Buccal transmucosal delivery of calcitonin in rabbits using thin-film composites

被引:33
作者
Cui, ZR [1 ]
Mumper, RJ [1 ]
机构
[1] Univ Kentucky, Coll Pharm, Div Pharmaceut Sci, Lexington, KY 40536 USA
关键词
Eudragit; Polycarbophil; calcium; wax; film; salmon calcitonin; mucoadhesive;
D O I
10.1023/A:1021462012442
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. Salmon Calcitonin (sCT) is used to treat hypercalcemia resulting from Paget's disease and osteoporosis. sCT is available either in a sterile injectable form or nasal spray. Alternative and more cost- effective dosage forms for the delivery of calcitonin are needed. We sought to deliver sCT transmucosally using a previously reported mucoadhesive bilayer thin- film composite (TFC) via the buccal route. Methods. Forty micrograms of salmon calcitonin (200- IU) was loaded on preformed TFCs. In vitro release of sCT from TFCs was monitored in phosphate- buffered saline (10 mM, pH 7.4) at 37degrees C. Female New Zealand White rabbits (n = 6) were dosed with 40 mug of sCT either by injection via the ear vein or by applying sCT- loaded TFCs directly on the buccal pouch. Blood was collected at various times, and the plasma sCT and calcium concentrations were quantified. WinNonlin(R) was used to determine the relevant pharmacokinetic parameters. Results. In vitro, over 80% of sCT was released from the TFCs within 240 min. Super Case- II transport was indicated as the primary release mechanism. Rabbits injected intravenously had C-max, Cls, Vss, and AUC(0-inf) values of 75.1 +/- 6.5 ng/mL, 20.7 +/- 3.3 mL/min, 637 +/- 141 mL, and 1925 +/- 237 ng* min/ mL, respectively. Rabbits dosed via the buccal route had C-max, Cls, and AUC(0-400) (min) values of 4.6 +/- 1.6 ng/ mL, 22.0 +/- 5.9 mL/ min, and 842.9 +/- 209.7 ng* min/ mL, respectively. The relative bioavailability for rabbits treated with the TFCs was 43.8 +/- 10.9% with a CV of 24.9%. The reductions in plasma calcium levels after administration of sCT by both the intravenous and buccal route were comparable. Conclusions. The TFCs effectively delivered therapeutically efficacious amounts of sCT across the buccal mucosa in rabbits.
引用
收藏
页码:1901 / 1906
页数:6
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