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| Azopolymer coating. The azo aromatic functionality in the polymer segment shown here (two additional segments exist in the compound) allows drug-loaded pellets to resist degradation in the stomach and small intestine but be readily absorbed in the large intestine. |
Proteolytic enzymes in the gastrointestinal tract convert foods that we eat into essential nutrients. But when protein- or peptide-based drugs, such as insulin, are administered orally, these same enzymes destroy the drug before it reaches its target. Avoiding this destruction has required less convenient and more expensive routes of administration, along with increased dosing schedules. Attempts have been made to shuttle orally administered drugs through the harsh environment of the stomach and small intestine to the less enzymatically active colon. They have mostly involved time-release and pH-dependent preparations, however, which are sensitive to diet, food intake, intestinal motility, and disease states.
Akira Yamamoto and colleagues from Kyoto Pharmaceutical University in Japan and Ono Pharmaceutical Co., Ltd. (Osaka, Japan), recently used polymer-coated pellets to carry two peptide drugs, insulin and (Asu1,7)eel-calcitonin, to the colon (J. Pharm. Sci. 2001, 90, 89–97). Polymers containing azo aromatic groups are not digested in the stomach and small intestine but are broken down by microbes in the large intestine. The researchers used an easily prepared straight-chain polymer, readily disintegrated by azoreductases in the large intestine, to coat pellets containing either insulin or (Asu1,7)eel-calcitonin.
After administering the drug-loaded pellets to rats, the researchers followed the drug’s progress through the digestive tract, finding that both drugs were relatively stable in the stomach and small intestine but readily degraded in the large intestine. The scientists also found an increase in plasma glucose and calcium levels after administration of insulin- and calcitonin-laden pellets, respectively. This indicated that the drug was released from the pellets and absorbed by the lining of the large intestine. When the absorption-enhancing compound camostat mesilate was included in the pellet formulation, the plasma level and pharmacological availability of each drug were significantly enhanced in a dose-dependent manner. These coated pellets may soon prove to be useful drug carriers, allowing oral administration of peptide drugs. “The . . . benefit of this method of drug administration,” says Yamamoto, “is that patients can easily take these pellets . . . at home, and they do not have to visit their hospital and clinic.” It can also potentially eliminate the fear of needle-panicked patients.
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