Oral drug delivery

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.