Colon delivery capsule which disintegrates by inner pressure in the colon has been developed. Its efficiency was evaluated in beagle dogs using recombinant human granulocyte-colony stimulating factor(G-CSF) and 5-aminosalicylic acid (5-ASA) as model drugs. An oral gelatin capsule of which inside surface was coated with ethylcellulose (EC) was prepared for this purpose. Several kinds of EC-gelatin capsules having the thickness of EC layer from 46 to 221 μm, were prepared. As a content, propylene glycol solution containing polyoxyethylated, 60 μmol, castor oil derivative, citric acid and fluorescein, as an absorption marker, was fulfilled in the capsule. To measure the arrival time to the colon, the experiment using suifasalazine was performed. It was found that our new capsule arrived at the colon within 4∼5hr after oral administration. When EC capsule of thin thickness was administered to beagle dogs, it disintegrated within 2∼3hr after administration. In the case of 84 μm thickness capsule, it disintegrated within 4∼5hr after administration, which suggests its disintegration in the colon. After the administration of this capsule filled with G-CSF solution, 25 μg/kg, the maximum blood total leukocytes count (BTL) appeared at 10hr. Thereafter, the BTL count gradually decreased and returned to its normal level at 48hr. This result suggests the possibility of new oral dosage form of protein drug. Furthermore, after the administration of 5-ASA, 5-ASA began to appear in the blood at 4∼5hr after administration. With this dosage form, it will be easy to control the dosage of 5-ASA without suffering from the side effect of suifapyridine. Therefore, this new capsule is thought to be safe and useful for protein drugs and drugs for colonic disease.
