The preferred route of administration for pharmaceutical products has been oral ingestion.
Oral drug delivery
The
preferred route of administration for pharmaceutical products has been oral
ingestion. As a drug passes through the GI tract, it encounters different
environments with respect to pH, enzymes, electrolytes, fluidity, and surface
features, all of which can influence drug absorption. There is a great
varia-tion in the pH across the GI tract, which runs from the mouth to the
anus. The interdigestive migration of a drug or a dosage form is governed by GI
motility, wherein the drug is exposed to different pHs at different time
peri-ods. The stomach has an acidic pH, varying from 2 to 4. The acidic pH in
the stomach increases up to a pH of 5.5 at the duodenum. The pH then increases
progressively from the duodenum to the small intestine (a pH of 6–7) and
reaches a pH of 7–8 in the distal ileum. After the ileocecal junction, the pH
falls sharply to 5.6 and then climbs up to neutrality during transit through
the colon. Owing to the pH variation in the GI tract, pH-sensitive polymers
have been historically utilized as an enteric-coating material. Enteric-coated
products featuring pH-sensitive polymers include tables, capsules, and pellets
and are designed to keep an active substance intact in the stomach and then to
release it into the upper intestine.
Apart
from the pH, mucosal layer plays an important role in drug absorp-tion from the
lumen of the GI tract. Small intestine has large epithelial surface area, which
consists of mucosa, villi, and microvilli. Drug must first diffuse through the
unstirred aqueous layer, the mucous layer, and the glycocalyx (which is the
coating of the mucous layer) in order to reach the microvilli, which is the
apical cell membrane. The tight junction between the cell mem-branes of
adjacent epithelial cells acts as a major barrier to the intercellular passage
of drug molecules from the intestinal lumen to the lamina propria.
The
low oral bioavailability of peptide and protein drugs is primarily due to their
large molecular size and vulnerability to proteolytic degradation in the GI
tract. Most protein and peptide drugs are susceptible to rapid degradation by
digestive enzymes. Furthermore, most peptide and protein drugs are rather
hydrophilic and thus are poorly partitioned into epithelial cell membranes,
leading to their absorption across the GI tract through passive diffusion.
Various
delivery systems have been proposed to increase drug absorption from the colon
and ileum and minimize exposure of the drug to proteolytic enzymes. Enteric
coatings that delay drug release for a sufficient period of time have been used
to target both the ileum and colon. In addition, encap-sulation into polymeric
materials that are degraded by the human colonic microflora has been proposed
as a method to increase drug absorption from the intestine. Coadministration of
enzyme inhibitors and absorp-tion enhancers has shown some promise.
Encapsulation into erodible or biodegradable nanoparticles has been explained
as a way of protecting drugs from enzymatic degradation. Submicron-size
particles are absorbed through transcytosis by both enterocytes and M cells.
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