin models?
- A.Allows assessment of the bioavailability of any topical drug
- B.Takes into consideration the effects of microcirculation and metabolism, without systemic involvement
- C.Allows the blanching effects of topical drugs to be used as a surrogate marker for bioavailability
- D.Uses human skin without requiring live human subjects
- 3.What causes the unique blanching effects of topical corticosteroids?
- C.Local vasoconstriction
- 4.Why are tape strips always weighed before and after application when they are used to determine the bioavailability of topical drugs?
- A.To increase the absorption of the topical drug
- B.To use the data in other experiments
- C.To standardize various tape strip and stratum corneum variables
- D.No particular reason
- 5.If the test drug is lipophilic, what adjustment can be made to the microdialysis technique to improve outcomes?
- A.Add solvents to the solution to allow better solubility
- B.Increase the flow rate to 100–200 μl/min
- C.Repeat the study multiple times
- D.No adjustments can be made
- Quiz and brief explanation of correct answers
- Teaching Slides
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- Bioequivalence of topical formulations in humans: evaluation by dermal microdialysis sampling and the dermatopharmacokinetic method.J Invest Dermatol. 2007; 127: 170-178
- Topical absorption of dermatological products.Marcel Dekker, New York2002
- Drug absorption studies: in situ, in vitro, and in silico models.Springer, New York2008
- In vivo methods for the assessment of topical drug bioavailability.Pharm Res. 2008; 25: 87-103
- Dermatopharmacokinetic prediction of topical drug bioavailability in vivo.J Invest Dermatol. 2007; 127: 887-894
- Dermal and ocular toxicology: fundamentals and methods.CRC Press, Boca Raton1991
- Strategies for the bioequivalence assessment of topical dermatological dosage forms.J Bioequiv Availab. 2010; 2: 102-110
- Correlation of skin blanching and percutaneous absorption for glucocorticoid receptor agonists by matrix-assisted laser desorption ionization mass spectrometry imaging and liquid extraction surface analysis with nanoelectrospray ionization mass spectrometry.Anal Chem. 2010; 82: 7787-7794
- Study of in vitro drug release and percutaneous absorption of fluconazole from topical dosage forms.AAPS PharmSciTech. 2010; 11: 986-993
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- The comparability of in vitro and ex vivo studies on the percutaneous permeation of topical formulations containing ibuprofen.Altern Lab Anim. 2012; 40: 91-98
- Application of dermal microdialysis for the evaluation of bioequivalence of a ketoprofen topical gel.Eur J Pharm Sci. 2009; 36: 219-225
- Current challenges in bioequivalence, quality, and novel assessment technologies for topical products.Pharm Res. 2014; 31: 837-846
- Dermatotoxicology (6th ed).CRC Press, Boca Raton2004
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