4. Performance testing – In vitro & EX VIVO models for percutaneous absorption

RaDes established a range of powerful in vitro and ex vivo models for de-risking dermal development projects and to assess the quality and performance of topical products. These models provide support through the entire lifecycle of a drug product from compound and formulation selection to bioequivalence testing and post-approval changes. High-performance analytical equipment is in place for selective and sensitive analysis.

In vitro release test (IVRT) using vertical diffusion cells
  • Determination of in vitro drug release rate through an artificial membrane
  • Ranking and selection of formulation prototypes for dermal or transdermal application
  • Evaluation of equivalence of topical products for generic submissions as required according to the “EMA Draft guideline on quality and equivalence of topical products”
  • Scale-up and post approval changes (according to FDA’s SUPACC SS)
  • Support from initial assessment up to fully validated methods according to OECD, FDA, or EMA, including analytical method validation according ICH guidelines.
  • Robotic diffusion system with dry-heat blocks and optimized stirring to obtain superior data quality. 12 parallel vertical diffusion cells in place
  • For introduction and examples on IVRT see RaDes webinar recording here (YouTube).
In vitro permeation test (IVPT) using vertical diffusion cells
  • Evaluation of the characteristic permeation profile of the drug/ingredient(flux rate & permeated amount) through animal or human skin
  • Lead compound and formulation prototype selection to de-risk clinical program
  • Bioequivalence (BE) studies for topical generic development according to EMA “Draft guideline on quality and equivalence of topical products”
  • Absorption studies for safety of chemicals, pesticides etc. according OECD 428
  • In vitro dermal absorption studies of cosmetic / consumer products according to Scientific Committee on Consumer Safety (SCCS) guidance document
  • Scale-up and post-approval changes (SUPAC SS)
  • Support from initial assessment up to fully validated methods according to OECD, FDA, or EMA, including analytical method validation according to ICH guidelines.
  • Investigation of distribution between epidermis and dermis (heat splitting)
  • Inhouse preparation of pig ear skin samples established to use fresh pig skin in IVPT studies on demand
  • Optionally, use of Strat-M® artificial, non-animal-based membrane as screening tool for skin permeation of topical formulations and for transdermal patches
  • Robotic diffusion system with dry-heat blocks and optimized stirring to obtain superior data quality. 12 parallel vertical diffusion cells in place
Ex vivo skin penetration model (Hamburg model)
  • Skin penetration model using viable pig ear skin. Excellent correlation with human skin demonstrated
  • Allows determination of cutaneous biodistribution of topically applied drugs
  • Penetration profile into different skin layers. Direct determination of actives concentration at the site of action possible.
  • Cost effective and without ethical implications
  • In cooperation with university hospital Hamburg Eppendorf (UKE). Analytical method development, sample preparation and analysis at RaDes
Skin Pampa
  • Screening tool for dermal permeation potential
  • 96-well plate format using a porous lipid-impregnated filter to mimic the stratum corneum as the main barrier for dermal absorption
  • Allows comparison of topical and transdermal formulations to support ranking & selection
Nail penetration model

The nail is a barrier fundamentally different to the skin and requires different formulation approaches and penetration models

 

  • Inhouse developed model using human nail clippings to determine the API amount penetrated into the nail plate
  • As nail swelling facilitates penetration, formulations can also be characterized with regards to their nail swelling capacity
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