Titre du document / Document title

Interaction of naproxen with ionic cyclodextrins in aqueous solution and in the solid state

Auteur(s) / Author(s)

MURA P. ⁽¹⁾ ; FURLANETTO S. ⁽¹⁾ ; CIRRI M. ⁽¹⁾ ; MAESTRELLI F. ⁽¹⁾ ; CORTI G. ⁽¹⁾ ; PINZAUTI S. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Dipartimento di Scienze Farmaceutiche, Università di Firenze, Polo Scientifico di Sesto Fiorentino, 50019 Sesto Fiorentino, Firenze, ITALIE

Résumé / Abstract

The possible role of the cyclodextrin charge in the interaction with an acidic drug such as naproxen (pK_a 4.8) has been evaluated. Sulfobutylether-B-cyclodextrin (SBE-BCyd) and trimethylammonium-B-cyclodextrin (TMA-βCyd) were selected as, respectively, anionically and cationically charged carriers and their performance was compared with that of the parent β-cyclodextrin (βCyd) and of its methyl-derivative (MeBCyd) previously found as the best partner for the drug. Interactions in solution were investigated by phase-solubility, fluorescence and circular dichroism analyses. Equimolar drug-carrier products prepared by different techniques (blending, cogrinding, sealed-heating, colyophilization) were characterized by differential scanning calorimetry and X-ray powder diffractometry and tested for drug dissolution properties. Anionic charges of SBE-βCyd did not negatively influence interactions in unbuffered aqueous solutions (pH5) with the acidic drug. In fact, it was a very effective carrier, exhibiting solubilizing and complexing properties considerably better than the parent βCyd and comparable to those of MeBCyd. On the contrary, the positive charges of TMA-βCyd did not favour interactions with the counter-ionic drug (despite the presence of about 60% ionised drug) and it was less efficacious also than native BCyd. Therefore, the role of the Cyd charge on the complexing and solubilizing properties towards naproxen was not important whereas other factors, such as steric hindrance effects and favourable hydrophobic interactions were significant in determining the drug affinity for the Cyd inclusion. Solid state studies evidenced similar amorphizing properties of both charged Cyds towards naproxen. On the other hand, dissolution tests, in agreement with solution studies, showed that all products with SBE-BCyd exhibited significantly better dissolution properties than the corresponding ones with TMA-BCyd. A clear influence of the preparation method of drug-Cyd solid systems on the performance of the end product was also observed. Colyophilization was the most effective technique, followed by the cogrinding one. Colyophilized product with SBE-BCyd allowed a 10-times increase in drug dissolution efficiency (D.E.) (with respect to the five-times increase obtained with the corresponding coground product) and a reduction of t_50% from about 60 min (for the coground product) to less than 2 min.

Revue / Journal Title

Journal of pharmaceutical and biomedical analysis   ISSN 0731-7085   CODEN JPBADA 

Source / Source

Congrès
PBA 2004 International Symposium on Pharmaceutical and Biomedical Analysis N^o15, Florence , ITALIE (02/05/2004)
2005, vol. 37, n^o 5 (360 p.)  [Document : 8 p.] (23 ref.), pp. 987-994 [8 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1983) (Revue)

Mots-clés anglais / English Keywords

Enzyme ; Oxidoreductases ; Prostaglandin-endoperoxide synthase ; Enzyme inhibitor ; Arylpropionic acid derivatives ; Non steroidal antiinflammatory agent ; Analgesic ; Antipyretic ; Dissolution ; Aqueous solution ; Cyclodextrin ; Naproxen ; Interaction ;

Mots-clés français / French Keywords

Enzyme ; Oxidoreductases ; Prostaglandin-endoperoxide synthase ; Inhibiteur enzyme ; Arylpropionique acide dérivé ; Antiinflammatoire non stéroïde ; Analgésique ; Antipyrétique ; Dissolution ; Solution aqueuse ; Cyclodextrine ; Naproxène ; Interaction ;

Mots-clés espagnols / Spanish Keywords

Enzima ; Oxidoreductases ; Prostaglandin-endoperoxide synthase ; Inhibidor enzima ; Arilpropionico ácido derivado ; Antiinflamatorio no esteroide ; Analgésico ; Antipirético ; Disolución ; Solución acuosa ; Ciclodextrina ; Naproxeno ; Interacción ;

Mots-clés d'auteur / Author Keywords

Naproxen ; Trimethylammonium-B-cyclodextrin ; Sulfobutylether-B-cyclodextrin ; Circular dichroism ; Fluorescence ; Dissolution ;

Localisation / Location

INIST-CNRS, Cote INIST : 19962, 35400012540382.0220