In vitro Permeation Testing (IVPT)
MedPharm offers its customers options for IVPT, including our unique MedFlux-HT® automated flow-through system or classic static cells.
IVPT is used to measure the permeation and penetration of a drug through tissue and is an essential tool for optimising topical and transdermal formulations. This is because a drug’s ability to permeate any tissue is very dependent on the quantity and quality of the excipients used. It cost-effectively provides a measure of performance of a product using human tissue and removes the uncertainty and ethics of working with ex vivo animal models.
MedPharm has spent many years perfecting procedures to minimise variation in this complex technique with a large number of potential variables. IVPT is often central to any bioequivalence justification for a topical generic product and regulatory authorities insist on a rigorous level of validation that can only be achieved after considerable experience.
IVPT is a cost-effective method used to demonstrate:
- The optimisation and characterisation of formulation performance
- De-risking clinical trial decisions
- Product performance to potential investors
- The bioequivalence of a generic compared to an originator product
- New marketing claims to educate key opinion leaders
MedPharm have four key methods for IVPT:
Classic Franz (static) cell
The classic static cell used for ex vivo permeation and penetration testing. They can be adapted to test diseased tissue biopsies.
Automated Flow-Through Cells
A unique flow-through method for ex vivo permeation and penetration testing. MedFlux-HT incorporates an automated higher throughput platform.
MedPharm’s unique ChubTur model is a static cell specific for measuring permeation and penetration through hard tissue such as nails.
Unique high throughput screen for measuring anti-microbiological activity through hard and soft tissue.
Static ‘Franz’ vertical diffusion cells are the industry standard for IVPT. MedPharm has also has created micro static cells to work with small pieces of tissue that may be more difficult to source such as:
- Healthy human skin, buccal and oesophageal tissue
- Psoriatic plaque biopsies
- Hyperkeratised skin
- Biological molecules
Measuring the permeation and penetration of a drug through nails and other hard tissues present specific challenges. MedPharm’s unique ChubTur model is a modified static cell specifically designed to measure the permeation and penetration of a drug through hard tissues such as nails. This proprietary validated model is widely accepted by regulatory authorities worldwide as the gold standard for modelling penetration through nails.
ChubTur® studies involving nails led to the first approval for demonstration of bioequivalence without the requirement of any clinical testing.
MedPharm has also developed a device called the TurSh™ which is used in combination with ChubTur® cells to explore the depth of permeation of drug substance within the nail.
Automated Flow-Through Cells
MedPharm has also developed an automated flow-through diffusion cell system MedFlux-HT® to more closely mimic the clinical situation. MedFlux-HT flows the receiver fluid under the tissue and then it is collected directly into 96 well plates. A robot works up the samples for direct injection in a quadpole LC-MS. A major advantage of this technique is that it prevents saturation of drugs with poor water solubility in the receiver fluid that can distort the results from static diffusion cells. The automation greatly improves the statistical variation.
Automated flow-through diffusion cells are useful for increasing accuracy in data from ex vivo permeation and penetration testing.
The significant benefits of MedFlux-HT:
- increased confidence in clinical performance, in particular, for lipophilic drugs
- increased opportunity to note patentable differences between formulations
- more credible evidence to support marketing claims
MedPharm has developed a unique high throughput screen, TurChub® to quickly differentiate the anti-microbiological activity performance of topical drugs or medicines through a variety of hard or soft tissues. A drug’s efficacy and ability to permeate across a nail or other hard tissue is measured by an adapted zone of inhibition measurement (the area of no growth of the organism). The assay provides rapid direct measurement of the activity of the drug below the tissue.
Data generated using the TurChub® model has been accepted by regulatory authorities as a substitute for clinical bio-equivalence data.
The TurChub method is both time and cost-effective as multiple drug types can be screened quickly simultaneously, therefore, decreasing development time during drug development.