Reckitt Benckiser scientists came to MedPharm with a challenge: can we devise models to determine how well their flurbiprofen throat spray and lozenge permeate the drug in the human pharynx? In response, the MedPharm team developed clinically relevant in vitro models and incorporated them into a study to test the permeation of each flurbiprofen formulation. Our product development team used ex vivo pharynx tissue from pigs and the team used ex vivo pharynx tissue from human cadavers for the full experiment.
MedPharm’s findings demonstrated that the permeation of flurbiprofen from the two formulations was the same. These data also supported the calculation of a clinically relevant dose for the non-steroidal anti-inflammatory drug. These findings were later published at the 3rd German Pharm-Tox Summit in Germany, 2018 and used to educate key opinion leaders on the equivalence of Reckitt Benckiser’s formulations.
Sandoz produce a 5% Tavaborole topical solution to treat onychomycosis (T. rubrum), which is a fungus that infects nails. T. rubrum discolors nails it has infected and can make them painful to touch or cut. This topical solution provides an important alternative for patients where oral antifungal medications may have unwelcome side effects.
Sandoz wanted to understand the impact of nail varnish on the efficacy of its solution.
To address this, MedPharm designed a study using its proprietary TurChub model. This model is especially designed to quickly differentiate the anti-microbiological activity performance of topical drugs or medicines through a variety of hard or soft tissues. It can provide a rapid and visual read out of the efficacy of a treatment and has been rigorously validated to be representative of the clinical situation.
A specialty pharmaceutical company requested MedPharm scientists to investigate a 5% cream formulation of a proprietary drug to see if the relatively high loading of the drug could be reduced. The aim was to achieve this without significantly changing the formulation’s excipients.
The MedPharm team went back to first principles and measured the solubility and stability of the active in the different excipients in the formulation. They showed that by adjusting the concentration of the excipients in the existing formulation to optimise the drug’s thermodynamic activity they could achieve the same penetration and permeation in IVPT experiments with a 3.75% cream. This reduction benefits patients by reducing their total exposure to the drug and significantly reduced the cost of manufacture of the product.
The activity of the 3.75% cream was subsequently demonstrated in the clinic in a Phase 3 trial by the client.
MedPharm’s specialist tissue biologists have developed a range of in vitro activity models for measuring the pharmacokinetics and pharmacodynamics of topical products applied to the skin and other human epithelial tissues. These models don’t only measure the penetration and permeation of the active through the skin but also demonstrate that the active ingredient is positively impacting relevant disease-related pathways that have been upregulated.
The question remains how representative are these models to the clinical environment? No matter how good a model is it is still a model and there remains a level of uncertainty. To test for a correlation MedPharm scientists reviewed the data from clinical studies reported in the open literature on atopic dermatitis and found that the upregulation of key inflammatory pathways (IL13 and IL31) was in the same order of magnitude as those found in the MedPharm in vitro models. This gives clients and their potential investors an extra level of confidence that the activity seen by their potential products in the models will be reproduced in the clinic.
Pfizer’s Crisaborole ointment, 2% (Eucrisa) for atopic dermatitis is commonly applied by patients in combination with emollients. MedPharm designed and performed a study to determine the potential effect of emollient application on Eucrisa performance.
MedPharm used its proprietary MedFlux-HT® automated flow system to determine the penetration of Eucrisa through fresh human skin in the presence and absence of these emollients.
MedFlux-HT closely replicated a clinical environment for the study, preventing any drug saturation issues seen in static models. The system used automation to generate more data with less variability, providing greater confidence in the study results. This IVPT model was more cost-effective, sensitive and less risky than running a clinical trial to monitor the same effects.
