Comparative study of in-vitro release and bioavailability of sustained release diclofenac sodium from certain hydrophilic polymers and commercial tablets in beagle dogs

• Published in: Pharmaceutica acta Helvetiae Vol. 72; no. 3; pp. 159 - 164
• Main Authors: Hosny, Ehab A., Al-Helw, Abdel Raheem M., Al-Dardiri, Mohammad A.
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01-06-1997
• Subjects: Alginates; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Beagle dogs; Bioavailability; Biological Availability; Carboxymethylcellulose Sodium; Commercial tablets; Delayed-Action Preparations; Diclofenac - administration & dosage; Diclofenac - chemistry; Diclofenac - pharmacokinetics; Diclofenac sodium; Dogs; Drug Carriers; Glucuronic Acid; Hexuronic Acids; Hydrophilic polymers; In-vitro release; Male; Sustained release; Tablets, Enteric-Coated; Hydrophilic polymers; Beagle dogs; Diclofenac sodium; Commercial tablets; Sustained release; In-vitro release; Bioavailability
• ISSN: 0031-6865
• DOI: 10.1016/S0031-6865(97)00010-1

Hydrophilic colloids interact with metallic ions to yield crosslinked insoluble salts. Such principle was utilized in the preparation of diclofenac sodium beads from sodium alginate and sodium carboxymethylcellulose. Hard spherical beads of aluminum alginate and aluminum carboxymethylcellulose with a narrow particle size distribution (1.60 ± 0.12 and 3.10 ± 0.20 mm) and low friability (0.5 and 1.4%) respectively were obtained with high yield (80–90%) and a drug content approaching 70–80%. The type and concentration of the polymers as well as the pH of the dissolution medium were found to affect the rate of drug release. Beads prepared from Na-alginate showed a non-significantly (p >; 0.05) faster rate of drug release than that prepared from NaCMC. The higher the polymer concentration, the slower was the rate of drug release. Diclofenac sodium did not release in 0.1 N HC1 (pH 1.2) for 2 h and released in phosphate buffer solution (pH 6.8) from the two formulations studied and from the commercial Voltaren Retard tablet. The two formulations of the beads resulted in a sustained release action of diclofenac sodium for 24 h. They showed Kel values of 0.02 ± 0.01 and 0.3 ± 0.01 h −1 and these correspond to t12 of 34.65 and 27.70 for the Na-alginate and NaCMC beads, respectively. They also showed mean residence time (MRT) values of 9.56 ± 2.5 and 7.86 ± 0.54 h, respectively. They also showed non-significant (p >; 0.05) differences with respect to their plasma levels, Cmax, Tmaxand AUC0 → 24h. The relative bioavailability of the two formulations were 59.01 and 47.96%, respectively, relative to that of the commercial Voltaren Retard tablets of Ciba-Geigy which showed a Kelof 0.044 h −1 corresponding to a t12of 15.75 handMRTof 7.45 ± 1.10 h.