Drug Substance

Arcinova’s material science team has extensive expertise in solid form screening and selection and works closely with the Drug Substance team in order to identify the most appropriate drug substance form for development. Services include: 

Salt Selection: Poor bioavailability or instability of a drug substance can often be solved/improved by screening different salt forms.  The selection of the most appropriate salt can not only improve the physicochemical properties but identifying all developable salts can strengthen the intellectual property of the drug substance. The choice of counterions is typically based on the pKa of the drug substance, the relevance for the expected dosage form, and the know-how of our experts.   

Polymorph Screening: To meet regulatory requirements, the polymorphic behaviour of a drug substance needs to be assessed and the polymorph chosen for development needs to be fully identified/characterised. Identifying the polymorph landscape can also strengthen intellectual property. 

Amorphous Dispersions: Amorphous forms can have increased solubility and bioavailability in comparison with their crystalline form. However crystalline materials tend to be more stable and amorphous material can recrystallize over time but can be stabilised as an amorphous solid dispersion. Our team of experts can also support this type of study

Crystallisation Development: Supporting the drug substance development team, purification steps can be improved and yield increased by integrating a solid state approach to recrystallization processes

Solid State Characterisation: A wide range of analytical techniques are available to fully characterise solid state forms including:

• X-Ray powder diffraction (XRPD)
• Thermal Analysis (DSC, TGA)
• Hygroscopy (DVS)
• Hot stage microscopy
• Particle size distribution and particle enumeration 
• Surface Area
• Solution and Solid State NMR
• FT-IR
• Dissolution/disintegration 

Arcinova has access to scale up and pilot plant assets, complementing the existing facilities at the Alnwick site. The pilot plant has a capacity range between 50 L and 1300 L, and is capable of producing 5-100 kg in batch. We have a range of internal manufacturing assets (batch, CSTR, trickle bed and plug flow) from multigram to multikilogram capacity (multitonne p.a capability). 

The combined offering allows Arcinova to meet our clients’ drug substance requirements from preclinical through to full scale commercial phases. The scale up process is executed by a highly experienced Arcinova manufacturing team, providing our clients with a secure source of supply for technically challenging projects.

Arcinova has access to additional scale up and pilot plant assets to complement our on-site facilities. Our investment in innovative and flexible modular manufacturing technology will further enhance our capabilities. The technology enables us to quickly configure reactors for drug substance (API) manufacture and then rapidly reassemble reactors for the next project.

Our facilities can provide both GMP and non-GMP manufacturing with the ability to generate kg per day quantities.

Current capabilities include: 

• 5 L GMP and non GMP process chemistry facilities with full thermal control 
• 20 L GMP state of the art reactor streams housed in dedicated walk in fume cupboards with operating temperatures from -90°C up to +180°C.
• Full integration of reactor stream data logging to a dedicated server, enabling GMP monitoring of all key reaction parameters (pressure, temperature etc.) and real time process optimisation.
• State of the art dedicated material storage area enabling safe storage of a range of chemical classes and segregation of quarantine and released materials.
• Flexible continuous manufacturing units (Flowsyn, Trickle Bed and Salamander reactors with pressure capabilities up to 50 Bar and operating temperatures up to 180 °C). These equipment trains have the capacity to generate kilogram quantities of materials per day.
• Automated parallel reactor streams with ReactIR and integrated calorimetry (HFCAL) and offgassing measurement capability
• Onsite 100L reactors, fully operational in 2021
• A range of isolation and drying options, including mobile filter dryers (316 Stainless Steeln and Hastelloy MOC) with up to 15 kilogram capacities. 
• Containment systems for handling compounds up to and including Safebridge Band 3. 

Highly trained and experienced ARCINOVA chemists can support all aspects of drug substance development, typically selecting and developing optimum synthetic routes for drug substance manufacture. We combine rapid route selection with the implementation of innovative technological solutions to produce the shortest, most efficient scalable pathway to a drug substance.  Our focus is on process velocity and economy, product purity, process scalability and safety. The drug substance can then be scaled to multi-kg quantities to support direct client supply, or as part of an integrated in-house drug substance / drug product package to support clinical trial or full scale commercialisation programmes.

The Arcinova Process Research and Development philosophy targets optimal velocity for drug substance delivery. This ensures drug substance supply to meet our clients urgent clinical trial needs, while enhancing process efficiency and robustness to lower costs and generate higher purity. Our work also involves defining the best route for product manufacturing scalability.