A number of separation techniques are used to obtain optically pure active pharmaceutical compounds. SARA Pharm Solutions offers the following programs to obtain an optically pure drug substance:
- separation of physical racemic mixtures via a reactive crystallization such as a salt formation process
- separation of racemic mixtures via chiral chromatography, employed for small-scale mixtures
In all the cases, the end product is fully characterized using structure elucidation techniques. In addition, we offer the possibility of growing a single crystal sample of the optically pure API, followed by its structure determination.
Crystal Structure Determination
At SARA Pharm Solutions we offer two distinct packages for crystal structure determination.
The packages consist of:
- single crystal analysis; we can grow a SC sample for you or take in your SC sample for analysis
- crystal structure determination from powder data; our scientists use computational tools associated with high quality XRPD data. This last type of analysis includes indexing and space group determination, intensity extraction, model(s) generation, crystal structure solving and refinement
SARA Pharm Solutions scientists have a high track record of solving the crystal structure of small molecules API.
Single Crystal Growth
A thorough understanding of solid form physchem properties is achieved through solving its crystal structure. For pharmaceutical customers that are interested in obtaining the crystal structure of the drug substance, SARA Pharm Solutions scientists have developed methods to successfully grow a single crystal (SC) sample followed by its SC data analysis.
Depending on the physchem properties of your drug substance we design the single crystal growth experiments.
Crystallization Process Optimization
We focus on obtaining a control over the crystallization process that can robustly yield the same crystalline form with the best yield and purity. We monitor the influence of the following key crystallization process parameters on the outcome of the crystallization process:
- stirring speed
- heating and cooling rates (incl. influence on MSZW)
- time and speed of anti-solvent addition
Additionally, we can provide information on:
- filtration time
- crystallization yield
- crystal habit and size
- drying process of the wet cake
Next to most applicable crystallization processes (cooling with and without seeding, anti-solvent addition) we investigate as well slow and fast evaporation, (anti-solvent) vapor diffusion onto solids and into solutions, hot-filtration, slurry, sonication and reflux.
With years of crystallization experience our scientists are able to provide a suitable solution to your crystallization process.
Crystallization Process Selection
In need of a robust crystallization process we offer the following options for an amorphous phase crystallization:
- salt or co-crystal formation
- free form solution crystallization (cooling, slow-evaporation, or anti-solvent addition)
- free form solvent mediated crystallization (slurry, or solvent-drop grinding)
- additional advanced crystallization processes
As regards the batch-to-batch variations our scientists focus on factors such as:
- purity profile
- crystal habit and size
The success of our crystallization programs are supported by our state-of-art HT-XRPD instrument ensuring a minimum analysis time for identification of crystalline phases.
Any robust crystallization process is easily transferred to 1L volume. A complete solid state properties evaluation is part of our scaling-up offer.