Science & Research

Assessment of the In Vitro Percutaneous Absorption, In Vitro Rate of Release, and Physicochemical Properties of Selected Commercially Available AT-rated Ointment Formulations

Principal Investigator: Paul A. Lehman

Performer: QPS, LLC

Project Duration: 09/29/2016 – 12/31/2017

Regulatory Science Challenge:

Several generic ointment formulations have been approved by the FDA as being therapeutically equivalent—having AT ratings—to that of the reference listed drug (RLD) formulations. However, even AT-rated ointments may not be similar in terms of the microstructure. For locally acting topical ointments, differences in microstructure can mean that the rates of release of the active drug from the ointment matrix as well as percutaneous absorption kinetics are not the same as RLD, and this can lead to variations in clinical effectiveness, and even degree of safety. There are several factors that can contribute to this difference: differences in manufacturing processes, excipient quality and purity, as well as physicochemical properties (particle size, dispersion, and solubility of active pharmaceutical ingredient (API) in the vehicle matrix).

This project involved comparison of the topical bioavailability of API from commercially-available AT-coded ointments with that from their respective RLD products. The bioavailability was be evaluated using In Vitro Permeation Tests (IVPT), a method that has been shown to correlate with in vivo bioavailability. In addition, the physicochemical properties and associated performance using In Vitro Release Test (IVRT) of the (same) AT-coded ointments and their respective RLD products were compared. The proposed objectives are designed to achieve two goals. First, to test if AT-coded ointment formulations are also bioequivalent with their respective RLDs, such that their rate of drug release and percutaneous absorption kinetics show insignificant difference with those of RLD formulations. Second, to identify which product quality attributes and/or physicochemical properties are correlated with bioavailability, and can be used as the basis for considering topical ointments bioequivalent.

Project Description & Goals:

The study is to develop a systematic approach to assess the in vitro percutaneous absorption, in vitro rate of release, and physicochemical properties of commercially available ointment formulations that are labelled as therapeutically equivalent (having an AT rating).

The study consists of five phases:

  • Conduct in vitro percutaneous absorption using 5 -6 AT-rated formulations
  • Quantify API of interests from samples using HPLC
  • Select two formulations from the first phase, and perform ex vivo studies on 6 donors
  • Perform in vitro rate of release using the two selected formulations
  • Characterize physicochemical properties of the two selected formulations



Page Last Updated: 11/16/2017
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