PEPTIDES & PROTEINS molecules makes them valuable for treating metabolic disorders , such as diabetes , cancer , autoimmune diseases and neurological conditions , driving increased investment in their research , characterisation , clinical trials and manufacturing .
The oral route is the most common for drug administration and oral solid dose ( OSD ) medications have long been the most prescribed dosage form in the world , as they offer benefits of storage , stability and ease of self-administration . OSD drugs account for 84 % of medications worldwide .
Achieving effective oral delivery of peptides could have a transformative impact on patient care and accessibility . That achievement remains a major challenge , but , with continued investment in peptides for oral delivery , the pharmaceutical industry can address longstanding permeability and bioavailability hurdles to bring peptides to patients faster .
Barriers to oral peptide delivery
Peptides , proteins and large molecules are being clinically tested for innovative treatments across modalities . However , larger molecules tend to have more absorption challenges than small molecule medications , which are more easily delivered in oral pill or tablet form . Formulating a protein and peptide drug for delivery through the gastrointestinal ( GI ) tract requires a multitude of strategies .
First , the dosage form must stabilise the drug , making it available to take orally . Secondly , proteins and peptides must be protected from the extreme acidity and pepsin activity in the stomach , as it can result in enzymatic and gastric acid degradation . Biopharmaceutical researchers must consider how they can keep these large molecules stable enough to be absorbed in the required quantity for the drugs to have significant therapeutic efficacy .
As the drug then moves through the intestine , it must be protected from the plethora of enzymes in the intestinal lumen . Membrane permeability is the final challenge , as researchers must look at the site of absorption to ensure that it can cross the intestinal membrane and then the basal membrane , for entry into the bloodstream . All these factors are key considerations when developing the right oral dosage form for protein , peptide , oligonucleotide and other large molecule drugs .
Figure 1 - Physiological barriers & permeability challenges in GI tract Source : Acta Pharmaceutica Sinica B 2021 ; 11 ( 8 ): 2416e2448
MAR / APR 2025 SPECCHEMONLINE . COM
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