Physiologically Based Biopharmaceutics and Pharmacokinetics of Drug Products for Dermal Absorption in Humans

Information

  • Research Project
  • 8857568
  • ApplicationId
    8857568
  • Core Project Number
    U01FD005232
  • Full Project Number
    1U01FD005232-01
  • Serial Number
    005232
  • FOA Number
    RFA-FD-14-012
  • Sub Project Id
  • Project Start Date
    9/10/2014 - 10 years ago
  • Project End Date
    8/31/2017 - 7 years ago
  • Program Officer Name
  • Budget Start Date
    9/10/2014 - 10 years ago
  • Budget End Date
    8/31/2015 - 9 years ago
  • Fiscal Year
    2014
  • Support Year
    01
  • Suffix
  • Award Notice Date
    9/10/2014 - 10 years ago

Physiologically Based Biopharmaceutics and Pharmacokinetics of Drug Products for Dermal Absorption in Humans

Abstract Here we seek to assist the FDA in its evaluation of topical products by developing, evaluating and improving a framework of physiologically based absorption and pharmacokinetic models for dermal absorption in response to the FDA call: Physiologically Based Absorption and Pharmacokinetic Modeling and Simulation for Non-gastrointestinally Absorbed Drug Products in Humans (RFA-FD-14-012), focusing on dermal absorption. We describe a framework of three physiologically based pharmacokinetic models to assist in this evaluation: 1. An analytical solution based on a Laplace Transform solution 2. A compartmental approach 3. A 3D numerical analysis to precisely mimic the geometry of the stratum corneum and processes that occur when a product is applied to the skin eg evaporation of some excipients, penetration of active and some excipients into the skin and transfer to deeper tissue and the systemic circulation This work is then validated by parameter sensitivity analyses, a comparison with of predictions with actual data observations and some in house validation studies. The final stage is an evaluation of the models using data from 2 CROs and 2 studies FDA are presently supporting that involve in vitro membrane, in vitro skin penetration, in vitro stratum corneum assays, in vivo stratum corneum assays and dermal assays. A key outcome here, as well as an adequate description of the data, is a population description of intra and intersubject variability and likely covariances. Our key goal is to predict active concentrations at their sites of action and in the blood over time.

IC Name
FOOD AND DRUG ADMINISTRATION
  • Activity
    U01
  • Administering IC
    FD
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    200000
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
  • Ed Inst. Type
  • Funding ICs
    FDA:200000\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZFD1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    UNIVERSITY OF SOUTH AUSTRALIA
  • Organization Department
  • Organization DUNS
    756220208
  • Organization City
    ADELAIDE
  • Organization State
  • Organization Country
    AUSTRALIA
  • Organization Zip Code
    5095
  • Organization District
    AUSTRALIA