A quiet analytical research laboratory at night, racks of glass vials along a dim bench.

Delivery Challenges Library

A compound can be potent in a dish and useless in a capsule. This library explains the eleven barriers that most often separate a molecule from a working product, what each one does in the body, and which encapsulation strategies address it. Each page is written for formulation scientists and business development teams screening an active.

Barriers in the gut

Five pages cover the oral route in the order a compound meets them. Stomach acid degradation covers acid-labile actives. Protease degradation covers peptides attacked by pepsin, trypsin and brush-border peptidases. Poor water solubility covers actives that never dissolve enough to be absorbed. Poor membrane permeability covers molecules too large or polar to cross the epithelium, and efflux transporters covers P-glycoprotein pumping compounds back into the gut lumen. Most oral actives meet at least two of these five barriers in sequence.

Barriers after absorption

First-pass metabolism explains why compounds that are absorbed well still reach the circulation in small fractions, as with resveratrol and NAC. Short half-life and rapid clearance covers molecules such as native GLP-1 that last minutes in plasma and explains which extension strategies are chemical and which are formulation-based. Oxidation and instability covers losses on the shelf and in the body for thiols, polyphenols, carotenoids and vitamin C. Several of these losses can be avoided entirely by choosing a different route.

Barriers of format and use

Bitter taste and palatability covers why actives such as berberine and NAC are hard to put in liquids and chewables. Skin barrier penetration covers the stratum corneum and the 500 Da rule for topical and transdermal formats. Injection burden covers the adherence and access cost of injectable therapies and which needle-free alternatives are realistic today. These barriers decide whether a product is used consistently, which matters as much as how much of it is absorbed.

Key facts

  • Roughly 40% of marketed drugs and up to 90% of pipeline candidates have poor aqueous solubility (Kalepu and Nekkanti 2015, Acta Pharm Sin B)
  • Resveratrol is about 70% absorbed orally but has near-zero bioavailability of the parent compound due to rapid metabolism (Walle et al. 2004, Drug Metab Dispos)
  • Native GLP-1 has a plasma half-life of about 2 minutes due to DPP-4 cleavage (Deacon et al. 1995, Diabetes)
  • P-glycoprotein limits oral absorption of many substrates by active efflux (Lin and Yamazaki 2003, Clin Pharmacokinet)

How our delivery technology applies

Most real actives hit more than one barrier, which is why a single-function carrier often disappoints. Multi-layer encapsulation assigns a layer to each barrier in the order the compound meets them: storage protection innermost, then permeation support, then enzyme shielding, then acid resistance outermost. Each challenge page states which layer functions apply and where the limits of encapsulation are.

Screen your active against these barriers with the Formulation Finder.

Poor Water Solubility

If an active does not dissolve in gut fluid, it cannot be absorbed, no matter how permeable it is.

Protease Degradation of Peptides

The digestive tract is designed to cut proteins into amino acids, and it does not distinguish a therapeutic peptide from a meal.

Related reading

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