New preparation method of intestinal pressure-controlled colon delivery capsules by coating machine and evaluation in beagle dogs

摘要

A new method for preparing large amounts of pressure-controlled colon delivery capsules (PCDCs) which employs a pharmaceutical coating machine, Hicoater-mini, has been developed. In contrast to our original method for preparing PCDCs where the inner surfaces of gelatin capsule were coated with the water-insoluble polymer ethylcellulose (EC), PCDC were directly prepared by coating the capsular shaped suppositories with EC. As a model drug, fluorescein (FL) was used in this study. FL powder was suspended with the suppository base, polyethylene glycol (PEC) 1000, at 50 degrees C, and was hardened in the capsular shape the sizes of which were #0 and #2. The capsular shaped suppositories were coated with 5% w/v ethanolic EC (7G grade) solution by a coating machine. By increasing the coating time from 55 to 75 min, the mean coating thickness of #0 PCDCs increased from 141+/-7 to 211+/-4 mu m. In the case of #2 PDDCs, the mean coating thickness increased from 102+/-3 to 110+/-5 mu m by increasing the coating time from 35 min to 40 min. Several kinds of #0 PCDCs having the mean EC coating membrane thickness of 141+/-7 mu m (type 1), 166+/-4 mu m (type 2), 188+/-4 mu m (type 3), 211+/-4 mu m (type 4) as well as #2 PCDCs having thickness of 102+/-3 mu m (type 5) and 110+/-5 mu m (type 6) were used for in vivo evaluation using beagle dogs. After oral administration of the test preparations containing 30 mg of FL, blood samples were obtained from the jugular vein and plasma FL levels were measured. The first appearance time, T-i, of FL in the plasma was used as a parameter for the estimation of the release time of FL from PCDCs in the gastrointestinal tract. The mean T-i of #0 PCDCs were 2.3+/-0.5 for type 1, 3.3+/-0.5 for type 2, 4.8+/-1.0 for type 3 and 7.8+/-1.7 h for type 4 preparations while the mean T-i of #2 PCDCs were 3.2+/-0.4 for type 5 and 3.8+/-0.4 h for type 6, respectively. There were good correlations between EC coatings. (C) 1998 Elsevier Science B.V. All rights reserved. [References: 28]