Why Highly Potent Peptides Can Succeed with Low Oral Bioavailability

In the second segment of an interview with Karunakar Sukuru, RPh, PhD, segment vice president of global product development and innovation at Catalent Pharma Solutions, ahead of American Association of Pharmaceutical Scientists’s (AAPS) 2026 PharmSci 360 conference, Dr Sukuru discusses choosing between softgel and sublingual peptide dosage forms. He presented his talk, “Patient-Centric Oral Peptide Delivery Using Softgel and Lyophilized ODT Technologies,” at the conference during the symposium “Emerging Strategies for Oral Macromolecular Delivery” on Oct. 28, 2026.

Dr Sukuru says not every peptide can be delivered through the gastrointestinal (GI) route because of physiological barriers, particularly pH and proteolytic enzymes. Sublingual delivery avoids many of these barriers as the pH in the sublingual area is neutral, and proteolytic enzymes are absent, he explains.

Recent peptides are potent and substrate specific enough that high bioavailability is unnecessary, Dr Sukuru states. For example, an oral psoriasis peptide approved in March 2026 achieves about 0.1% to 0.3% bioavailability. Desmopressin, at about 1040 daltons, reaches about 1.65% bioavailability sublingually using a lyophilized tablet platform (Zydis, Catalent). Published work has experimentally delivered peptides above 4000 daltons, he adds.

How should developers choose between softgel and sublingual dosage forms?

Dr Sukuru notes that selection depends on a peptide's properties and the development goal. Orally dissolving tablets offer greater convenience for geriatric and pediatric patients and suit peptides needing modest bioavailability. Sublingual delivery may not work for large doses because the deliverable amount is limited. Those peptides may suit a lipid-based softgel, with or without an enteric shell, depending on whether the peptide is cyclic or linear.

"The oral delivery of peptides is clinically proven," Dr Sukuru emphasizes.

He notes that several approvals came this year, compared with 4 in the past century, and more products are in development, driven by patient convenience and compliance. He urges formulators to consider patient-centric drug product design and highly potent molecules, which do not require double- or triple-digit bioavailability.

AAPS 2026 PharmSci 360 runs October 25-28 in New Orleans.

Learn more insights from segment 1 of Dr Sukuru’s interview. Explore more conference coverage here.

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.