Clostridioides difficile infection (CDI) remains a significant public health concern, particularly in healthcare settings. Characterized by severe diarrhea and colitis, CDI often arises following antibiotic treatment that disrupts the natural gut microbiota. While standard antibiotic therapies can be effective, recurrence rates remain high, with up to 25% of patients experiencing relapse after initial treatment. In response to this challenge, Fecal Microbiota Transplantation (FMT) has emerged as a highly effective therapeutic strategy, particularly for recurrent CDI. Numerous randomized controlled trials and meta-analyses have demonstrated FMT’s superiority over antibiotics, with clinical success rates exceeding 90% in many studies [1–4].

FMT involves the transfer of processed stool from a healthy donor into the gastrointestinal tract of a patient, with the goal of restoring a balanced and diverse microbial community. Traditionally administered via colonoscopy or nasoduodenal tube, FMT has evolved with the development of encapsulated formulations, offering a less invasive, more patient-friendly alternative. Encapsulated FMT has shown comparable efficacy to traditional methods [5], while improving accessibility, reducing procedural risks, and lowering healthcare costs. However, despite its growing adoption, encapsulated FMT still lacks standardized processing and validation protocols, as highlighted in a recent scoping review of 44 studies [6]. This heterogeneity underscores the need for robust, reproducible methods to ensure product quality, safety, and clinical efficacy.

Capsule-Based FMT: Progress and Challenges

Encapsulated FMT formulations typically involve freezing or lyophilizing donor stool, followed by encapsulation in acid-resistant capsules. These capsules must protect the microbiota from gastric acid and release their contents in the intestine. To address this, current FMT capsules often rely on double encapsulation techniques, where fecal material is enclosed within two capsule shells to provide sufficient acid resistance. While effective, this method introduces additional manufacturing complexity, increases costs, and limits the use of smaller capsule sizes, particularly important for pediatric applications.

Scientific studies have demonstrated the feasibility of using enteric capsules for FMT delivery [5–7]. These capsules are designed to resist disintegration in the stomach and release their contents in the intestine, where the microbiota can colonize effectively. Despite these advances, the need for a more efficient, scalable, and robust solution remains.

Capsugel® Enprotect® Capsules for FMT: Supporting Evidence

Lonza’s Capsugel® Enprotect® capsules represent a next-generation solution for oral FMT delivery. These bi-layered capsules, composed of hydroxypropyl methylcellulose (HPMC) and HPMC acetate succinate (HPMC-AS), provide intrinsic enteric protection without the need for post-filling coating or double encapsulation. Their performance has been validated in vivo under both fasted and fed conditions, confirming reliable disintegration in the distal intestine [8–10]. Recent studies have extended this validation to FMT applications [6,11]. Capsugel® Enprotect® capsules filled with a placebo FMT formulation, comprising glycerol and saline with dispersed esomeprazole magnesium trihydrate (EMT) as a model acid-sensitive compound, were stored at -80°C for up to 12 months. Across all time points, the capsules retained their enteric properties, with less than 1% EMT release in acidic conditions and over 96% release in pH 6.8 buffer within 30 minutes. Chemical stability was also maintained, with EMT content within specification and related substances below 2% [11]. Furthermore, extended thawing times of up to 6 hours had no impact on capsule performance, supporting their use in clinical environments where flexibility in handling is essential.

These findings confirm that Capsugel® Enprotect® capsules offer a robust, scalable, and patient-friendly alternative to traditional double-encapsulation methods for FMT delivery.

Learn more about Capsugel® Enprotect® Capsules 

$ -80°C pH 6.8

References

  1. van Nood E, et al. N Engl J Med. 2013;368:407–415.
  2. Baunwall SMD, et al. EClinicalMedicine. 2020;29–30:100642.
  3. Kao D, et al. JAMA. 2017;318:1985–1993.
  4. Hvas CL, et al. Gastroenterology. 2019;156:1324–1332.e3.
  5. Cold F, et al. Ther Adv Gastroenterol. 2021;14:17562848211041004.
  6. Rågård N, et al. Ther Adv Gastroenterol. 2025;18:1–25. doi:10.1177/17562848251314820.
  7. Youngster I, et al. JAMA. 2014;312(17):1772–1778.
  8. Rump A, et al. Pharmaceutics. 2022;14(10):1999.
  9. Grimm M, et al. Pharmaceutics. 2023;15(11):2576.
  10. Jannin V, et al. Int J Pharm. 2023;630:122441.
  11. Jannin V, et al. Lonza, 2025.
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