Buccal transmucosal delivery of calcitonin in rabbits using thin-film composites.
OBJECTIVE
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 microg 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 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.
Cui
Zhengrong
Z
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082, USA.
Mumper
Russell J
RJ
D000278:Administration, Buccal; D000818:Animals; D001682:Biological Availability; D002116:Calcitonin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002118:Calcium / Q000097:blood; D004304:Dosage Forms; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits
D004304:Dosage Forms; D002116:Calcitonin; D002118:Calcium