Case objective

Polymorphs are critical in pharmaceutical development because different crystal forms of a drug can affect its solubility, stability, bioavailability and manufacturability. Choosing the right polymorph helps ensure consistent drug performance and regulatory compliance. Nuvisan´s team of experts in the field of solid forms was approached by a client to tackle the challenge of constantly producing desired form B of an active pharmaceutical ingredient (API).

 

Our approach and findings

A polymorph screening was performed to demonstrate that polymorph B was the more stable form. A crystallisation process with seeding was then developed to improve the robustness of the process. As the XRPD pattern of both polymorphs were closed, we developed a correlation plot to ensure polymorph B identification. An X-ray powder diffraction (XRPD) analysis was developed and validated to support API release for clinical studies and 2 kg batches were produced under good manufacturing practice (GMP).

 

 

Our XRPD D6 Phaser is an X-ray powder diffractometer used to analyse the crystalline structure, phase composition and crystallinity of solid materials. Selecting the appropriate polymorph helps ensure performance and stability.

 

 

Optimised crystal structure

 

Our case-specific key technologies

Polymorph screening	Polymorphism studies to optimise the solid-state properties of your APIs and formulations Our expertise helps ensure improved solubility, stability and manufacturability.
Seed production	Synthesis, from milligrams to hundreds of grams
Process development	State-of-the art laboratories for a fast and efficient route evaluation, selection and scale-up for all kinds of chemistries
Scale-up and GMP production	Flexible scale: from gram to kilogram scale, bridging the gap between CRO and CMO Infrastructure optimised to support process development from milligram to kilogram GMP-compliant Ability to handle highly potent active pharmaceutical ingredient (HPAPI) up to occupational exposure limit (OEL) 0.1 µg/m3, cytotoxic, antibiotic and controlled substances.
XRPD testing	2 XRPD instruments, including one that is qualified under GMP standards.

 

Facing similar challenges? This is how Nuvisan´s team of experts in the field of solid forms can help

Nuvisan´s highly experienced scientists were available to assist in selecting and controlling the solid state of the API. They conducted solid-state investigations to identify polymorphs and to support seeding point determination. This study provided a deep understanding of the solid state of the API, enabling improvements in the manufacturing process for smoother scale-up.

Our services included:

• Polymorph screening to determine the more stable polymorph
• Manufacturing of a 100 g batch of polymorph B to be used as seeds under non-GMP or GMP
• Development of a crystallisation process with seeding and slow cooling to obtain polymorph B
• Upscaling from gram scale to kilogram scale
• Development of a XRPD analytical methods and plot to monitor polymorph B manufacture
• Validation of XRPD analytical method for GMP release testing
• Manufacturing of 2 kg batches of API in GMP environment
• Release of API batches with targeted polymorph.

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