Development and evaluation of diclofenac sodium thermorevesible subcutaneous drug delivery system

Int J Pharm. 2012 Dec 15;439(1-2):120-6. doi: 10.1016/j.ijpharm.2012.10.009. Epub 2012 Oct 17.

Abstract

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 (144 h). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Diclofenac / administration & dosage*
  • Diclofenac / chemistry*
  • Diclofenac / pharmacokinetics
  • Drug Delivery Systems*
  • Gels
  • Hypromellose Derivatives
  • Injections, Subcutaneous
  • Male
  • Methylcellulose / analogs & derivatives
  • Methylcellulose / chemistry
  • Poloxamer / chemistry
  • Polyethylene Glycols / chemistry
  • Rabbits
  • Temperature

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Gels
  • Poloxamer
  • Diclofenac
  • Hypromellose Derivatives
  • Polyethylene Glycols
  • Methylcellulose