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Physicochemical interactions between drugs and superdisintegrants
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2008 (English)In: Journal of Pharmacy and Pharmacology (JPP), ISSN 0022-3573, E-ISSN 2042-7158, Vol. 60, no 12, 1583-9 p.Article in journal (Refereed) Published
Abstract [en]

We have evaluated the interactions between superdisintegrants and drugs with different physicochemical characteristics, which may affect the in-vivo absorption e.g. after mucosal administration. The binding of sodium salicylate, naproxen, methyl hydroxybenzoate (methylparaben), ethyl hydroxybenzoate (ethylparaben), propyl hydroxybenzoate (propylparaben), atenolol, alprenolol, diphenhydramine, verapamil, amitriptyline and cetylpyridinium chloride monohydrate (CPC) to different superdisintegrants (sodium starch glycolate (SSG), croscarmellose sodium (CCS) and crospovidone) and one unsubstituted comparator (starch) was studied spectrophotometrically. An indication of the in-vivo effect was obtained by measuring the interactions at physiological salt concentrations. SSG was investigated more thoroughly to obtain release profiles and correlation between binding and ionic strength. The results showed that the main interactions with the anionic hydrogels formed by SSG and CCS were caused by ion exchange, whereas the neutral crospovidone exhibited lipophilic interactions with the non-ionic substances. The effect of increased ionic strength was most pronounced at low salt concentrations and the ion exchange interactions were almost completely eradicated at physiological conditions. The release profile of diphenhydramine was significantly affected by the addition of salt. It was thus concluded that the choice of buffer was of great importance for in-vitro experiments with ionic drugs. At physiological salt concentrations the interactions did not appear to be strong enough to influence the in-vivo bioavailability of any of the drug molecules.

Place, publisher, year, edition, pages
2008. Vol. 60, no 12, 1583-9 p.
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97565DOI: 10.1211/jpp/60.12.0003ISI: 000261475100003PubMedID: 19000362OAI: oai:DiVA.org:uu-97565DiVA: diva2:172560
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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