Special Issue "Bioavailability and Bioequivalence of Topical Formulations"

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: closed (20 August 2023) | Viewed by 2023

Special Issue Editor

Leslie Dan College of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada
Interests: bioavailability; bioequivalence; dosage form

Special Issue Information

Dear Colleagues,

The market approval of a generic product requires the demonstration of bioequivalence (BE) against an innovator reference product in order to ensure safety and efficacy. Unlike extravascular dosage forms where well-established methods and regulatory guidelines are available for BE assessment, procedures or guidelines for the BE of topical dosage forms intended for local action, apart from the US FDA’s vasoconstrictor assay (VCA), are conspicuously absent. Most regulatory authorities usually require lengthy and expensive comparative clinical endpoint studies in patients. More recently, considerable efforts have been directed towards the development and validation of surrogate models to demonstrate the BE of topical products for local action and facilitate the faster entry of generic products into the market. Requirements ensuring that such topical generic products are designed to match an approved reference product have been set out by regulatory authorities, where emphasis has been placed on specific quality properties such as qualitative (Q1), quantitative (Q2) and—particularly for semi-solid formulations—similarity in formulation microstructure (Q3). Currently, relatively few surrogate approaches to the assessment of the BE of topical dosage forms for local action have been explored. The more prominent methods include tape stripping, dermal microdialysis, open-flow microperfusion and, more recently, the acceptance of biowaivers using in vitro release and permeation tests. In the latter instance, the US FDA has issued specific product guidelines (SPGs) for topicals.

This Special Issue on the bioavailability (BA) and bioequivalence (BE) of topical formulations intended for local action will focus on research and review papers discussing applications of validated methods used to assess BE of topical dosage forms not intended for absorption, and will include both in vivo and in vitro methods.

We welcome articles dealing with all aspects of the BA/BE of topical dosage forms for local action, and invites researchers and drug developers to submit their original research or review articles with expert opinions and perspectives in this area.

Prof. Dr. Isadore Kanfer
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • bioequivalence
  • bioavailability
  • biowaivers
  • topical dosage forms for local action
  • topical corticosteroids
  • vasoconstrictor assay (VCA)
  • skin blanching
  • chromameter
  • tape stripping
  • dermatopharmacokinetics
  • dermal microdialysis
  • in vitro release tests (IVRTs)
  • in vitro permeation tests (IVPTs)
  • ex vivo permeation tests
  • dermal open flow microperfusion (dOFM)
  • confocal Raman spectroscopy
  • near-infrared (NIR) spectrometry
  • product specific guidances (PSG)
  • membrane diffusion
  • pharmaceutical equivalence
  • sameness
  • Q1/Q2/Q3
  • semi-solid dosage forms
  • method validation
  • human skin
  • stratum corneum

Published Papers (1 paper)

Order results
Result details
Select all
Export citation of selected articles as:


In Vitro–In Vivo Correlations (IVIVC) for Predicting the Clinical Performance of Metronidazole Topical Creams Intended for Local Action
Pharmaceutics 2023, 15(1), 268; https://doi.org/10.3390/pharmaceutics15010268 - 12 Jan 2023
Viewed by 1586
The safety and efficacy of a generic medicine can be confirmed by demonstrating bioequivalence (BE) between the generic product and its reference listed drug (RLD) by measuring drug concentrations in the blood following administration. However, for topical dermatological products that are not absorbed [...] Read more.
The safety and efficacy of a generic medicine can be confirmed by demonstrating bioequivalence (BE) between the generic product and its reference listed drug (RLD) by measuring drug concentrations in the blood following administration. However, for topical dermatological products that are not absorbed into the systemic circulation, clinical trials in patients are required. The objective of this investigation was to use an in vitro method to predict in vivo performance by correlating in vitro release testing (IVRT) data with tape stripping (TS) data following the application of metronidazole (MTZ) creams to the skin of healthy human participants. Whereas IVRT is generally used to characterize the release of a drug from topical products across a synthetic membrane into a suitable receptor medium, TS involves the sequential removal of layers of stratum corneum (SC) with an adhesive tape to determine the amount of the drug in the skin. The resulting IVRT and TS data were correlated using the IVRT parameter of the apparent release constant (ARC), which is the slope obtained from the release rate profile, with the TS parameter of the area under the curve (AUC) obtained from a plot of the amount of drug per tape strip vs. the relative SC depth. A rank order relationship for these parameters was established for the reference and test products. A graph of AUC vs. ARC was plotted to establish a Level C in vitro–in vivo correlation (IVIVC). Although the ARC for T1 was slightly lower than that for the reference, the rank order was essentially consistent. A linear relationship was observed between the AUCs and ARCs. The equation derived was used to predict the AUCs for all the tested products based on their respective ARCs. The predicted AUC values based on the observed ARCs were similar to the observed AUCs. The lower and upper limits for the in vitro and in vivo parameters for BE were computed based on regulatory acceptance criteria. In order to predict BE from the IVRT studies, the values of the ARC should be between 30.50 and 47.67 when comparing test and reference cream products containing MTZ. Full article
(This article belongs to the Special Issue Bioavailability and Bioequivalence of Topical Formulations)
Show Figures

Graphical abstract

Back to TopTop