SubscribeProcess research and development involves more than just finding the right synthesis route. The crystallization of the API or intermediate products in the most appropriate solvent system is just as significant.
The synthesis method and knowledge of crystallization behavior positively influence the yield and purity of the product. As an independent firm with extensive experience in the pharmaceutical industry and wide-ranging technological expertise, Solvias is your preferred partner for challenging synthesis and crystallization projects.
A Project Success Story
Our development of a new synthesis method for doxorubicin, a cytotoxic antineoplastic drug used in chemotherapy, is just one example of Solvias' successful work on behalf of a client. By implementing our expertise in the areas of polymorphism and the synthesis of active ingredients, we delivered the desired results. In Phase 1 our expertise in crystallization and polymorphism was of critical importance. In Phase 2 we developed a cutting edge, robust, economical, and ecological method. Based on our experience in process R&D - particularly in the development of complex molecules for pharmaceutical research - we easily and success-fully accomplished these tasks.
Phase 1: Purification of Daunorubicin
Daunorubicin is produced through a fermenta-tion process that generates a crude product with a purity ranging from 30 to 35%.
In addition to waste products, the fermentation process also generates three by-products from the raw material. The purification of daunoru-bicin is performed in two steps. First, the reac-
tant is concentrated, and then purified through a crystallization process. Next, a solvent screen-ing was conducted in order to find the most appropriate dissolution agent.
Figure 1: The individual project phases
We obtained the required daunorubicin with a purity of 95% and a yield of 90%. These results were successfully reproduced on a larger scale.
Phase 2: Optimization of Synthesis Process
In this phase the complexity of the reactant, combined with its acidic lability, presented a challenge. Therefore, it was necessary to pain-stakingly select individual synthesis operations. Ultimately, we optimized the synthesis process such that each step had a yield of over 90% as well as a good space-time yield. This phase can also be processed on a multi-gram scale.
Phase 3: Isolation of Doxorubicin
In this phase it was necessary to optimize the isolation of the product from the reaction mix-ture. This task was particularly demanding due to the hydrophilic properties of the product. Nevertheless, this problem was solved in col-laboration with our clients.
Through efficient project management, we brought the entire process to a rapid and suc-cessful conclusion, including the time-sensitive Phase 2. The project manager regularly provid-ed the client with progress reports, and ex-changed information and expertise. The results were fully documented, and the information was provided to our customer. On the basis of this documentation the client could success-fully produce doxorubicin.