Here is a summary of the technologies used in the recent oral peptide products:
Commercial Products:
- Permeation Enhancers: This is the most common strategy for commercially available oral peptides. These chemicals temporarily loosen tight junctions in the intestinal lining, allowing peptide absorption. Examples include sodium caprylate (found in octreotide capsules) and cyclodextrins (used in some insulin formulations).
- Enteric Coating: This protects peptides from stomach acid until they reach the small intestine, where absorption is better. Many existing oral peptide drugs use this approach.
- Each tablet of RYBELSUS contains 3 mg, 7 mg or 14 mg of semaglutide and the following inactive ingredients: magnesium stearate, microcrystalline cellulose, povidone and salcaprozate sodium (SNAC). Salcaprozate sodium, also known as SNAC or sodium N-[8-(2-hydroxybenzoyl)amino] caprylate, is a synthetic N-acetylated amino-acid derivative of salicylic acid. It is a weak acid that displays amphiphilicity and surface activity. SNAC is one of the most widely used small molecules as a penetration enhancer for peptide delivery. (Orange Book Patent: 9278123, Expires on 12/16/2031).
- Mycapssa is a commercially available oral medication containing the active ingredient octreotide, a somatostatin analog used to treat acromegaly and other conditions. Its enteric coating on the capsule dissolves only in the small intestine's neutral to slightly alkaline pH, protecting the octreotide from the harsh acidic environment of the stomach, where it would be degraded. Mycapssa contains several inactive ingredients that act as solubilizers, absorption enhancers, facilitating octreotide's uptake through the intestinal wall - polyvinylpyrrolidone (PVP-12), sodium caprylate, glyceryl monocaprylate and glyceryl tricaprylate, polysorbate 80, it also has magnesium chloride and a gelatin capsule.
- Lupkynis is a relatively new medication used to treat lupus nephritis, an inflammatory kidney disease. Like many drugs, Lupkynis's active ingredient, voclosporin, has poor oral bioavailability. To ensure effective delivery, Lupkynis employs a combination of ingredients to address this challenge. It contains plyethylene glycol succinate (tocofersolan), polysorbate 40, medium-chain triglycerides, trace amounts of soya lecithin, it further has a softgel capsule and ethanol.
- BYLVAY is available for oral administration as oral pellets containing odevixibat sesquihydrate equivalent to 200 mcg or 600 mcg of odevixibat, and as capsules containing odevixibat sesquihydrate equivalent to 400 mcg or 1200 mcg of odevixibat, and the following excipients: hypromellose and microcrystalline cellulose. Following a single radiolabeled odevixibat 3 mg oral dose in healthy adults, 82.9% of the dose was recovered in feces (97% unchanged) and less than 0.002% in the urine.
- TRULANCE (plecanatide) is a guanylate cyclase-C (GC-C) agonist. Plecanatide is a 16 amino acid peptide. Plecanatide is an amorphous, white to off-white powder. It is soluble in water. TRULANCE tablets are supplied as 3 mg tablets for oral administration. The inactive ingredients are magnesium stearate and microcrystalline cellulose.
- MACRILEN (granules) for oral solution is macimorelin acetate, a synthetic growth hormone secretagogue receptor agonist. Each aluminum pouch of MACRILEN contains 60 mg of macimorelin, equivalent to 68 mg of macimorelin acetate, and the following inactive ingredients: lactose monohydrate, crospovidone, sodium stearyl fumarate, saccharin sodium and colloidal silicon dioxide.
Clinical Stage Technologies:
- Nanocarriers: Lipid-based capsules like liposomes and micelles can encase peptides, protecting them from enzymes and enhancing absorption. Nanoparticles also offer controlled release and targeting capabilities.
- Mucoadhesive and Gastro-retentive Systems: These formulations stick to the intestinal lining or slowly release the peptide, increasing contact time for absorption. Examples include mucoadhesive tablets and floating dosage forms.
- Cell-Penetrating Peptides: These short peptides can be attached to the target peptide, helping it cross cell membranes and enter the bloodstream.
- Probiotic Delivery Systems: Engineered bacteria can produce and deliver therapeutic peptides directly to the gut, potentially avoiding absorption challenges.
- Oral Microneedles: These tiny needles, often made of dissolving materials, pierce the mucosal lining and deliver peptides directly to underlying tissues, bypassing first-pass metabolism.
It's important to note that oral peptide delivery is still a challenging field, and most drugs rely on injections. However, these innovative technologies offer promising solutions for improving peptide bioavailability and expanding treatment options.
