>>Crystallization Method Development

Solid form control

Almost all APIs are crystallized at some stage in their preparation, and many are formulated into drug product as crystalline materials. Traditionally, API crystallization processes were optimized primarily around reactor throughput and chemical yield. Unless problems were encountered in product recovery or downstream use, consistency of solid form was often ignored.

It is now understood that a crystalline API needs to exhibit consistent physical properties when made at each stage of the development process (gram to multi-kilogram scales). In so doing formulation-development problems are minimized and regulatory requirements are met. Triclinic is experienced in generation of crystallization methods, including the background information necessary to impart solid form control (polymorphic form, particle size, etc).

Chiral Crystallization and Resolution

Much of Dr. Stahly's career was spent in the area of chiral chemistry, predominantly in generation of enantiomerically pure materials. While asymmetric synthesis is being used commercially, diastereomeric salt crystallization remains the industrial workhorse for production of pure enantiomers. An understanding of solid-state chemistry is crucial for planning, developing, and troubleshooting crystallization-based resolution processes.

Generation of the binary phase diagram of a racemic mixture, either experimentally or by calculation, is a critical first step in planning a resolution. Triclinic can guide you through an understanding of the solid-state chemistry of racemates and enantiomers, collection of necessary background information, selection of the appropriate resolution method, and generation of a robust process.

Solid-form Scale Up

Triclinic has the ability to provide your solid-form API of choice in kilo-scale batches. The material is suitable for pre-clinical development including excipient compatibility testing. We are also able to work with your API manufacturer of choice in order to maintain control and consistency which is often lacking. Instead of repeated attempts at producing the selected form using random chemical processes and conditions, Triclinic identifies the nucleation event and develops a process to control it - leading to consistency and predictability lot-to-lot. Contact us for a comprehensive disucssion on how we can aid your critical scale-up step as you progress int he develoment process.