As the quest for accelerated development timelines continues, a more innovative approach to the manufacture of clinical products is required.
In this article Dr Stephen Byard, Principal Research Fellow and Dr Mihaela Totolici, Head of Formulation Development, examine how capsule manufacturing can be employed to reduce the time to clinic.
What makes capsules a beneficial choice for Phase I and why are they an ideal option for early clinical trials?
A key advantage of capsule manufacturing for early trials is that you can introduce the drug substance without blending with excipients, circumventing the need for extended stability, formulation development or compatibility studies. This significantly accelerates initiation of clinical trials, providing clear economic benefits, including reduced API consumption, shorter time to market and lower development costs, all without compromising quality. This strategy can often be seamlessly continued for Phase II trials, while more advanced formulation development proceeds in parallel to support later-stage clinical studies or prepare for commercialisation. More broadly, capsules offer several advantages over tablets: they are generally easier to swallow, provide effective taste masking and can enhance bioavailability.
What are the main differences between capsule and tablet manufacturing?
One advantageous difference between capsule and tablet manufacturing is that capsules can be manufactured using an adaptive process, suitable for early phase human trials. Tablet manufacturing on the other hand, tends to require more up-front development and is geared towards Phase III clinical trials and commercial products.
How is flexible capsule manufacturing transforming early clinical trials?
There are different approaches to capsule manufacturing that can be taken during drug development. A conventional approach is to blend drug substance with excipients and subsequently fill capsules with the blended product. Where the drug substance displays suitable flow properties, we are engaging with clinics to supply capsules containing drug substance alone. This allows us to manufacture a relatively high number of capsules in a short period of time, significantly reducing lead time to the clinic. It also circumvents the need for stability studies typically required when the drug substance is blended with excipients. At Arcinova, we offer flexible capsule manufacturing—a tried and tested approach that is increasingly being adopted by our clients.
How will this impact the future of the industry/healthcare?
Flexible capsule manufacturing is particularly transforming clinical trial work prior to commercialisation, including Phase I, Phase II, and human absorption, metabolism and excretion (AME) studies. The drug substance-in-capsule approach significantly accelerates progression into first-in-human studies by removing the need for complex formulation development. This streamlined pathway not only shortens time to market but also ensures patients benefit sooner from potentially life-changing therapies.
Are there any new capsule manufacturing technologies that are having an impact on the industry?
The application of semi-automated equipment for capsule manufacturing is having a significant impact on the industry. One advantage of this instrumentation is its ability to measure the mass of each individual unit produced, providing complete confidence that all clinical material is within specification. Efficiency is further enhanced through the use of semi-automated capsule manufacturing equipment, which eliminates the need to combine capsule content, thereby reducing the requirement for additional analytical testing. Arcinova currently operates two distinct types of instrumentation for capsule manufacturing. We have made significant investments in advanced technology to increase throughput and have implemented enhanced containment measures to ensure operator safety during capsule filling.
What factors should be considered in the decision-making process when choosing capsules over tablets?
To ensure suitability for a flexible capsule manufacturing approach, it is essential to assess how the drug substance disperses in biorelevant media. This involves using state-of-the-art physical and molecular characterisation equipment to gain a comprehensive understanding of drug substance properties and to predict behaviour when applying a powder-in-capsule approach.
At Arcinova, we carefully evaluate the physical and chemical properties of the drug substance, alongside its behaviour in biorelevant media, to confirm that a capsule manufacturing approach is appropriate for its intended clinical application.
If you would like to find out more about capsule manufacturing and the work of our Formulation Development team, please get in touch here