Traditionally, capsules have been used to deliver medicines to the stomach by oral administration. However, standard capsules have limitations when it comes to delivering medication further down the gastrointestinal (GI) tract.
This is because of their fast dissolution in the stomach and the release of the active pharmaceutical ingredient (API) in the acidity and enzymes of the stomach.1
To overcome these limitations, complex multistep processes have been developed to create delayed-release solid oral dosage forms that can pass through the stomach and protect the API until it reaches its intended destination.
Besides the challenges of delivering medicine to the small intestine, the manufacturing process also includes bottlenecks that impact the entire industry.
For example, established capsule production and formulation methods involve challenges such as formulating APIs that require protection from harsh processing conditions during development or production.
Although these obstacles might seem to be minor “product issues,” they represent a pressing problem for the capsule manufacturing industry. This situation has led to a radical shift and the creation of capsules with embedded delayed-release properties to overcome these hurdles.2,3
With these new types of capsules, no additional post-filling processes — such as coating with enteric polymers using solvents and/or heat — are needed. As a result, manufacturers and pharmaceutical companies can use these capsules more easily without post-manufacturing treatments.
At Lonza, we believe that capsules with embedded functionality are an ever-growing trend and, during the coming years, will become a transformative force for manufacturers, pharmaceutical companies and patients alike.
Traditionally, capsules are understood to be containers for the fill material. However, utilising novel technologies and materials, we can now develop capsules with specific characteristics that bring novel attributes to specific applications.
These improvements work alongside advancements in new APIs such as peptides and proteins.4 New capsules protect APIs and ensure effective payload delivery by optimising APIs delivery conditions — effectively leading from an “API-first” perspective.
The ultimate goal of these novel capsule technologies is to release the entire API, all at once, to ensure the delivery of a high drug concentration in a specific location and favour API absorption.
These shifts are also vital in terms of enabling precision targeting with capsules; and, when it comes to negating any risks and issues such as efficacy and drug release variability, target site accessibility and regulatory compliance, only scientifically proven approaches are viable.
With an increasing number of failures observed during different phases of clinical development, there are significant potential monetary losses within clinical trials. Companies must invest in technology based and proven approaches to negate these losses as a long-term sustainable solution.
How technology is helping to adapt and deliver new payloads
The technologies and processes in capsules are continuously changing and advancing, notably regarding the type of payloads being encapsulated (from traditional solid or liquid forms to devices).
These advancements bring promising and unique opportunities, including new drugs being delivered using enhanced capsules and formulated in liquid, powder and multiparticulate forms.
Considering live biotherapeutic products (LBPs), this entirely new drug type is a growing trend in the market. Oral LBPs became available on the market very recently, with the first LBP only being available in capsule form.
The new products in development are designed to target the distal small intestine or the colon to deliver the payload to the target site of action. Delayed-release capsules are being tested to simplify the manufacturing process of these fragile drugs.
Proteins and peptides were typically delivered intravenously. There are now opportunities to develop oral formulations, with two products currently available for such delivery: a tablet form or a delayed-release capsule.
Beyond these, developers are working on reformulating peptides into protective, enhanced capsules. This shift to oral formulation will improve patient adherence and quality of life.
Ultimately, capsule solutions must be able to protect, target and deliver their fill. In the stomach, the use of fast-dissolution capsules can ensure drug assimilation before gastric emptying.
Additionally, by protecting payloads from gastric impairment using new capsule solutions, we can now ensure the precise targeting of specific digestive tract segments.
The landscape of new technologies in capsules and delivery is very promising, but there is a need for the industry to plan effectively for the future.
The importance of partnering
Given the unique needs of APIs and capsules, working with an experienced contract development and manufacturing organisation (CDMO) with the right experience, expertise and equipment is key for successful and timely capsule development and formulation.
In the case of CDMOs, specialist facilities that can be dedicated to capsule development are becoming a key topic. Available facilities represent a growing trend throughout the industry and are expected to become even more critical as the capsule landscape shifts towards enhanced capabilities.
To meet the growing need for specialist capsule development and manufacturing solutions and to develop new precision targeting methods and payload delivery options, Lonza has established Capsule Application Lab Services (CALS) at its site in Colmar, France.
With a focus on ensuring precision targeting and developing technology to adapt and deliver new payloads, CALS is continually tilted towards the ever-changing needs of our partners and the advancing health landscape.
Precision targeting and payload delivery are processes and methods with great potential for capsule development. The advances in this space mark an exciting new chapter for capsule delivery.
Now, it’s paramount for the industry to harness this potential and deliver the wide-ranging benefits of such promising innovations.
References
- Z. Vinarov, et al., “Current Challenges and Future Perspectives in Oral Absorption Research: An Opinion of the UNGAP Network,” Advanced Drug Delivery Reviews 171, 289–331 (2021).
- A. Rump, et al., “In Vivo Evaluation of a Gastro-Resistant HPMC-Based “Next Generation Enteric” Capsule,” Pharmaceutics 14, 1999 (2022).
- M. Grimm, et al., “In Vivo Evaluation of a Gastro-Resistant Enprotect Capsule Under Postprandial Conditions,” Pharmaceutics 15, 2576 (2023).
- V. Jannin, et al., “In Vitro Evaluation of the Gastrointestinal Delivery of Acid-Sensitive Pancrelipase in a Next Generation Enteric Capsule Using an Exocrine Pancreatic Insufficiency Disease Model,” International Journal of Pharmaceutics 630, 122441 (2022).
