Complex Purification and Chiral Resolution Development
Purification and chiral resolution are critical steps when developing a synthetic process, directly impacting the yield, quality and cost of the final product.
At Enantia, we apply our know-how in solid-state chemistry and crystallization development to design and implement scalable purification processes. This ensures optimal results while minimizing the final process’ costs and time.
The strategy is based in finding new crystalline forms like salts and cocrystals for the target compound. Then, we evaluate their purification capacity in your crude, and use them to develop a crystallization or slurry step. This results in a process that yields the required purity and can be easily implemented at larger scales. After that, form dissociation and coformer and counterion recycling are also studied at Enantia to ensure the maximum efficiency.
For resolution steps we follow the same principles by using diastereomeric salts and cocrystals. This allows us to develop scalable chiral resolution processes, which are key when working with asymmetric compounds and racemic mixtures.
If you are exploring second generation process to increase efficiency and reduce costs, or if you are facing a challenging purification, contact us to leverage our know-how in crystalline solid forms.
Chiral Resolution
One of the most significant benefits of our cocrystal technology is its ability to achieve chiral resolution, a process that separates enantiomers to obtain the desired pure chiral form. This is especially useful for compounds that are difficult to resolve using traditional methods like diastereomeric salt formation. By using cocrystallization with enantiomerically pure coformers, Enantia’s cocrystal technology ensures superior purity and enantiomeric excess, minimizing the risk of impurities and improving the overall quality of your final product.
This method allows for the efficient separation of enantiomers, ensuring that only the desired chiral form is present. This is crucial in the pharmaceutical industry, where the purity of each enantiomer can have a significant impact on a drug’s safety, efficacy, and regulatory approval. Our cocrystal technology offers a more reliable, cost-effective solution compared to chromatographic methods, which can be both expensive and time-consuming.
Purification
Salts and cocrystals provide a cost-effective alternative to traditional purification techniques, such as chromatography. While chromatography is often the go-to solution for separating compounds at early-stage, it is both costly and time-consuming. In contrast, crystallization, specifically through the use of salts, cocrystal and solvates is a simpler, more efficient method that can be scaled up effectively for large quantities of material.
Enantia’s expertise in solid-state is key to identify crystalline forms to purify your crude, and, even when the traditional crystallization methods through salt formation are not an option, our cocrystal technology remains useful.
The result is a scalable and optimized process to obtain the desired product with exceptional purity, even in cases where other methods fail.
When must cocrystals be specially considered to purify and resolve?
While salts are very useful to purify and resolve, cocrystals have recently emerged as a game-changing tool in process chemistry. Cocrystals offer significant advantages over traditional techniques, especially when other options fall short, such as when a low melting point or a non-ionizable molecule is hard to crystallize.
There are several instances where cocrystals are particularly effective in resolving complex purification and resolution challenges:
- There are no other crystalline forms (free base or salts) allowing purification or resolution.
- Salt formation is not an option because the compound is non-ionizable.
- The known crystalline forms (usually salts) do not provide a selective enough purification or resolution.
- The best crystalline forms are protected by intellectual property rights.