MedPharm has developed a number of proprietary in vitro and ex vivo models to help test the efficacy of formulations. These models take the testing process a step further than traditional permeation and penetration studies and provide a better indication of how developed formulations may perform in the clinic.
MedPharm’s efficacy models are recognised by the regulatory authorities, and have been used to demonstrate the in vitro “sameness” of a generic formulation without the need for a clinical trial; the first instance of its kind. These models are designed and validated with various tissues to assist:
- API selection
- Formulation optimisation and selection
- Dosage optimisation
- Formulation retention assessment
- Relative efficacy assessment
- Equivalence testing
- Technology validation
- Claim support; product quality and performance
Fungal Infection Model
Formulations can be applied to human tissue and infected with dermatophytes such as Trichophyton rubrum or Trichophyton mentagrophytes or alternative fungi and yeasts such as C. albicans to replicate topical and nail infections, allowing the efficacy testing of antimicrobial and antifungal formulations. Their relative efficacy can be compared using conventional microbiological methods or bioassays in order to select the best formulation and dosing regimen for clinical evaluation.
Propionibacterium acnes and Staphylococcus species are the major commensal organisms usually resident in the pilosebaceous glands of human skin. P.Acnes in particular is implicated in the pathogenesis of acne vulgaris. MedPharm has developed its own method, in-house, to assess the efficacy of anti-acne formulations by isolating sub-surface bacteria from large areas of skin.
Bacterial Infection Model
In MedPharm’s bacterial infection model, tissue sections are initially infected with S. aureus (or another appropriate organism) and then mounted in a proprietary ChubTur® cell. The receptor compartment of the ChubTur cell contains a humidity control medium that ensures the microorganisms viability. The formulation applied on the skin surface is incubated according to the microorganism requirements and the performance of the formulation is determined by removing the tissue sample after treatment and recovering any remaining viable microorganism, using a previously validated bioluminescence ATP assay.
Infection models include infected wound (infected epidermal layer), infected skin (infected dermal layer) and infected nail models. These diseased-tissue models also allow replication of the tissues’ permeability characteristics, so flux of a formulation through diseased skin can be established to enable optimisation and selection.
Barrier Models Against Pathogens
MedPharm has developed models to show the prophylactic or protective anti-microbial properties of a test compound against invading topical pathogens including bacteria, yeast, fungi, moulds, and bacteriophage (as a surrogate for viral contact).
Skin Inflammation Models
Inflammation can be induced in skin equivalent models (such as stimulated keratinocytes) and human skin by using cytokines including IFN-γ, IL-1α, IL-1β, TNFα . The responses of the tissue can be measured via inflammation markers and the model can then be used to investigate the relative efficacies of drugs and/or formulation for the treatment of inflammatory skin diseases e.g. psoriasis, AD etc.
Other Efficacy Models offered by MedPharm
- Mucociliary clearance and mucoadhesion
- Sebum and sweat production
- Viral disease models