Isoniazid-loaded orodispersible strips: Methodical design, optimization and in vitro-in silico characterization

Int J Pharm. 2018 Aug 25;547(1-2):347-359. doi: 10.1016/j.ijpharm.2018.06.004. Epub 2018 Jun 5.

Abstract

Drug treatment remains the most effective global approach to managing and preventing tuberculosis. This work focuses on formulating and evaluating an optimized polyvinyl alcohol-polyethylene glycol based orodispersible strip containing isoniazid, a first-line anti-tubercular agent. A solvent casting method guided through a Taguchi experimental design was employed in the fabrication, optimization and characterization of the orodispersible strip. The optimized strip was physically amalgamated with a monolayer, uniformly distributed surface geometry. It was 159.2 ± 3.0 µm thick, weighed 36.9 ± 0.3 mg, had an isoniazid load of 99.5 ± 0.8%w/w, disintegration and dissolution times of 17.6 ± 0.9 s and 5.5 ± 0.1 min respectively. In vitro crystallinity, thermal measurements and in silico thermodynamic predictions confirmed the strip's intrinsic miscibility, thermodynamic stability and amorphous nature. A Korsmeyer-Peppas (r = 0.99; n > 1 = 1.07) fitted kinetics typified by an initial burst release of 49.4 ± 1.9% at 4 min and a total of 99.8 ± 3.3% at 30 min was noted. Ex vivo isoniazid permeation through porcine buccal mucosa was bi-phasic and characterized by a 50.4 ± 3.8% surge and 95.6 ± 2.9% at 5 and 120 min respectively. The strip was physicomechanically robust, environmentally stable and non-cytotoxic.

Keywords: Buccal absorption; Experimental design; Isoniazid; Monolayer film; Orodispersible strip; Tuberculosis.

MeSH terms

  • Animals
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacokinetics
  • Chemistry, Pharmaceutical / methods
  • Computer Simulation
  • Crystallization
  • Drug Carriers / chemistry*
  • Isoniazid / administration & dosage*
  • Isoniazid / chemistry
  • Isoniazid / pharmacokinetics
  • Mouth Mucosa / metabolism*
  • Polyethylene Glycols / chemistry
  • Polyvinyl Alcohol / chemistry
  • Solubility
  • Solvents / chemistry
  • Swine
  • Thermodynamics

Substances

  • Antitubercular Agents
  • Drug Carriers
  • Solvents
  • Polyethylene Glycols
  • Polyvinyl Alcohol
  • Isoniazid