Diroximel fumarate delayed-release capsule for multiple sclerosis treatment
A novel 462 mg delayed-release diroximel fumarate capsule formulation for relapsing-remitting multiple sclerosis that reduces pill burden from two capsules to one while maintaining therapeutic drug levels and minimizing gastrointestinal disturbances associated with methanol production during esterase hydrolysis.
Overview
This research presents an innovative single 462 mg delayed-release capsule formulation of diroximel fumarate for patients with relapsing-remitting multiple sclerosis (RRMS). The current marketed product, Vumerity®, requires patients to take two 231 mg capsules per dose. This new formulation consolidates the dosage into a single capsule, aiming to improve patient adherence while maintaining comparable drug release characteristics.
Fumaric acid esters are metabolized to monomethyl fumarate, which activates the Nrf2 pathway—a cellular defense mechanism with anti-inflammatory and neuroprotective effects relevant to MS treatment. A key challenge with existing formulations is that esterase hydrolysis produces methanol, contributing to gastrointestinal disturbances. The proposed formulation addresses this issue by optimizing drug release while reducing pill burden for patients.
Technical specifications
Formulation strategies explored:
- Powder blends in capsules with enteric coating
- Tablets in capsules with enteric coating
- Tablets in enteric capsules with additional coating
- Enteric-coated mini-tablets in capsules
Key technical findings:
- All formulations demonstrated acid resistance meeting pharmacopeial specifications, with less than 10% drug release in the acid stage (0.1 N HCl)
- In the buffer stage (sodium phosphate buffer pH 6.5), drug release patterns remained comparable to the marketed two-capsule regimen
- Collaborative formulation and dissolution testing conducted with IQGEN-X Contract Research Organization and Bombay College of Pharmacy
Mechanism of action:
The active metabolite monomethyl fumarate activates the Nrf2 pathway, providing anti-inflammatory and neuroprotective benefits for RRMS patients.
Technology readiness level
This technology is currently at an early-to-mid stage of pharmaceutical development. In vitro dissolution studies have been completed, confirming that the single 462 mg capsule achieves drug release patterns comparable to the marketed two-capsule regimen. Acid resistance and buffer-stage dissolution testing have met specifications.
Future validation plans include:
- Investigating critical formulation and process factors including API particle size variations, enteric coating weight gain, and curing time optimization
- Assessing impact on product description, assay, related substances, dissolution, and water content parameters
- Conducting stability studies in both HDPE bottles and Alu-Alu blister packs
- Performing in vivo pharmacokinetic studies on human subjects to corroborate in vitro findings
The formulation is not yet commercially available and requires further optimization and clinical validation before regulatory submission.
About Bombay College of Pharmacy
Bombay College of Pharmacy is a specialized, government-aided autonomous institution in Mumbai, offering undergraduate, postgraduate, and doctoral education with a strong research and professional orientation. Its modern laboratories and industrial pharmacy facilities support analytical work, formulation development, and pilot-scale activity, with equipment funded by government, industry, and management sources. The college connects with pharmaceutical companies through sponsored research, consultancy, formulation and preformulation work, internships, and technical training; its Innovation Council promotes entrepreneurship and startups. Research funding has included India’s Department of Science and Technology, Department of Biotechnology, AICTE, and University Grants Commission. Institutional innovation structures support translation toward industry.
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