When I first arrived in Colmar to join the Lonza team, I began discovering the world of capsules – the intricacies of their manufacturing and the immense impact they can have on patients and consumers.
Capsules represent one of the oldest pharmaceutical dosage forms, with a history dating back to ancient Egypt. Despite being known and used for centuries, capsules can be transformed into something that reaches far beyond a simple delivery vehicle for its cargo.
I joined Lonza Capsules & Health Ingredients (CHI) in 2022 – around the time when Lonza launched an excellent example of a capsule going far beyond a simple delivery solution. The award-winning Capsugel® Enprotect® capsule is the first capsule with built-in enteric properties, manufactured via an innovative proprietary double-layered manufacturing technology. This capsule has been extensively characterized through multiple collaborations. Outcomes of these studies have shown its ability to protect sensitive compounds - small molecules and proteins[1] - from the harsh and acidic gastric environment.
In vivo evaluations have confirmed that the capsule enabled the delivery of its content in the distal intestine of healthy volunteers, with consistency between fasted and post-prandial (fed) conditions[2,3]. These results demonstrated that the Capsugel® Enprotect® capsule offers a ready-to-use solution for oral administration of fragile compounds, such as acid-sensitive molecules, peptides, proteins, mAbs and mRNA.
Tailoring capabilities for targeted capsules
The features of Capsugel® Enprotect® capsules, alongside other capsules from our portfolio, may not always be suited to meet the needs of our customers, who need to solve drug delivery challenges through innovative delivery solutions.
To answer this pressing market need, we recently launched Innovaform™ Accelerator, a 700m2 innovation hub located in Colmar, France. We are a multi-disciplinary team of scientists with diverse expertise, from formulation development to encapsulation processes, including polymer and analytical sciences.
Our aim is to cultivate collaborations and co-innovate with our pharma customers to create cutting-edge solutions that fit their exact needs. Whether tackling poor solubility, protecting sensitive compounds from acidic or enzymatic degradation, or ensuring targeted release in the gut, we are determined to find new ways to solve drug delivery challenges.
Our lab-scale capsule manufacturing equipment enables fine-tuning of capsule sizes, designs, and polymer formulations and brings the capability to manufacture single or bi-layered products. These capabilities expand the possibilities for the integration of functionalities, which allows our customers to evaluate customized capsules. These can be used for proof-of-concept validation by engaging reasonable resources for the development and manufacturing of small batches, while taking advantage of in-depth capsule know-how. Furthermore, as we develop customized capsule solutions, we always bear in mind the scalability of the designed product.
As our Colmar site also houses large-scale commercial capsule manufacturing, our team interacts with process engineers to validate all aspects related to the industrialization of the products. Colmar also serves as Lonza CHI’s largest R&D center, allowing for a rich, collaborative environment where capsule and nutraceutical formulation experts work side by side to deliver comprehensive solutions to our customers.
Solutions beyond capsules
Capsules alone cannot address all drug delivery issues without an appropriate formulation. Therefore, our team relies on strong experience with pharmaceutical formulation development and enabling formulations to improve the oral bioavailability of small and large molecules, such as lipid-based formulations. My personal connection to this area dates back to my PhD studies; my PhD thesis was focused on the development of solid lipid nanoparticles to increase the oral bioavailability of encapsulated leuprolide, a model hydrophilic peptide used in the treatment of prostate cancer[4-6].
Our laboratory space is equipped with advanced tools to formulate, characterize, and analyze powders, solutions, and suspensions to support these formulation development activities.
We offer expertise and equipment to fill capsules with a variety of materials, including powders, pellets, minitabs, suspensions, solutions, and semi-solid formulations. These capacities allow us to validate and optimize filling processes and/or the formulation to guarantee smooth encapsulation operations at customer facilities. These capacities are also used to provide non-GMP filled materials for pre-clinical evaluations of developed prototypes to de-risk early-stage development with practical testing.
A comprehensive approach to drive innovation
One of the key advantages and greatest strengths of our Innovaform™ offering is the diversity of expertise within our team, spanning formulation development, analytics, and polymer science. Indeed, we can combine capsule knowledge with the ability to step in our customer’s shoes, enabling a collaborative and comprehensive approach to their challenges. We are not simply providing capsules; we are developing customized, targeted solutions that respond to the nuanced needs of each customer and the respective product.
As a member of the Innovaform™ Accelerator, I’m continually impressed by our team's creativity, ingenuity, and dedication to every project. When I joined Lonza CHI, I had not anticipated the science and innovation hiding behind such a seemingly “simple” product as a capsule.
Capsules are often seen as mere commodities, but the products we are developing at Lonza Colmar have proven to me how impactful they can be in improving advanced drug delivery systems and making a real difference in therapeutic outcomes and patients’ lives.
References:
[1] V. Jannin, C. Duysburgh, V. Gonzalez, M. Govaert, M. Agisson, M. Marzorati, N. Madit, 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 (2023) 122441. https://doi.org/10.1016/j.ijpharm.2022.122441.
[2] A. Rump, M.-L. Kromrey, E. Scheuch, V. Jannin, L. Rehenbrock, M.V. Tzvetkov, W. Weitschies, M. Grimm, In Vivo Evaluation of a Gastro-Resistant HPMC-Based “Next Generation Enteric” Capsule, Pharmaceutics 14 (2022) 1999. https://doi.org/10.3390/pharmaceutics14101999.
[3] M. Grimm, A. Rump, M.-L. Kromrey, F. Morof, C. Dumont, V. Jannin, M.V. Tzvetkov, W. Weitschies, In Vivo Evaluation of a Gastro-Resistant Enprotect® Capsule under Postprandial Conditions, Pharmaceutics 15 (2023) 2576. https://doi.org/10.3390/pharmaceutics15112576.
[4] C. Dumont, S. Bourgeois, H. Fessi, P.-Y. Dugas, V. Jannin, In-vitro evaluation of solid lipid nanoparticles: Ability to encapsulate, release and ensure effective protection of peptides in the gastrointestinal tract, International Journal of Pharmaceutics 565 (2019) 409–418. https://doi.org/10.1016/j.ijpharm.2019.05.037.
[5] C. Dumont, V. Jannin, C. Miolane, Q. Lelong, J.-P. Valour, S. Urbaniak, H. Fessi, S. Bourgeois, A proof-of-concept for developing oral lipidized peptide Nanostructured Lipid Carrier formulations, Journal of Drug Delivery Science and Technology 54 (2019) 101394. https://doi.org/10.1016/j.jddst.2019.101394.
[6] C. Dumont, A. Beloqui, C. Miolane, S. Bourgeois, V. Préat, H. Fessi, V. Jannin, Solid lipid nanocarriers diffuse effectively through mucus and enter intestinal cells – but where is my peptide?, International Journal of Pharmaceutics 586 (2020) 119581. https://doi.org/10.1016/j.ijpharm.2020.119581.