(T1330-01-05) Evaluation of the Compatibility of Capsugel® Enprotect® Capsules with Solid Phase Excipients to Accelerate Developments of New Enteric Drug Products

Purpose: Enteric dosage forms are necessary to orally dose a wide range of therapeutic molecules sensitive to the acidity and/or enzymes of the gastric environment. To facilitate the development of these dosage forms, Capsugel® Enprotect® capsule was launched in 2022 after confirming its ability to protect encapsulated proteins from acid and enzymes degradation [1] and to open in the distal small intestine independently of gastric residence time [2]. This study aims to evaluate the compatibility of this new capsule with solid-phase excipients commonly used in powder-filled capsule in order to accelerate developments of new enteric drug products.

Methods: The compatibility of 8 solid-phase excipients (e.g. lactose, microcrystalline cellulose, mannitol, saccharose, sorbitol…) was evaluated through disintegration test, dissolution test, and friability test. Disintegration properties of the capsules was evaluated using the EP method for gastro-resistant capsules. Dissolution performance was evaluated after emptying the capsules from the tested excipient and filling them with uncoated pellets of esomeprazole magnesium trihydrate (EMT), an acid sensitive therapeutic molecule, using the USP Esomeprazole magnesium delayed-release capsules method. For both disintegration and dissolution tests, Capsugel® Enprotect® capsules filled with tested excipients were stored up to 6 months at 40°C/75%RH. Friability test, or mechanical evaluation, was performed by exposing filled capsules to the impact of a 100 g weight dropped from a height of 8 cm above the capsules. Before conducting this test, capsules were equilibrated for one month at various relative humidity.

Results: Capsugel® Enprotect® capsules retained their enteric properties after 6-month storage in accelerated conditions with all tested excipients. Indeed, all capsules complied to EP disintegration test with no opening of the capsules after 2 hours in HCl 0.1 N and opening in pH 6.8 phosphate buffer in less than 30 minutes, as detailed in Table 1. The capsules also fulfilled USP dissolution test for EMT requirements with no release after 2 hours in HCl 0.1 N (degradation product < 0.6%) and release of at least 96% of EMT after 30 minutes in pH 6.8. Finally, the mechanical properties of the filled capsules were similar to those of empty capsules equilibrated at the same relative humidity, confirming the good compatibility of the tested excipients with Capsugel® Enprotect® capsules.

Conclusion: Capsugel® Enprotect® capsules are compatible with all tested excipients and can be used for the development of powder-based enteric dosage forms.

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.

Enteric performance of filled Capsugel® Enprotect® capsules after 6–month storage at 40°C and 75% RH