Industry Insights with… David Fleet
Welcome to the latest blog in our Industry Insights series, where we ask our experts to share their in-depth expertise on topics within the pharmaceutical industry. Our Head of Formulation Development, David Fleet, has worked in the pharmaceutical industry for over 30 years and has extensive experience in developing drug formulations and preparing them for analysis and safety testing. In this blog, David discusses the key elements that are required for successful formulation development, from high quality formulation data to collaborative problem solving.
What is the primary aim of formulation development?
The main aim of formulation development is to design and test a safe, reproducible drug delivery system that matches the requirements of the client. For preclinical stages, which primarily involve safety studies, formulations are required that will maximise drug exposure to the test system and demonstrate a safe biological response. Whereas in clinical stages, the goal is drug efficacy and the development of a robust drug delivery system.
How important are pre-formulation studies for successful drug development?
Pre-formulation (or pre-clinical) studies are very important and can help to reduce risk during pharmaceutical development by supplying high quality data relating to the optimal physical form of the drug molecule. When you put yourself in the client’s shoes, they naturally want an efficiently designed formulation and/or drug delivery system that will accelerate their drug to the clinic. Having a strong understanding of the physicochemical properties of the drug substance and how they affect drug performance at the start can help significantly reduce the time and cost involved in developing a new pharmaceutical product.
How do you test formulations to ensure that they perform reliably and consistently while maximising exposure?
The support of our analytical team is vital when testing the performance of formulations, with assessing storage stability over time, compatibility with the packaging equipment and dosing equipment or analysing the response to extreme conditions. Stability testing provides important data relating to how the formulation changes over time and we assess a range of storage conditions that are defined in the International Council for Harmonisation (ICH) guidelines. Testing the robustness of the formulation involves subjecting the formulation to elevated temperature, pH, light and oxidation levels over a short period of time and then looking at the degradation profile following the exposure to stress. We may also assess the formulations microbiologically too.
Are there any specific technologies that are critical to your work?
Chromatography (especially HPLC) is a key technology that we use to separate mixtures into individual components, to identify degradants, related substances and impurities during drug product stability tests. At Arcinova, we utilise a range of chromatographic techniques, including gas chromatography (GC) (headspace or direct injection), ion chromatography, liquid chromatography (LC) and ultra-performance liquid chromatography (UPLC)-based methodologies.
Are there certain dosage forms that present particular challenges during formulation development?
Overcoming poor solubility and bioavailability remains one of the greatest challenges in formulation development. Beyond simply developing an aqueous solution, we also need to maintain its stability. For example, when developing a method for parenteral administration, either through injection, infusion or the subcutaneous route, the number of options is reduced as the formulation needs to be as physiologically compatible as possible. One of Arcinova’s strengths in this area is the ability to foresee these challenges and, once the structure is known, we can design a drug delivery vehicle that will mitigate the problem of poorly soluble drug substances.
How important is collaboration with other teams at Arcinova during formulation development?
Collaboration is critically important. Formulation development is just one stage in the process required to take a drug product to market. At Arcinova, all our services are supplied under one roof, and so we collaboration across all areas is easy. We pool our expertise and work together to solve problems. When challenges occur, it is often straightforward to find the right person within our facility with the knowledge and experience that relates directly to the situation, and we can quickly come together as a team to develop a new plan of action.
If you would like to find out more about the work of our Formulation Development team, please get in touch here