Stephie Lee, M.S.
Stephie Lee, M.S., is a Scientist at Catalent’s San Diego facility. That site focuses on development and analytical services. She has a broad background in preclinical and clinical formulation, process development and GMP manufacturing of small molecule candidates, with a focus on early phase strategies for bioavailability enhancement of poorly soluble compounds.
Stephie has managed more than 60 oral formulation programs, including spray dried dispersion, fluid bed processing, and micronization projects.
Prior to joining Catalent, Stephie was a researcher at the University of California, Los Angeles (UCLA), where she focused her research on the effects of various reaction conditions on the morphologies of nano conductive polymers. Stephie received her Master of Science in Chemistry and her Bachelor of Science in Biochemistry from UCLA.
Get to know this Catalyst in drug development. Learn what drives her commitment to researching solubility issues, access her works on early phase development techniques, best solvents for spray drying and hear her best practices for GLP Toxicology Studies.
Key Expertise: Early Phase Development, Bioavailability Enhancement Technology
Connect with Stephie Lee on LinkedIn
A CONVERSATION WITH STEPHIE LEE
Your work has involved a good deal of early phase formulation development. How does early phase development differ from late phase development?
Early phase development has very different goals than late phase development. For an early phase program, the developed formulation is used in clinical trials for obtaining safety and efficacy data. By contrast, the focus of late stage development would be to develop a robust formulation and thoroughly understand the performance of the formulation. Most of the time, clients with new chemical entities (NCEs) come to Catalent with limited funding, resources, API, and time. These NCEs often pose physicochemical and biological challenges. Understanding the goals for early phase development allows us to take an agnostic approach to identify the best technology for overcoming these challenges and focus on developing practical formulations to get these NCEs to patients under condensed timelines.
For solubility-limited molecules, what formulations would best support a successful GLP toxicology study?
It is key for a GLP formulation to provide enough exposure in the selected animal models to achieve toxicity. For molecules exhibiting solubility challenges, a simple solution or suspension formulation will unlikely do the job. If the molecules are not soluble or they precipitate in the gastrointestinal tract, they cannot be absorbed, and the bioavailability could plateau even if higher doses are administered. An enhanced formulation will therefore be needed. An amorphous dispersion, either a spray dried dispersion or a hot melt extrusion, can be a good option for these solubility-limited molecules. Amorphous dispersions can overcome the thermodynamic solubility by achieving a transitory supersaturation state and hence allowing the molecules potentially get absorbed at this supersaturation state. These amorphous dispersions can be dosed as suspensions in GLP tox studies and efforts to develop a more sophisticated, finished dosage form to support clinical studies can then be made in parallel to the GLP tox studies to shorten the overall development timelines.
How can Catalent’s technology help overcome solubility challenges?
Catalent is one of the industry leaders in solubility and bioavailability enhancement technologies – spray drying, hot melt extrusion, micronization, lipid, etc. Catalent takes a holistic approach looking at all contributing factors – physicochemical properties of the molecule, phase of the program (preclinical, GLP, Phase I/II/III, commercial), patient population, timelines, etc. before providing strategic guidance to our clients on developing a “fit-for-purpose” formulation.
What do you believe are the best solvents for spray drying?
In general, suitable solvents for spray drying should possess relatively low boiling points, provide adequate solubility and stability for the molecules to be sprayed, and be easily dried in the spray dried dispersion products to meet USP <467> requirements for residual solvents. The best solvents are acetone, ethyl acetate, ethanol, and isopropanol which are Class 3 residual solvents (per USP <467>) with low toxicity and pose low risk to patient health. However, a lot of molecules with poor aqueous solubility often have low solubility in these solvents as well. More aggressive solvents such as methanol, dichloromethane, and tetrahydrofuran (Class 2 residual solvents per USP <467>) will need to be incorporated to dissolve these molecules in the first place for spray drying. The synergistic effects of solvents on solubility can be hard to predict so a systematic screening approach should be taken. It is crucial to ensure secondary drying is effective in reducing the residual solvents contents to meet the limits outlined in USP <467>.
As a woman in science, what is the biggest challenge you face?
When I first started in the industry, it was difficult for me to identify myself as a young female scientist. I struggled with the double-bind dilemma for women – to be feminine or to be competent. I felt that to prove myself, and get recognized, I had to act as mature and nonfeminine as possible. Fortunately, there are a lot of great female scientists and leaders at Catalent who continue to mentor me and show me how to be confident in my abilities without having to disguise my true self. We as women can bring different perspectives to problem solving and make impactful contributions. I learned that no matter what happens, I should always keep my focus on what is most important and that is doing great science.
ACCESS STEPHIE LEE’S WEBINARS, PRESENTATIONS AND WHITE PAPERS
- Solvents, Polymers & Cyclones – Bioavailability Enhancement through Spray Dried Dispersions, Xtalks Webinar
- Strategy Design & Formulation Considerations for GLP Toxicology Studies, Xtalks Webinar
- The Importance of Formulation Design in Oral GLP Toxicology Studies, Pharmaceutical Outsourcing
- Formulating a plan for toxicology studies, EPM Magazine