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The increasing number of breakthroughs in small molecule drug development are exciting, but corresponding workflows are complex and require much more tailored approaches to ensure successful upstream and downstream processing, drug approvals and commercialization.

Accelerating Small Molecule Advancements: The Power of Collaboration Between CDMOs and Biotechs

International Journal of Pharmceutics: In Vitro: The dissolution characteristics of five capsules (Next Generation Enteric [NGE], Vcaps® Enteric [VCE], VCE DUOCAP® [VCE/VCE] system, Hard Gelatin Capsule [HGC] as negative control, and Creon® 10,000 U as market reference) were evaluated using an in vitro simulation of the stomach and upper intestinal tract with an acidic duodenal incubation (pH 4.5 for the first 10 min, pH 6 for the remaining 17 min) to simulate exocrine pancreatic insufficiency. Caffeine was a marker of capsule dissolution, and tributyrin to butyrate conversion measured pancrelipase activity. All capsules were filled with pancrelipase; the NGE, VCE, VCE/VCE, and HGC capsules also contained 50 mg caffeine. Caffeine was released first from the HGC capsule, followed by the VCE, NGE, and VCE/ VCE capsules. Pancrelipase activity followed this trend and demonstrated a similar activity level over time for the NGE, VCE/VCE, and Creon® capsules. The HGC formulation confirmed gastric degradation of unprotected pancrelipase. NGE capsules provided similar protection to the simple fill formulation as observed for the complex formulation of the Creon® capsule in a setting with increased pepsin activity and may hasten the time needed to go from formula development to first-in-human studies for pH sensitive drugs or those requiring small intestine targeting. 

In vitro evaluation of the gastrointestinal delivery of acid-sensitive pancrelipase in a next generation enteric capsule using an exocrine 	pancreatic insufficiency disease model

Introducing Lonza Capsules & Health Ingredients' groundbreaking enteric manufacturing technology - the Capsugel® Enprotect® capsule. This unique bi-layer capsule with the Coni-Snap® secure closure design utilizes HPMC and HPMC-AS polymers. It protects acid-sensitive APIs and enables rapid dissolution release at pH 6.8 without the need for additional excipients. The bi-layer manufacturing technology streamlines drug development processes, while personalized oral dose customization enhances product differentiation. Partner with us to revolutionize the microbiome market, overcome enteric delivery challenges, and drive innovation in modern healthcare.

Capsugel® Enprotect® capsule (Aug 2023)

Invivo: Many orally dosed APIs are bioavailable only when formulated as an enteric dosage form to protect them from the harsh environment of the stomach. However, an enteric formulation is often accompanied with a higher development effort in the first place and the potential degradation of fragile APIs during the coating process. Ready-to-use enteric hard capsules would be an easily available alternative to test and develop APIs in enteric formulations, while decreasing the time and cost of process development. In this regard, Lonza Capsugel® Next Generation Enteric capsules offer a promising approach as functional capsules. The in vivo performance of these capsules was observed with two independent techniques (MRI and caffeine in saliva) in eight human volunteers. No disintegration or content release in the stomach was observed, even after highly variable individual gastric residence times (range 7.5 to 82.5 min), indicating the reliable enteric properties of these capsules. Seven capsules disintegrated in the distal part of the small intestine; one capsule showed an uncommonly fast intestinal transit (15 min) and disintegrated in the colon. The results for this latter capsule by MRI and caffeine appearance differed dramatically, whereas for all other capsules disintegrating in the small intestine, the results were very comparable, which highlights the necessity for reliable and complementary measurement methods. No correlation could be found between the gastric residence time and disintegration after gastric emptying, which confirms the robust enteric formulation of those capsules

In Vivo Evaluation of a Gastro-Resistant HPMC-Based "Next Generation Enteric" Capsule

The Lonza Capsule Application Lab is uniquely focused on solving technical issues and creating new solutions related to dosage form and delivery. We work together to leverage our scientific and technical knowledge helping to improve your manufacturing process and methodology to deliver customized solutions. 

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Oral administration is the preferred route of delivery for therapeutic molecules due to its convenience. However, most New Chemical Entities (NCE) exhibit physico-chemical properties limiting their absorption in the gastrointestinal (GI) tract, with almost 70% of identified molecules facing solubility issues in aqueous GI fluids according to Pharmacircle data from March 2022. Lipid-based formulations (LBF) is an interesting approach to enhance oral bioavailability of poorly water-soluble (PWS) drugs, including small molecules and macromolecules such as peptides and proteins. 