Clinical study shows improved absorption of desmopressin with novel formulation.
OBJECTIVE
To create improved pharmaceutical formulations for nasal and sublingual administration of desmopressin and investigate their pharmacokinetic profiles in comparison with a commercial nasal liquid spray and finally to evaluate the volunteers' opinions on the different dosage forms.


METHODS
Both formulations were based on the characteristics of interactive mixtures. The nasal powder spray was produced by a rotary evaporator technique with sodium starch glycolate as carrier material and the sublingual tablet by direct compression after dry mixing with mannitol as carrier. The clinical study was an open-label, randomised cross-over pharmacokinetic study in healthy volunteers.


RESULTS
The nasal powder formulation gave a threefold increase in the absorption, unaltered time to maximum plasma concentration and a tendency to lower variability in the amount absorbed compared with the liquid spray. The powder was reported to be more irritating than the liquid but was still well accepted by the volunteers. The tablet did not improve the uptake of desmopressin, likely because of a poor disintegration sublingually.


CONCLUSIONS
The nasal powder formulation is a promising new dosage form for the delivery of desmopressin and other compounds. The sublingual tablet has a beneficial means of production and may be further developed by decreasing its disintegration time.
Fransén
Nelly
N
Department of Pharmacy, Uppsala University, P.O. Box 580, 75123 Uppsala, Sweden.
Bredenberg
Susanne
S
Björk
Erik
E
D000281:Administration, Intranasal; D000286:Administration, Sublingual; D000328:Adult; D050034:Antidiuretic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006490:Hemostatics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D055815:Young Adult
D050034:Antidiuretic Agents; D006490:Hemostatics; D003894:Deamino Arginine Vasopressin