The road to drug approval is littered with challenges, such as tight timelines, spiraling costs, and, of course, the need to demonstrate efficacy and safety. Bioavailability is often overlooked. However, if it is enhanced, it can benefit both patients and healthcare organizations.
When a patient takes a tablet, it disintegrates to release the active pharmaceutical ingredient (API). Once dissolved, the API goes on a long journey. To begin, it must dissolve in the gastrointestinal tract before it can be absorbed through the gut wall. Next, the API enters the blood and passes through the liver.
Finally, when it reaches the systemic circulation, it travels to wherever it’s needed in the body. Along the way, some of the API is lost. Bioavailability is the proportion of the administered dose that reaches the systemic circulation and is available to have the desired effect.
Although intravenous administration results in almost 100% bioavailability, oral drug products are preferred due to their better physical and chemical stability, and higher patient compliance. Achieving high bioavailability for orally administered drugs is difficult. In fact, almost half of the drugs that are currently in development are classed as ‘practically insoluble’.
Many barriers prevent high drug bioavailability. They can be split into two categories: features of the human body, including certain disorders, genetics, and an individual’s level of physical activity; and drug product-related factors, such as the administration route, physicochemical properties of the drug substance, and the type and composition of the drug product.
Where to look for help when enhancing drug bioavailability?
To find out how investing in formulation strategy could help biotechs to overcome these challenges, I spoke with Lien Saerens, Pharmaceutical Development Manager at Eurofins CDMO, about the company, its technology, and its Highway to Clinic strategy.
Eurofins CDMO has four key qualities. First, it forms partnerships with biotechs to take a drug substance from an early stage of development all the way to the market. Second, it adapts to the requirements of each project.
Third, the company has internal capacities for development, manufacturing, packaging, and logistics, meaning it offers a full package to support clinical trials. And fourth, Eurofins CDMO carries out a feasibility assessment at the beginning of each proposal, so that it can have confidence in any project it takes on.
Eurofins CDMO has several strategies to help biotechs bring drug products to the clinic, but it’s the Highway to Clinic strategy that focuses on bioavailability.
“It’s a fast track for drug development, which focuses on those poorly soluble new chemical entities,” Lien told me. “It also covers a wide range of activities, such as complete analytical support and method development, drug substance characterization, pre-formulation studies, and stability studies on the drug products that have been developed.”
How is bioavailability enhanced, and what challenges can be overcome?
The Highway to Clinic strategy enhances drug product bioavailability, but it is also flexible and can overcome other challenges. For example, Eurofins CDMO recently adapted to meet one of their partner’s requirements for high dosing.
To do this, they performed supersaturation studies to maximize the amount of API in their drug product concepts. “A supersaturated state can be a driving force for more absorption of a drug product in the body,” Lien explained.
By combining certain polymers and surfactants, the Eurofins CDMO team was able to maintain the API at a 20-fold higher solubility. Two drug product concepts were selected, underwent further development and testing, then sent to the partner company for a pharmacokinetic study, During the study, a big improvement in bioavailability was observed. Moving forward, Eurofins CDMO and the partner company will refine the drug product concepts before entering the clinic next year.
On another occasion, Lien told me that the Highway to Clinic strategy had helped a company to enhance the bioavailability of its veterinary product despite having less than five grams of API to work with. Eurofins CDMO performed solubility tests and discovered that the drug substance was very insoluble.
This prompted them to screen for nanosuspensions and, after further processing and careful selection, four drug product concepts were chosen. These underwent stability and stress testing before a single formulation was taken forward to a pre-scheduled pharmacokinetic study.
“This all occurred in quite a short timeframe, in two to three months. When the customer conducted the pharmacokinetic study, they noticed a significant increase in bioavailability,” Lien said.
What can we expect in the future?
In the future, the need for both small biotechs and big pharma to enhance the bioavailability of their drug products will only grow. “Companies have databases of molecules from which they select the best candidate, but the tendency we see is that more and more of these are poorly soluble,” Lien told me.
Additionally, Lien thinks that the technology that is available is constantly improving, which means companies should be excited by the prospect of investing in their formulation strategy.
Eurofins CDMO’s Highway to Clinic strategy supports companies to overcome various challenges on the road to drug approval. For biotechs, it can help to demonstrate a proof of concept that will allow them to secure further funding and, hopefully, reach the market.
For patients, it could provide them with access to more effective oral treatments that are also less expensive for healthcare organizations than parenteral delivery.
To find out more about Eurofins CDMO and its Highway to Clinic strategy, click here to watch the ‘Highway to Clinic: Formulation strategies for improved bioavailability’ webinar.