(T0930-01-01) Capsugel® Enprotect® Capsules Filled with Fecal Microbiota Transplant Placebo Formulation Keep Their Enteric Performance after Six Month Storage at -80°C

Purpose: Fecal Microbiota Transplant (FMT) oral delivery is a challenge. Today, fecal suspensions are concentrated, double-encapsulated in size #0 and #00 capsules and then stored at -80°C for 2 years. Double encapsulation allows FMT to remain in the dosage form and be released in the intestine [1]. However, this adds an extra preparation step, increases cost and limits pediatric indications. Using Capsugel® Enprotect® capsules size #0 would avoid double encapsulation and solve the above mentioned problems. It is a ready-to-fill capsule capable of protecting the payload in the upper gastrointestinal tract. Enteric performance has been demonstrated in vivo in healthy volunteers under both fasting [1] and fed conditions [2]. This study aims to evaluate stability and performance of Enprotect® capsules filled with a placebo FMT formulation during storage at -80°C, and the effect of thawing time.

Methods: The Capsugel® Enprotect® capsules were filled with a FMT placebo formulation consisting of glycerol / 0.9% NaCl solution (80 / 20 %w/w) in which 100mg of uncoated pellets containing 20% of esomeprazole magnesium trihydrate (EMT), a model acid sensitive therapeutic molecule, were dispersed. The capsules were then stored at -80°C for up to 2 years. The performance and stability of the enteric capsules stored in these conditions were tested after 0, 1, 2, 3 and 6 months (study in progress). The performance was evaluated through dissolution test, drug assay and related substances 30 min after thawing as standard protocol of care at the hospital. An extended thawing time of 6 hours was also evaluated on the 2-month time point. Dissolution performance EMT assay and related substances were evaluated using validated methods based on the USP Esomeprazole magnesium delayed-release capsules monograph.

Results: Capsugel® Enprotect® capsules retained their enteric properties after 6-month storage in cold conditions. Figure 1 presents the EMT release profiles of all tested capsules. The capsules conform to the USP dissolution test requirements: less than 10% EMT released after 2 hours in HCl 0.1 N (maximum of 0.9% after 6 month storage) and release of at least 80% of EMT after 30 minutes in pH 6.8 ( >96 % for all timepoints, Table 1). The drug is also chemically stable in the formulation as the content stays in specifications and related substances below 2% (Table 1). The extended thawing time of the capsules before performing the dissolution and assay tests had no impact on the performance of the Enprotect® capsules (Table 1).

Conclusion: Capsugel® Enprotect® capsules are stable and compatible with the FMT placebo formulation stored at -80°C for at least 6 months and thawing time from 30 min to 6 hours.

References: [1] Rump, A., Weiß, F., Schulz, L., Kromrey, M.L., Scheuch, E., Tzvetkov, M., White, T., Durkee, S., Judge, K., Jannin, V., Bellamine, A., Weitschies, W., Grimm, M. 2021 The effect of capsule-in-capsule combinations on in vivo disintegration: A combined imaging and salivary tracer study. Pharmaceutics. 13 2002 https://doi.org/10.3390/pharmaceutics13122002
[2] Rump, A., Kromrey, M.L., Scheuch, E., Jannin, V., Rehenbrock, L., Tzvetkov, M., Weitschies, W., Grimm, M. 2022 In vivo evaluation of a gastro-resistant HPMC-based “Next Generation Enteric” capsule. Pharmaceutics. 14 1999 https://doi.org/10.3390/pharmaceutics14101999
[3] 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


Table 1: Dissolution test, assay and related substances results for EMT pellets in FMT placebo encapsulated in Enprotect® capsules stored at ­80°C for 0, 1, 2, 3 and 6 months.


Figure 1: Esomeprazole release profiles from Enprotect® capsules stored at ­80°C for 0, 1, 2, 3 and 6 months.