Development of a Sustained Release Preparation of Diclofenac Sodium and its Pharmacokinetics in Dogs.

Abstract

Diclofenac sodium (DF-Na) is a phenylacetate non-steroidal anti-inflammatory agent, and has a good anti-inflammatory analgesic antipyretic effect. In this study, in consideration of daily variations in the severity of rheumatoid arthritis and osteoarthritis and to improve patient compliance, we developed sustained release preparations that are expected to be effective by a single daily administration. To select the most optimal preparation for humans, a pharmacokinetic study was performed in dogs. We employed multiple units for control of the drug release rather than a single sustained release system in the design of a sustained release preparation, and prepared four sustained release preparations with different sustained release mechanisms. 1. A preparation coated with a combination of enteric polymer (PMA) and water-insoluble polymer (EC) to delay the solubilization and water permeation of the film compared to those in the PMA-coated control preparation. 2. A preparation in which the drug granules are coated with an enteric film (PMA) combined with an organic acid (fumaric acid) to delay the release of DF-Na. 3. A preparation containing sustained release granules coated with a combination of water-insoluble polymer (EC) and water-soluble polymer (PVP) to make the drug release time-dependent. 4. A preparation double-coated with a water-insoluble film (EC: PVP = 2 : 1) and an enteric film (PMA) to delay the release of DF-Na. The four sustained release preparations with different mechanisms were selected based on the pharmacokinetic study in beagles for the next clinical study.