Hossain M, Abramowitz W, Watrous B J, Szpunar G J, Ayres J W
College of Pharmacy, Oregon State University, Corvallis 97331.
Pharm Res. 1990 Nov;7(11):1163-6. doi: 10.1023/a:1015936426906.
Gastrointestinal (GI) transit data necessary as "baseline" or "control" information were collected using pigs as animal models preliminary to bioavailability studies of new sustained action formulations. Density and size effects of nondisintegrating dosage forms on GI transit were investigated. Initially, enteric-coated nondisintegrating magnesium hydroxide caplets (density, 1.5 g/ml; size, 19.6 x 9.5 mm; weight, 1.2 g) were utilized in seven pigs. Prolonged gastric residence (greater than 5 days) occurred in every case for this dosage form. Therefore, nondisintegrating caplets of three densities (1.25, 1.45, and 2.3 g/ml) and three different sizes (large, 20 x 10 mm; medium, 10 x 10 mm; small, 5 x 10 mm) were studied in two more pigs. Roentgenography was used to visualize passage of caplets through the GI tract. Heidelberg pH capsules (size, 8 x 20 mm; density, 1.61 g/ml) were also used in this study. Total GI transit times range from 2 to 33 days for 22 administrations of these nondisintegrating dosage forms. Pigs are found to not be an appropriate model for evaluating bioavailability of nondisintegrating controlled-release dosage forms because total GI transit time (especially gastric transit) is much too long.
在对新型长效制剂进行生物利用度研究之前，以猪作为动物模型收集作为“基线”或“对照”信息所需的胃肠道（GI）转运数据。研究了不崩解剂型对胃肠道转运的密度和尺寸影响。最初，在七头猪中使用了肠溶包衣的不崩解氢氧化镁胶囊（密度为1.5 g/ml；尺寸为19.6×9.5 mm；重量为1.2 g）。对于这种剂型，每例均出现胃内滞留时间延长（超过5天）的情况。因此，在另外两头猪中研究了三种密度（1.25、1.45和2.3 g/ml）和三种不同尺寸（大，20×10 mm；中，10×10 mm；小，5×10 mm）的不崩解胶囊。使用X射线照相术观察胶囊在胃肠道中的通过情况。本研究中还使用了海德堡pH胶囊（尺寸为8×20 mm；密度为1.61 g/ml）。这些不崩解剂型给药22次的胃肠道总转运时间为2至33天。发现猪不是评估不崩解控释剂型生物利用度的合适模型，因为胃肠道总转运时间（尤其是胃转运时间）太长。
