Comparative in vitro and in vivo evaluations of oral sustained-release formulations of diclofenac sodium in beagle dogs.
OBJECTIVE
Two sustained release formulations (microspheres and Voltaren SR75) were evaluated for their drug release characteristics in dissolution (in vitro study) and after oral administration to beagle dogs (in vivo study) by HPLC.


METHODS
The dissolution study was carried out according to the paddle method and the pharmacokinetic study was conducted using HPLC analysis in a crossover design in six female beagle dogs after oral administration of 75 mg diclofenac sodium (DFS).


RESULTS
The dissolution profiles showed 45% release for Voltaren SR75 and around 95% for the microspheres. Oral administration of DFS resulted in AUC(0-24) and Cmax values of 20.4 microg h/mL and 3.04 microg/mL for microspheres and 33.5 microg h/mL and 5.59 microg/mL for Voltaren, respectively. The Tmax was 3.0 h for both formulations. A significant difference in AUC(0-24) and Cmax was observed for DFS absorption from microspheres and Voltaren.


CONCLUSIONS
The results from the dissolution assay demonstrated the faster release of diclofenac sodium from microspheres. The bioavailability of DFS in microspheres was about 61% that of Voltaren, for the parameters AUC and Cmax, and they are therefore not bioequivalent to Voltaren in relation to the extent of absorption. However, the rate of drug absorption (Tmax) was similar for the two formulations.
Medeiros
D C
DC
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brasil.
Mazon-Cardoso
T
T
Lemos-Senna
E
E
Poli
A
A
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004285:Dogs; D005260:Female; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D008863:Microspheres; D015203:Reproducibility of Results; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004008:Diclofenac