Pharmaceutical API development

Malvern Panalytical has a deep understanding of how to apply physicochemical analysis throughout the lifecycle of your API, from discovery, through scale-up and all the way to manufacturing. Our systems can help you answer questions about API bioavailability, stability, processability, and quality. They support:

• Selection of viable candidates
• Understanding of critical material attributes (CMAs) 
• Optimizing scale-up processes in API manufacturing
• Application of Quality by Design (QbD) by helping define the physicochemical design space 

Many APIs fail on scale-up due to issues with stability and/or processability. Malvern Panalytical systems provide insights that enable a QbD approach to API development, supporting robust design space definition, process optimization, and the maintenance of process performance within that space. 

Malvern Panalytical’s systems help answer questions including:

• How stable is my API during processing?
• Will my API pack together with excipients?
• Will my API flow and how will it react to industrial processes?
• How can I control critical material attributes (CMAs)?
• What is the safety profile of ingredients with respect to elemental impurities?

The poor solubility of many APIs adds to the complexity of ensuring that a molecule has adequate bioavailability. Approaches such as the Developability Classification System (DCS) and Manufacturing Classification System (MCS) help identify molecules likely to meet bioavailability and scale-up requirements. These systems depend on physicochemical data to connect lead optimization and API salt & polymorph selection to the Critical Material Attributes (CMAs) necessary for meeting production needs. 

Common strategies to enhance solubility in API design include reducing particle size, selecting different polymorphs, and using amorphous forms of the molecule. Malvern Panalytical’s systems help answer questions including:

• What solid forms are available?
• Are there multiple polymorphs?
• What is the impact of particle size reduction on particle and polymorph stability?
• How much amorphous content is present, and how can amorphous structures be defined and characterized?

Understanding the stability of solid-form APIs is crucial in lead optimization, salt screening, and process development. Polymorphic transitions can alter dissolution rates, reduce efficacy, and cause adverse reactions, potentially complicating patenting processes. It is therefore vital to select and confirm polymorphic stability, especially when using amorphous forms to enhance solubility, as unexpected crystallization can be detrimental. Knowing and understanding polymorphic behavior ensures API stability and mitigates risks associated with late-emerging polymorphs that could hinder downstream development.

Malvern Panalytical’s solutions help answer questions such as:

• What polymorphic forms of the API are possible?
• How will these polymorphic forms behave as a function of time or upon changes in temperature or humidity?

Eliminating elemental impurities in pharmaceutical products is essential for patient safety. Impurities introduced during processing must be removed throughout development, scale-up, and manufacturing. Access to precise elemental analysis methods is crucial for rapid process development and control.

Introducing X-ray fluorescence and morphological imaging into your workflow can help to accelerate your development processes and shorten your route to market significantly. Fast and non-destructive, these technologies provide robust screening solutions for the elemental purity of your API. 

Malvern Panalytical’s solutions help answer questions such as:

• Has my chemical synthesis process been successful? 
• Did my purification routine work as intended?
• What by-products are affecting my API?

Handover to manufacturing requires the definition of a robust Chemistry, Manufacturing, and Controls (CMC) package. This package must ensure that CMAs are monitored to maintain API product quality and safety. Microstructure and solid-form analysis are often key characterizations, in line with ICH guidance (ICH Q3D, ICH Q6A, and ICH Q1A).

Malvern Panalytical provides comprehensive solutions for instrument qualification and application in a validated (GxP) environment that can help support:

• Quality control of raw materials and intermediates for APIs and excipients, and stability testing for batch release
• Root cause analysis for batch release
• Physicochemical insight to assist process optimization
• In-vitro bioequivalence assessment to aid the transfer of processes or products between sites and/or from old to new processing methods