Oral peptide softgels use lipid fills and matched shells to carry fragile drugs through the gut

Oral peptide softgels are getting fresh attention as more peptide medicines move from the needle to the mouth. Karunakar Sukuru, who leads global product development and innovation at Catalent Pharma Solutions, explained how lipid filled soft capsules protect these molecules in an interview with BioPharm International before the AAPS PharmSci 360 meeting, held in New Orleans from 25 to 28 October. This explainer sets out the process step he described. It rests on a contract developer's own account, not on published trial data, and Catalent sells this service.

The barriers a swallowed peptide has to pass

A peptide taken by mouth meets a series of hazards before any of it reaches the blood. Sukuru listed stomach acid, enzymes that cut proteins apart, glutathione, the mucus layer that coats the gut, the layer of cells that lines it, and efflux, the pumps that push absorbed molecules back out. Size makes each step harder. He compared ibuprofen, a small molecule of about 200 daltons, with peptides that run from about 1,000 to 10,000 daltons. A molecule that large does not slip through the gut wall on its own. It needs help to cross, and it needs protection while it waits, because acid and enzymes start to break it down within the stomach and the upper intestine.

Sukuru said the field is changing because formulation tools now tackle several barriers at once. By his count, three oral peptides were approved in 2026, against about four over the whole previous century, and he credited more potent molecules alongside better delivery technology. We have not checked his tally against regulator lists, and he did not name the three products. The scale of the loss is clear from approved labels. The Rybelsus prescribing information puts the absolute bioavailability of that semaglutide tablet at about 0.4 to 1 percent. In plain terms, almost all of the peptide a patient swallows is lost before it can act, and that is the gap every oral format tries to narrow.

How a lipid softgel carries the peptide

The design starts with the shell, Sukuru said, and the shell is matched to the molecule. Cyclic peptides, which are naturally sturdier, can use an immediate release shell that opens in the stomach. Linear peptides that break down in acid can use an enteric shell, which stays closed until it reaches the duodenum or further along the intestine. Inside the shell sits a lipid based fill chosen for that peptide. "The lipids actually protect the peptides from aqueous degradation, like glutathione, which requires [an] aqueous environment, or proteolytic enzymes, which require [an] aqueous environment," he told the magazine. The logic is simple: the enzymes that attack a peptide work in water, so an oily fill keeps them away.

Inside the shell sits a lipid based fill chosen for that peptide.

The choice of oil, or vehicle, adds further jobs, according to Sukuru. Long chain triglycerides can help a drug avoid breakdown in the liver, he said. Fatty acids in the fill turn into permeation enhancers as the body digests them, which helps the peptide cross at the surface of the gut lining. Formulators can also add agents that thin mucus and compounds that block efflux pumps. As approved examples he cited cyclosporine, a cyclic peptide that needs no protection from acid or enzymes, and voclosporin in an immediate release softgel. He called the softgel a proven platform for peptide delivery. Both of his examples are cyclic molecules, and neither is a large metabolic peptide of the kind now driving demand.

What oral peptide softgels change on the plant floor

For manufacturing, the shift is in what surrounds the peptide rather than how the peptide is made. The drug substance is still built by chemical synthesis or in living cells and then purified, as our process coverage explains. What changes is the finished form: a capsule shell and an oily fill instead of a compressed tablet. The approved semaglutide tablets take a different route. Their label lists salcaprozate sodium, known as SNAC, as the absorption enhancer pressed in with the peptide. Both approaches aim at the same number, the share of drug that gets absorbed. Every gain there reduces the amount of peptide a maker has to synthesise and purify for each patient, which is often the costliest part of the chain.

That link gives oral peptide softgels a supply angle that goes beyond the clinic. Sukuru leads nearly 800 scientists across 14 sites, according to the magazine, which shows the scale at which Catalent offers oral development as a contract service. Catalent did not say which peptide programs use softgels, how many it has in development, or what output its capsule lines can reach. It also gave no absorption figures for its own peptide fills. Readers following how outside firms add capacity can track the contract maker deals we cover. For now, the interview describes a toolkit rather than a product, and the volume question stays open until a softgel peptide reaches late stage trials.

What the interview does not show

The account has clear limits. It is one company's view, given ahead of a conference where Catalent was exhibiting, and Sukuru speaks for a firm that sells softgel development. He is due to present a talk on softgel and freeze dried orally disintegrating tablet technology for oral peptides on 28 October, within a symposium on new strategies for oral macromolecular delivery. The interview gave no bioavailability numbers for any peptide in a lipid softgel, no comparison with tablets that use an enhancer, and no data on how stable the fill stays over a product's shelf life. Those are the figures a drug developer would need before choosing a format, and they are not public here.

What to watch is whether developers of new oral peptides pick capsules, enhancer tablets, or other formats, and whether any of them publish absorption data that beats the low single digit percentages seen on current labels. A format that lifted absorption by even a few points would change how much peptide the industry needs to produce. The opposite holds too. If oral products stay near today's absorption, wider use of pills would raise demand for drug substance well above what injections require, pushing more work onto synthesis and purification plants. Either way, the formulation choice made in a development lab will feed straight through to the size of the plants built to supply it.

Conclusion

Oral peptide softgels protect fragile molecules with a lipid fill and a shell matched to the peptide, according to Catalent's Karunakar Sukuru. Enteric shells can carry acid sensitive peptides past the stomach, and fatty acids can help them cross the gut wall. The interview offered no absorption data, and Catalent named no programs. The stakes are practical: current oral semaglutide absorbs about 1 percent or less, so any format that raises that share would cut the peptide makers must produce for each patient.