Dow appreciates that the solubility enhancement of a growing list of drug candidates in the pipeline is the leading challenge facing the pharmaceutical industry, and has developed technology to help address this. Bob Schmitt discusses his company’s uniquely tailored system and explains how it adapts to the varying needs of clients.
According to research by the Institute of Pharmacy at Nirma University, India, around 40% of all new chemical entities (NCEs) developed by drug companies are close to insoluble in water. To address this challenge, Dow has developed AFFINISOL, a solubilisation polymer portfolio, to ‘solve the insoluble’ – certainly an ambitious goal. But how does it work, and how are clients and the pharmaceutical industry responding? Bob Schmitt, an R&D fellow at Dow, explains.
What were the main challenges in developing the product?
Bob Schmitt: Cellulose chemistries are complex multistep reactions that require significant energies to tailor the polymer for this application. In order to develop an extrudable grade of hydroxypropyl methylcellulose (HPMC), we needed to use a chemistry that resides outside of the current USP space while still maintaining generally recognised as safe (GRAS) status. And the ability to tailor the chemistry to the application has enabled development of a polymer tailored to this specific application, optimising the processing and formulation performance.
Why does Dow think that solubilisation of poorly soluble drug candidates is the leading challenge facing the pharmaceutical industry?
Interactions with our customers in Europe and across the world indicate that they are increasingly working with active pharmaceutical ingredients (APIs) with low solubility. This means there’s a lot of demand for polymers that can enhance the solubility of these compounds via formation of amorphous solid dispersions, which is where AFFINISOL becomes very useful.
How does it work?
We are focused on optimising products for solubility enhancement, which improves the product and the process performance. For example, hypromellose acetate succinate (HPMCAS) is known to be an excellent polymer for the formation of a stable amorphous API, which happens via spray drying and also helps minimise recrystallisation in the gastrointestinal tract.
In order to optimise formulation performance, we have offered tailored substitutions to match the performance needs of specific APIs. This is coupled with polymers that demonstrate reduced apparent viscosity in the spray solution in order to increase the performance of the spray-drying process. The consequence of this is products that are optimised over several performance metrics.
How do you ensure a robust formulation with your approach?
Dow’s approach employs a quality-by-design (QbD) sample set that allows formulators to explore the polymer-design space in early development and ensures robust performance of the formulation.
What sets your approach apart from the competition?
Each API to reach the clinic is unique and extremely valuable. We have invested in a full range of polymer capabilities starting with high-throughput research through a current good manufacturing practice (cGMP) market development plant. These capabilities allow us to work closely with customers to insure they are provided with the optimum polymer for their API, the dosage form of their choice, and the processing technology they require.
What has been the feedback from clients so far?
We have received very positive feedback from our clients to date, and there has been great interest in our AFFINISOL HPMC HME material designed for the hot melt extrusion processing of poorly soluble drugs. This product is under evaluation at a number of locations, and we anticipate it will move into late-stage clinical trials in 2015.
One surprise from the market has been the strong desire to conduct QbD studies on a clinical scale. Our cGMP market-development plant has been an ideal asset to support this work as it provides a sample set that covers a robust design space, which can be easily processed within clinical-scale equipment.
What are the implications of your new approach for the wider industry?
Our goal has been to expand the number of excipient options available for solubility enhancement, while at the same time proactively supporting QbD product development. We believe this approach maximises the clinical success of each API.