Improved nasal bioavailability of elcatonin by insoluble powder formulation.
The bioavailability of elcatonin (ECT) via the nasal route was investigated with a powder dosage form utilizing water-insoluble calcium carbonate (CaCO(3)) in comparison with the liquid dosage form. Total radioactivity and the radioactivity of intact [3H]ECT were measured to evaluate the nasal absorption in vivo and the nasal mucosal transport in vitro. The systemic bioavailability of both total radioactivity and intact [3H]ECT following intranasal administration of the powder formulation in rats was significantly greater than in the case of the liquid formulation. In contrast, similar permeability of ECT across excised rabbit nasal mucosa was seen for both formulations, and was close to that of [14C]inulin, suggesting that the ECT transport is predominantly paracellular in each case. However, the powder formulation significantly prolonged the residence time of [3H]ECT in the rat nasal cavity, compared with the liquid formulation. We conclude that the powder formulation utilizing CaCO(3) improves the nasal bioavailability by increasing the residence time of ECT in the nasal cavity and is likely to be effective in increasing systemic drug delivery.
Ishikawa
F
F
Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.
Katsura
M
M
Tamai
I
I
Tsuji
A
A
D000281:Administration, Intranasal; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002116:Calcitonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D002118:Calcium / Q000097:blood; D002119:Calcium Carbonate / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism; D010539:Permeability; D011208:Powders; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium / Q000737:chemistry
D011208:Powders; D014316:Tritium; D002116:Calcitonin; D002119:Calcium Carbonate; D002118:Calcium; C012755:elcatonin