API Purification Methods: Do You Know How To Pick the Best One?

Below we outline the key methods we utilize to ensure the most effective purification strategy.

Posted: March 3, 2016

API Manufacturing and Pharmaceutical Manufacturing

At PCI Synthesis, we are committed to quality control throughout every aspect of our operations. Critical to the quality of our NCEs, generic APIs and custom chemicals is the assurance of proper purification processes.

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DSC_9739The most common and effective way we purify solids at PCI Synthesis is by crystallization. This involves finding a solvent where the solid to be purified has low solubility at room temperature but is very soluble in the solvent at elevated temperatures. The solid is dissolved in the solvent at the boiling temperature and is allowed to cool so that the compound crystallizes out of the solvent in pure form and the impurities stay in the solution (also known as mother liquor). This process is often repeated until the desired purity is reached. Many times a single crystallization can provide pure compounds of greater than 99% purity. If a solid is too soluble at room temperature in a chosen solvent then a mixed solvent system is used whereby another solvent (anti-solvent) is added to the system. For example, the purification of amine salts can be accomplished with a mixed system of both an alcohol and an ether solvent used at the same time. The salt is first dissolved in the least amount of alcohol as possible. Then the ether solvent is added slowly until the salt begins to precipitate out of the solution, since the salt is insoluble in the ether solvent If crystallization cannot be used then another less effective option we employ is trituration. This involves “washing” the solid with a solvent (either hot or at room temperature) in which the compound is not soluble in, but in which the impurities are soluble to a much greater degree. Repeated “washing” or trituration can be used to enrich the purity of a solid.

For compounds which are liquids or oils, we purify them either by distillation or with chromatography. If a liquid is volatile enough the best approach is by distillation. Compounds that are too high-boiling are purified by column chromatography; the most common being silica gel chromatography. Other types of chromatography can be employed, such as alumina or reverse-phase chromatography. Automated systems (Biotage and Teledyne-Isco) are also used on occasion which greatly ease the purification process. Many times compounds are purified by preparative HPLC instruments using either normal phase (silica gel) or reverse-phase columns.

PCI is well-experienced in adopting the right purification process for each project we undertake. This is just one more facet to our commitment to quality in our commercial and developmental scale manufacturing activities for life sciences companies around the world.

About the Author

Ed Price CEO of PCI Synthesis
Ed is the President and CEO of PCI Synthesis (PCI), he serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA).

Do you have questions? Talk to Ed.