Titre du document / Document title

Design of a water-soluble, solution-stable and biolabile prodrug of metronidazole for parenteral administration: N-substituted aminoethylbenzoate esters

Auteur(s) / Author(s)

JENSEN E. ⁽¹⁾ ; BUNDGAARD H. ; FALCH E. ;

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

⁽¹⁾ Royal Danish school pharmacy, dep. pharmaceutical organic chemistry, Copenhagen 2100, DANEMARK

Résumé / Abstract

Various N-substituted aminomethylbenzoate esters of metronidazole were synthesized and evaluated as water-soluble prodrugs with the aim of developing preparations suitable for intravenous injection. The esters showed all a high solubility in weakly acidic solutions and were further characterized by possessing a high stability in such solutions allowing long-term storage combined with a high susceptibility to undergo enzymatic hydrolysis in plasma. These compounds (the 4-(morpholinomethyl)benzoate and 3-[(4-methylpiperazin-1-yl)methyl] benzoate esters) were predicted to possess shelf-lives of more than 10 years in aqueous solution of pH 4.0 and at 25^oC. These properties regarding solubility, chemical stability and enzymatic lability make N-substituted aminomethylbenzoate esters a promising new prodrug type for metronidazole as well as for other slightly soluble drugs containing an esterifiable hydroxyl group

Revue / Journal Title

International journal of pharmaceutics   ISSN 0378-5173   CODEN IJPHDE 

Source / Source

1990, vol. 58, n^o2, pp. 143-153 (14 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1978) (Revue)

Mots-clés anglais / English Keywords

Prodrug ; Antibiotic ; Parasiticid ; Stability ; Preparation ; Solubility ; Kinetic parameter ; Pharmaceutical technology ;

Mots-clés français / French Keywords

Promédicament ; Métronidazole ; Antibiotique ; Antiparasitaire ; Stabilité ; Préparation ; Solubilité ; Paramètre cinétique ; Technologie pharmaceutique ; Hydrolyse enzymatique ;

Mots-clés espagnols / Spanish Keywords

Promedicamento ; Antibiótico ; Antiparasitario ; Estabilidad ; Preparación ; Solubilidad ; Parámetro cinético ; Tecnología farmacéutica ;

Localisation / Location

INIST-CNRS, Cote INIST : 16510, 35400000764077.0080