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Clinical study shows improved absorption of desmopressin with novel formulation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2009 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 26, no 7, 1618-1625 p.Article in journal (Refereed) Published
Abstract [en]

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. 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.   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.   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.

Place, publisher, year, edition, pages
2009. Vol. 26, no 7, 1618-1625 p.
Keyword [en]
clinical study, desmopressin, nasal administration, sodium starch glycolate, sublingual administration
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97566DOI: 10.1007/s11095-009-9871-9ISI: 000266585900007OAI: oai:DiVA.org:uu-97566DiVA: diva2:172561
Available from: 2008-10-03 Created: 2008-10-03 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Studies on a Novel Powder Formulation for Nasal Drug Delivery
Open this publication in new window or tab >>Studies on a Novel Powder Formulation for Nasal Drug Delivery
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nasal administration has potential for the treatment of indications requiring a fast onset of effect or for drugs with low oral bioavailability. Liquid nasal sprays are relatively common, but can be associated with suboptimal absorption from the nasal cavity; this thesis shows that nasal absorption can be significantly enhanced with a dry powder formulation.

It was shown that interactive mixtures, consisting of fine drug particles adhered to the surface of mucoadhesive carrier particles, could be created in a particle size suitable for nasal administration. Sodium starch glycolate (SSG), a common tablet excipient, was used as carrier material. In vitro evaluation of the formulation indicated that the mucoadhesion of the carrier was unlikely to be affected by the addition of a drug. The powder formulation did not improve the in vitro transfer of dihydroergotamine across porcine nasal mucosa compared with a liquid formulation; however, the results were associated with methodological shortcomings. The binding of model substances to SSG and three other excipients was evaluated. Ion exchange interactions were for example detected between SSG and cationic drugs, but these interactions were most extensive at low salt concentrations and should unlikely affect in vivo bioavailability at physiological salt concentrations. Absorption of the peptide drug desmopressin from the SSG nasal formulation, from a novel sublingual tablet formulation and from a commercial nasal liquid spray was evaluated in a clinical trial. While no improvement over the liquid spray was seen with the sublingual tablet, plasma concentrations after the nasal powder formulation were three times higher than those after the liquid spray. All formulations were well accepted by the volunteers. The use of currently available mucoadhesive carrier particles in interactive mixtures offers potential for a new method of producing nasal powder formulations that should also be applicable to large scale production.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 70 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 81
Keyword
nasal drug delivery, nasal powder spray, interactive mixture, mucoadhesion, sodium starch glycolate, superdisintegrant, bioavailability, clinical trial
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-9292 (URN)978-91-554-7288-7 (ISBN)
Public defence
2008-10-24, B41, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2008-10-03 Created: 2008-10-03 Last updated: 2009-05-06Bibliographically approved

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