Preparation and characteristics of thermoresponsive gel of minocycline hydrochloride and evaluation of its effect on experimental periodontitis models

Drug Deliv. 2016;23(2):525-31. doi: 10.3109/10717544.2014.929195. Epub 2014 Jun 25.

Abstract

In this study, a thermoresponsive gel for minocycline (MCL) with chitosan/β-glycerophosphate (C/β-GP) was formulated and its characterization, in vitro release, stability, toxicity and pharmacodynamics were investigated. The formulation containing MCL was prepared by pouring the chitosan solution directly onto the sterilized drug powder and stirring before mixing with the β-glycerophosphate (β-GP) solution. The final preparations contained 0.5% (w/v) chitosan, 1.8% (w/v) β-GP and 2% (w/v) MCL. The drug content of prepared gels was in the range of 92-99%, and the pH value of the optimized formulation was found to be 5.6-6.2. The gelation temperature of the prepared C/β-GP thermogelling solutions was 37 °C. Color, consistency, pH, viscosity and drug content of the in situ gels were found to be consistent, and no signs of separation and deterioration were observed over a period of 90 d. In vivo studies showed that rats' liver and kidney tissue sections were normal, with no structural damage. The constituents of the in situ gels formulation had a well-sustained release efficacy on the animal model of periodontitis.

Keywords: Chitosan/β-glycerophosphate; minocycline; model of periodontitis; thermoresponsive gel.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / toxicity
  • Bacteroidaceae Infections / drug therapy*
  • Bacteroidaceae Infections / microbiology
  • Chitosan / chemistry*
  • Chitosan / toxicity
  • Delayed-Action Preparations
  • Disease Models, Animal
  • Drug Carriers*
  • Drug Compounding
  • Drug Stability
  • Female
  • Gels
  • Glycerophosphates / chemistry*
  • Glycerophosphates / toxicity
  • Hydrogen-Ion Concentration
  • Kinetics
  • Male
  • Minocycline / administration & dosage*
  • Minocycline / chemistry
  • Minocycline / toxicity
  • Periodontal Pocket / drug therapy
  • Periodontal Pocket / microbiology
  • Periodontitis / drug therapy*
  • Periodontitis / microbiology
  • Porphyromonas gingivalis / drug effects
  • Porphyromonas gingivalis / growth & development
  • Rats, Sprague-Dawley
  • Solubility
  • Technology, Pharmaceutical / methods
  • Temperature*
  • Viscosity

Substances

  • Anti-Bacterial Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Gels
  • Glycerophosphates
  • Chitosan
  • Minocycline
  • beta-glycerophosphoric acid