<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><p>Ketorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. In <italic>vitro</italic> hydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (<italic>V/V</italic>) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics. <italic>In vivo</italic> biological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.</p></abstract>

Ketorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. In vitro hydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics. In vivo biological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.

Ketorolac-dextran conjugates: Synthesis, <italic>in vitro</italic> and <italic>in vivo</italic> evaluation

Department of Pharmacology, M. G. M. Medical College, A. B. Road, Indore-452001, India

Department of Pharmacy, Shri G. S. Institute of Technology and Science, Indore-452003, India

School of Pharmacy, DAVV Indore-452017, India

Acta Pharmaceutica

Ketorolac-dextran conjugates: Synthesis,  and  evaluation

Ketorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous...

Ketorolac-dextran conjugates: Synthesis, in vitro and in vivo evaluation

Publié en ligne: 28 déc. 2007

Pages: 441 - 450

DOI: https://doi.org/10.2478/v10007-007-0035-3

Mots clés
ketorolak-dekstran konjugati, dekstranski nosač, protuupalni nesteroidni lijekovi

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