Colon delivery efficiencies of intestinal pressure-controlled colon delivery capsules prepared by a coating machine in human subjects

Large quantities of pressure-controlled colon delivery capsules (PCDCs) wer e prepared by a Hicoater-mini pharmaceutical coating machine and colon deli very efficiencies were evaluated in man. Caffeine powder as a model drug wa s suspended with a polyethylene glycol (PEG) 1000 suppository base at 50 de greesC, and was hardened in no. 0- and no. 2-sized capsular shapes. The cap sule-shaped suppositories were coated with 5% w/v ethanolic ethylcellulose (7G grade) solution using the coating machine. By increasing the coating weight of ethylcellulose from 28.6 +/- 1.1 mg to 45.3 +/- 0.2 mg, the mean coating thickness of no. 0 PCDCs increased from 5 6 +/- 1 mum to 64 +/- 1 mum. With no. 2 PCDCs, the mean coating thickness i ncreased from 50 +/- 1 mum to 57 +/- 1 mum by increasing the coating weight of ethylcellulose from 8.1 +/- 0.5 mg to 11.2 +/- 0.3 mg. The no. 0 PCDCs, having a mean ethylcellulose coating membrane thicknesses of 56 +/- 1 mum (type 1) and 64 +/- 1 mum (type 2), as well as no. 2 PCDCs, having thicknes ses of 50 +/- 1 mum (type 3) and 57 +/- 1 mum (type 4), were used for in-vi vo evaluation in man. After oral administration of test preparations contai ning 75 mg of caffeine, saliva samples were obtained and salivary caffeine levels were measured by an HPLC method. The first appearance time, Ti, of c affeine in the saliva was used as a parameter for the estimation of the rel ease time of caffeine from PCDCs in the gastrointestinal tract. The mean Ti values of no. 0 PCDCs were 3.3 +/- 0.3 h for type-1 and 5.3 +/- 0.3 h for type-2 preparations while the mean Ti values of no. 2 PCDCs were 4-3 +/- 0. 5 h for type 3 and 5.3 +/- 0.3 h for type 4. There were good correlations b etween ethylcellulose coating membrane thicknesses and in-vivo Ti values. A colon arrival time of 5 h was reported in our subjects by gastrointestinal magnetomarkergraphy. PCDCs having a mean coating thickness of 64 +/- 1 mum for no. 0 capsules an d of 57 +/- 1 mum for no. 2 capsules were thought to deliver caffeine to th e human colon efficiently.