Development and evaluation of diclofenac sodium thermorevesible subcutaneous drug delivery system

• Published in: International journal of pharmaceutics Vol. 439; no. 1-2; pp. 120 - 126
• Main Authors: Nasir, Fazli, Iqbal, Zafar, Khan, Jamshaid A., Khan, Abad, Khuda, Fazli, Ahmad, Lateef, Khan, Amirzada, Khan, Abbas, Dayoo, Abdullah, Roohullah
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-12-2012
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; autoclaving; blood; computer software; Diclofenac - administration & dosage; Diclofenac - chemistry; Diclofenac - pharmacokinetics; Diclofenac sodium; Drug Delivery Systems; drugs; Gels; Hypromellose Derivatives; Injections, Subcutaneous; Male; mathematical models; Methyl cellulose; methylcellulose; Methylcellulose - analogs & derivatives; Methylcellulose - chemistry; pharmacokinetics; Pluronics; Poloxamer - chemistry; polyethylene glycol; Polyethylene Glycols - chemistry; Rabbits; sodium; Subcutaneous; subcutaneous injection; Temperature; Thermoreversible in situ gels; viscosity; Diclofenac sodium; Thermoreversible in situ gels; Pluronics; Subcutaneous; Methyl cellulose
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2012.10.009

Plasma concentration (μg/ml) of diclofenac sodium at various time intervals after subcutaneous injection of commercial diclofenac sodium injection and DS in situ gels.
The objective of current work was to develop and evaluate thermoreversible subcutaneous drug delivery system for diclofenac sodium. The poloxamer 407, methyl cellulose, hydroxypropyl methyl cellulose and polyethylene glycol were used alone and in combination in different ratios to design the delivery system. The physical properties like Tsol–gel, viscosity, clarity of solution and gel were evaluated. The in vitro release of the drug delivery system was evaluated using membrane less method and the drug release kinetics and mechanism was predicted by applying various mathematical models to the in vitro dissolution data. Rabbits were used as in vivo model following subcutaneous injection to predict various pharmacokinetics parameters by applying Pk-Summit software. The in vitro and in vivo data revealed that the system consisting of the poloxamer 407 in concentration of 20% (DP20) was the most capable formulation for extending the drug release and maintaining therapeutic blood level of DS for longer duration (144h). The data obtained for drug content after autoclaving the solutions indicate that autoclaving results in 6% degradation of DS. The data also suggested that the studied polymers poloxamer, MC and PG are good candidate to extend the drug release possessing a unique thermoreversible property.