The formulation of an active pharmaceutical ingredient (API) to ensure maximum bioavailability is central to successful drug development. When an API is insoluble or poorly soluble, it will require processing to ensure appropriate particle size and surface area to deliver on its pharmacokinetic profile, in a way that is both reproducible over multiple batches, and scalable for commercial use.
An effective, highly recognized method that offers a number of benefits in this area is nano milling, the process that reduces the particle size of an API in a liquid vehicle (typically aqueous) via grinding, using polymeric or ceramic media. The resulting liquid suspension can be filled into vials for injection or infusion, or tubes/bottles for topical or oral administration. It can also be sprayed onto particles and filled into capsules for oral use.
Starting at initial safety testing, APIs can be prepared at a small scale, in a non-GMP setting. Once safety testing is completed, that product can be used to provide proof-of-concept nano milling, to ensure the molecule’s compatibility for size reduction. Final GMP production for clinical supply is where the concepts of scalability and reproducibility truly become crucial, as larger quantities are manufactured.
The universality of nano milling (when compared to other formulation methods for poorly water-soluble APIs) is a major advantage. Nano milling has proven useful for APIs with solubility below 200 µg/mL, and it is also easily adapted for use with most insoluble APIs. Another advantage is that increased bioavailability means decreased dosage amounts, which may have a positive impact on potential adverse events.
Other advantages of nano milling include:
- No pH extremes or harsh organic solvents
- High API concentrations: 5-40+% API (w/w)
- Easy scale-up
- Efficient reproducibility
Altasciences has decades of experience developing nanosuspensions from scratch. We have on-site capabilities and a state-of-the-art equipment train, so we can quickly look at multiple formulations under accelerated conditions to choose the best one for GMP production. We can then move your project to our GMP suites and make your clinical supply. We also have the ability for complete analytical support at every step of the project, and additional integrated service offerings that can simplify the entire drug development process.
If you have an insoluble API, our experts in nano milling have the knowledge to advise you and support your development from initial development, all the way through to commercialization.
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