Case Study: Polymorph Screening And Control

When active pharmaceutical ingredients (APIs) are produced in multiple lots, it is possible for inconsistencies to develop in the quality (i.e. physical and chemical properties) of the drug substance. A major pharmaceutical company came to SSCI, A Division of Aptuit, when confronted with such a problem. The problem arose in the manufacture of the API for an antibiotic drug product that had been on the market for more than twenty years.

A third-party contract manufacturer was responsible for the production of the client's API. Problems with the flow properties of the drug substance were encountered during the manufacturing of different lots using the same process. Similar crystal morphologies were obtained from the different lots, and x-ray powder diffraction (XRPD) analysis indicated the same form was presented in all lots. However, a large number of fine particles were observed in the problem lots.

The polymorph screening and crystallization process control done by Aptuit clearly identified the flaw in the development process that was resulting in poor lot-to-lot API quality. SSCI scientists were able to demonstrate that the client in fact had multiple API forms instead of one, and that the crystallization process being used by the client's API supplier was inefficient in forming only the desired product. Aptuit provided a manufacturing solution that resulted in clear efficiencies, which translated to less waste, reduced cost and improved production time.