Effective drug delivery remains a core challenge in modern medicine, as many active pharmaceutical ingredients (APIs) degrade or lose efficacy before reaching their target site. Factors like gastrointestinal pH, enzymatic breakdown, and poor solubility impact absorption, reducing therapeutic effectiveness. Innovative delivery systems are essential to improve stability, ensure targeted release, and enhance patient outcomes across various treatments.
Purpose: Lonza’s Capsugel® Enprotect® capsules are designed for therapeutic delivery, ensuring that active compounds reach the small intestine intact.
Mechanism: Capsugel® Enprotect® capsules offers robust acid resistance, enabling sensitive compounds to bypass the stomach’s acidic environment and deliver active ingredients directly to the small intestine
Applications: The unique property of Capsugel® Enprotect® capsule has numerous advantages for applications in the pharmaceutical industry, particularly for formulations that require targeted intestinal release without the complexities and costs associated with traditional coating processes.
Key Features of Capsugel® Enprotect® Capsules
The Capsugel® Enprotect® capsules are made from hydroxypropyl methylcellulose (HPMC) combined with HPMC acetate succinate (HPMC-AS), creating a material structure that provides gastro-resistance up to pH 6.0 without additional coating1. This innovative design ensures that the capsules remain intact in acidic environments, avoiding premature release of their contents in the stomach. Instead, they release their payloads in the intestine. Such precision in drug delivery reduces degradation risks for acid-sensitive APIs and enhances bioavailability.
Laboratory tests indicate that Capsugel® Enprotect® capsules maintain integrity during exposure to simulated stomach conditions, demonstrating no significant degradation or premature drug release in acidic media over two hours1. In clinical trials in healthy volunteers, they disintegrate predictably in the distal small intestine, delivering contents directly to the jejunum or ileum—a process observed through techniques like MRI and salivary caffeine detection in human trials1.
A second trial published in 20232 confirm no significant degradation or premature drug release in acidic media for over two hours. This integrity was maintained consistently across both fasted and fed conditions. The data from MRI tracking and salivary caffeine appearance confirmed that:
- The capsules resisted gastric environments, even with extended post-meal residence (up to 240 minutes).
- No leakage or early disintegration occurred in the stomach, regardless of food intake.
- Confirm the disintegration is predominantly occurred in the jejunum or ileum, ensuring targeted release in the small intestine
These data underscore the capsules’ reliable enteric performance, making them suitable for protecting sensitive compounds from acidic environments and enabling precise drug delivery.
Internal compendial disintegration tests
| TestCondition | pH value | 1.2 | 4.5 | 4.5 | 4.5 | 5.0 | 5.4 | 6.0 | 6.4 | 6.8 |
| Media | HCl 0.1 M | Phosphate medium | Citrate buffer | Citrate buffer saline | Citrate Buffer | Citrate Buffer | Citrate Buffer | Phosphate buffer | Phosphate buffer | |
| Disintegrationresults | # Capsules open | 0/6 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 | 3/3 | 3/3 | 6/6 |
| Time (min) | NA | NA | NA | NA | NA | NA | >120 | <15 | <15 |
Table 1: Enteric capsules withstand disintegration in various acidic media up to pH 6.0
Benefits for Live Biotherapeutics Delivery and Pharmaceutical Applications
Capsugel® Enprotect® capsules address specific challenges in both live biotherapeutics and pharmaceutical sectors. For live biotherapeutics, delivering live microorganisms to the intestine without stomach degradation is crucial for efficacy. Capsugel® Enprotect® capsule technology’s pH-resistant material ensures that beneficial bacteria are released directly into the small intestine, potentially enhancing live biotherapeutics viability and supporting gut health more effectively than traditional capsules.
In pharmaceuticals, Capsugel® Enprotect® capsules provide distinct advantages for acid-sensitive compounds. Lonza’s research highlights the capsule’s compatibility with small molecules, peptides, proteins, and even nucleic acid-based drugs, which are often compromised in the acidic gastric environment. For example, sensitive enzymes like pancrelipase have shown high activity rates when encapsulated with Capsugel® Enprotect® capsules, comparable to industry-standard products, while achieving greater stability in stomach simulations3. This functionality is particularly valuable for treatments targeting chronic gastrointestinal conditions, such as inflammatory bowel diseases, where site-specific delivery can reduce side effects and improve therapeutic efficacy3.
Streamlined Development and Manufacturing
The Capsugel® Enprotect® capsule’s design simplifies the drug development process. By eliminating the need for acid-resistant coatings, these capsules can accelerate pre-clinical and clinical timelines for new drugs. Lonza recently introduced a smaller Capsugel® Enprotect® capsule size (Size 9), designed for rodent studies, which aids researchers in preclinical drug testing. This approach allows API testing in final dosage forms from the early stages, supporting quicker transitions to human trials and ensuring formulation consistency across development phases3.
Moreover, Lonza’s newly inaugurated Innovaform™ Accelerator facility in Colmar, France, acts as a hub for formulation innovation, focusing on optimizing capsule-based drug delivery. The center offers custom development for Capsugel® Enprotect® capsules, allowing pharmaceutical companies to evaluate and tailor capsule performance to meet specific drug requirements. This facility embodies Lonza’s commitment to co-innovation, bringing together expertise to overcome complex delivery challenges in a collaborative setting4.
Future Prospects and Industry Impact
Lonza’s Capsugel® Enprotect® capsule technology is offering a big opportunity to improve enteric drug delivery. By improving the stability and targeting of sensitive APIs, these capsules facilitate the development of novel therapies, especially for gastrointestinal and metabolic disorders. The expansion of this technology through dedicated facilities like the Innovaform™ Accelerator underscores Lonza’s vision for supporting pharmaceutical innovation. As demand for targeted drug delivery grows, Capsugel® Enprotect® capsules position Lonza as a key enabler of advanced therapeutic solutions, paving the way for the next generation of health ingredients and drug delivery systems.
This technological advancement has the potential to improve patient compliance and outcomes increasing efficacy and bioavailability APIs.
This content was developed in collaboration with Lonza
Reference
- Rump, A.; Kromrey, M.-L.; Scheuch, E.; Jannin, V.; Rehenbrock, L.; Tzvetkov, M.V.; Weitschies, W.; Grimm, M. In Vivo Evaluation of a Gastro-Resistant HPMC-Based “Next Generation Enteric” Capsule. Pharmaceutics 2022, 14, 1999. https://doi.org/10.3390/pharmaceutics14101999
- Grimm, M., Rump, A., Kromrey, M.L., Morof, F., Dumont, C., Jannin, V., Tzvetkov, M.V., Weitschies, W. 2023 In vivo evaluation of a gastro-resistant Enprotect® capsule under postprandial conditions. Pharmaceutics. 15 2576. https://doi.org/10.3390/pharmaceutics15112576
- Jannin V, Duysburgh C, Gonzalez V, Govaert M, Agisson M, Marzorati M, Madit N. In vitro evaluation of the gastrointestinal delivery of acid-sensitive pancrelipase in a next generation enteric capsule using an exocrine pancreatic insufficiency disease model. Int J Pharm. 2023 Jan 5;630:122441. https://doi.org/10.1016/j.ijpharm.2022.122441
- Lonza release: https://www.lonza.com/
