Which characteristic makes a drug not suitable for buccal/sublingual administration?

• A. All of the above
• B. High molecular weight
• C. Polar
• D. High dose

Answer: (A)

Buccal and sublingual delivery works best when the drug can diffuse across a lipid-rich mucous membrane, so the drug needs to be small, fairly lipophilic, and not heavily ionized at saliva pH. The mucosa has limited surface area and a short residence time, so large or highly polar molecules don’t cross efficiently and won’t provide meaningful absorption.

A drug with high molecular weight diffuses slowly or not at all across the mucosa, limiting uptake. Polar compounds have poor membrane partitioning into the lipid-rich barrier, so their permeability is low. A high dose presents more drug than the mucosa can absorb in the available time, and the excess is typically swallowed and subjected to first-pass metabolism, reducing the amount that enters systemic circulation.

Thus, all of these characteristics would hinder suitability for buccal/sublingual administration.