MembranePlus™ Modules

Enter MembranePlus™, the industry’s leading mechanistic in vitro permeability & hepatocyte modeling software.

04. MembranePlus™ WHAT & HOW
Novel Approaches

The Transdermal Compartmental Absorption and Transit Module in MembranePlus

  • Allows the user to model in vitro penetration tests (IVPT) and in vitro release tests (IVRT) in static and flowthrough diffusion cells
  • Incorporate formulation characteristics and processes such as solubility, dissolution and precipitation, and vehicle and API evaporation
  • Model diverse topical formulations such as solutions, suspensions, and emulsion formulations
  • Model non-linear vehicle evaporation processes
  • Model permeation processes through the skin or synthetic membranes
  • Incorporate predicted, measured, and/or optimized permeability parameters
  • Model common types of skin samples: dermatomed skin, heat-separated epidermis, full thickness skin, stratum corneum alone for human, minipig, rat, and mouse skin samples
  • Use predicted parameters in GastroPlus for in vitro-in vivo extrapolation

Passive Transport Model Improvements

  • Removed the hard limit on count-based descriptors of 6 for calculation of membrane entry/exit rates. Originally the passive transport model entry and exit rates were only affected by count based descriptor values of up to 6 based on the training set.  Now, we allow users to use their own compound libraries with no cap on count-based descriptors to calculate membrane entry and exit rates.  This was requested to model larger compounds like cyclic peptides.
  • Addition of internal hydrogen bonds to lower the effect of HBAo. Many compounds like cyclic peptides may have many oxygen doners that decrease permeability.  However, the molecule can fold and form internal hydrogen bonds that reduce the overall polarity and increase permeability.  This is added to the membrane transport model.

The MembranePlus permeability modeling platform has been utilized by companies across various industries and departments since 2014. MembranePlus has several primary applications:

Simulation of in vitro permeability & hepatocyte concentrations

  • Screen compound libraries and prioritize compounds for testing
  • Predict various permeability (e.g., paracellular, transcellular) & hepatocyte (e.g., diffusional clearance, lysosomal trapping, biliary excretion) processes
  • Estimate different intracellular concentrations, including:
    • Membrane
    • Cytosol
    • Lysosome
  • Assess impact of experimental variability on the predicted outcomes

Analysis of measured in vitro experimental data

  • Identify paracellular vs. transcellular permeability values
  • Calculate in vitro Km and Vmax for enzymes and transporters
  • Determine the impact of lysosomal trapping
  • Assess biliary excretion routes with sandwich hepatocyte assays
  • Fit parameters to build a robust model and unlock important insight from the data

The program provides several simulation modes to help you achieve your goals:

  • Single simulation – based on your drug properties (whether measured or predicted through ADMET Predictor) and permeability or hepatocyte experimental setup, easily run a simulation to predict the time course changes in concentrations (e.g., apical, basolateral, cellular or lysosomal).

  • Parameter sensitivity analysis (PSA) – during early drug development, researchers have a large number of compounds to evaluate and limited resources. With Parameter Sensitivity Analysis, quickly assess the impact of changes to certain properties (e.g., physicochemical or experimental) on critical endpoints. This can help guide your resource allocation plans and identify which permeability or hepatocyte experiments should be done next.

  • Batch mode – quickly screen a library of compounds based on predicted permeability or run the same compound through a series of different Caco-2, PAMPA, MDCK, or hepatocyte experiments. Easily prioritize compounds in any way you like: from high to low permeability, based upon potential issues with lysosomal trapping, etc.

Check out various case studies using MembranePlus and GastroPlus® by reviewing publications and webinars on our Resource Center.

Check out the exciting new features in MembranePlus v3! This version takes modeling of in vitro systems to the next level, allowing you to capture all relevant information from your experiments.

  • New Membrane models:
    • Modeling of diffusion through ex vivo skin samples – NEW!
      • Includes dermatomed skin, heat-separated epidermis, stratum corneum, full thickness
        skin, and simple membranes
    • Static and flowthrough diffusion cells
    • Modeling of complex topical formulations including solutions, suspensions, ointments,
      pastes, lotions, gels, and creams
    • Modeling of processes including evaporation, dissolution and precipitation, absorption
      into skin, diffusion and partitioning in skin and into receiver fluid
  • ADMET Predictor® Module:
    • Updated models from ADMET Predictor version 10.3
    • Prediction of Km/Vmax for metabolism by cytochrome P450 enzymes (CYPs), including
      isoforms 1A2, 2C9, 2C19, 2D6, and 3A4.
    • IVIVE settings for conversion to either intestinal cell monolayers or hepatocytes.
    •  Allow membrane model to be specified upon structure import.
    • New! Classification models to predict whether imported compounds are inhibitors or
      substrates for OATP1B3, OCT1, OCT2, OAT3, BSEP, and BCRP; as well as previous
      Pgp and OATP1B1 models.
    • Km values for OATP1B1, OATP1B3, OCT1, OCT2, OAT1, and OAT3.
  • New simulation outputs:
    • New outputs for all dermal related transport quantities like mass and concentration.
  • General features:
    • Bug fixes

View the full MembranePlus v3 release notes.

MembranePlus v3 is now available for download – instructions can be found here!

05. MembranePlus™ EXPERTS
Meet The Experts
06. Events
Upcoming Events
07. MembranePlus™ Resources
Scientific Posters