Many poorly soluble drugs may be delivered in dissolved form, either orally (e.g. in a liquid oral solution, soft gel, liquid filled capsule or semi-solid dosage form) or parenterally. However, it is very difficult to predict the solubility and stability of a novel API in a variety of excipient combinations and concentrations or how it might perform in vivo. As a result, successful manual design of formulations in such vehicles can involve elements of “art” and luck.
High-throughput systems. At TransForm, we have designed a series of high-throughput, formulation optimization platforms, and coupled them with advanced informatics, to enable our scientists to rapidly design and conduct thousands of formulation experiments on an API, and capture and mine the resulting data to identify non-obvious, potentially synergistic interactions between excipient combinations and the API. This enables our scientists to undertake a more systematic and comprehensive approach to formulating poorly soluble drugs, in acceptably-sized liquid or semi-solid vehicles, than has ever before been possible.
Using our FAST™ and SFinX™ high-throughput formulation discovery platforms, our scientists can rapidly and comprehensively characterize even small amounts of APIs with respect to:
|Simulated performance in vivo, and|
|Physical and chemical stability|
in a large number of different aqueous, semi-aqueous and non-aqueous vehicles, in various complex combinations and concentrations. We can run up to 5,000 parallel formulation experiments per week, using as little as 40µg of drug per experiment, in vehicle volumes as low as 7µl.
Systematic, informatics-driven approach. Informatics plays a key role in helping us design and run our experiments intelligently, to maximize the usefulness of the resulting data. In consultation with our partner, we design our experiments on its APIs to enable us to explore a broad experimental space while, at the same time, staying within excipient levels that are pharmaceutically acceptable for the intended use (e.g., animal dosing, GLP tox studies, first human dosing, etc.). We capture all experimental data automatically into a relational database, and then interrogate the results using proprietary data mining tools to glean insights into relationships between the API’s structure and its physical and chemical properties. This functionality enables us to learn from our experiments and rapidly design follow up experiments to further explore areas of promise, allowing us to work toward the desired formulation performance level in a stepwise and systematic fashion:
Broad applicability. Our iterative and systematic approach to liquid & semi-solid formulation design enables us to solve many difficult drug delivery problems for poorly soluble compounds, whether the goal is to find an acceptable formulation for human dosing or simply to obtain sufficient exposure for early animal or GLP tox studies. Our technologies also enable us to help our partners secure exceptionally broad intellectual property around preferred formulations.