How Lipid-Based Softgels Protect Oral Peptides from Degradation

Karunakar Sukuru, RPh, PhD, segment vice president of global product development and innovation at Catalent Pharma Solutions, spoke to BioPharm International® ahead of the American Association of Pharmaceutical Scientists’s (AAPS) 2026 PharmSci 360 conference. In this first segment, he discusses barriers to oral peptide delivery and how lipid-based softgels address them. Dr Sukuru is scheduled to present “Patient-Centric Oral Peptide Delivery Using Softgel and Lyophilized ODT Technologies” during the symposium “Emerging Strategies for Oral Macromolecular Delivery” on Oct. 28, 2026.

Dr Sukuru says oral peptides must overcome several physiological barriers, including stomach acid, proteolytic enzymes, glutathione, the mucus layer, the epithelial barrier, and efflux. Size compounds the challenge. To illustrate, he notes that ibuprofen has a molecular weight of about 200 daltons, while peptides range from 1000 to 10,000 daltons.

Formulation technologies that address these barriers together are changing the outlook, however. For example, 3 oral peptides were approved in 2026, compared with about 4 in the past century, he emphasizes. He attributes the trend to more potent molecules and available delivery technologies.

How do lipid-based softgels deliver oral peptides?

Sukuru says softgels combined with lipid-based formulations can be matched to the peptide. For example, cyclic peptides can use an immediate-release shell while linear peptides prone to acid degradation can use an enteric shell that carries the payload to the duodenum or intestine.

"The lipids actually protect the peptides from aqueous degradation, like glutathione, which requires [an] aqueous environment, or proteolytic enzymes, which require [an] aqueous environment," Dr Sukuru says.

Vehicle selection also matters, he adds. Long-chain triglycerides can help prevent liver degradation. Fatty acids convert into permeation enhancers during digestion, promoting absorption at the epithelial surface. Formulations can also include mucolytic agents and efflux inhibitors.

Dr Sukuru also cites cyclosporine, a cyclic peptide needing no acid or enzyme protection, and voclosporin in an immediate-release softgel as approved examples. He notes that the softgel is a proven platform for peptide delivery.

AAPS 2026 PharmSci 360 runs October 25-28 in New Orleans. Attendees can visit Catalent at Booth 1811.

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About the speaker

Karunakar (Karu) Sukuru, RPh, PhD, Segment Vice President–Global Product Development & Innovation, Catalent Pharma Solutions

Dr Sukuru is a global pharmaceutical R&D leader with more than 30 years of experience in drug product development and advanced oral delivery technologies. In his current role, Dr Sukuru leads nearly 800 scientists across 14 international sites, driving innovation in the oral delivery of small-, mid-, and macromolecule therapeutics. A recognized expert in drug delivery and bioavailability-enabling technologies, Dr Sukuru holds 12 issued patents and has more than 15 pending across lyophilized biologics, nanoparticle systems, amorphous solid dispersions, and capsule-shell and fill-formulation science. Previous leadership roles include positions at Endo Pharmaceuticals and Banner Pharmacaps. Dr Sukuru is a frequent speaker at AAPS, CRS, FDA, and IPC forums and has served as an expert committee member at USP, contributing to standards-setting efforts. Dr Sukuru earned a master's degree and PhD from IIT-BHU, India, and a B.Pharm. from Gulbarga University, India, and is also a licensed pharmacist.