Sustained release of diclofenac from polymer-containing suppository and the mechanism involved.
Sustained release of diclofenac sodium (DcNa) from suppositories composed of triglycerides and polymer was investigated by dissolution testing through an artificial membrane. DcNa was slowly released from a suppository containing carboxyvinyl polymer (CVP), and the extent of the release decreased with the amount of CVP added. Little effect was noted with the addition of other water-soluble polymers, such as hydroxyethylcellulose (HEC), xanthan gum, and polyvinylalcohol (PVA). When sodium benzoate was used instead of DcNa, a similar result was obtained with the addition of CVP. The result of release rate analysis together with the viscosity and pH in these cases showed that the reduction of solubility and diffusion due to sodium exchange between DcNa and CVP played an important role in the sustained release from the suppository. Also, in comparison with the results when CVP was not used, the plasma concentration profile of diclofenac after the administration of CVP suppository displayed a twofold longer half-life time.
Azechi
Y
Y
Formulation Development Laboratory, Eli Lilly Japan K. K., Hyogo, Japan.
Ishikawa
K
K
Mizuno
N
N
Takahashi
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D011108:Polymers; D051381:Rats; D013488:Suppositories; D013678:Technology, Pharmaceutical; D014783:Viscosity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D011108:Polymers; D013488:Suppositories; D004008:Diclofenac