In-vitro release kinetics and stability of anticardiovascular drugs-intercalated layered double hydroxide nanohybrids

J Phys Chem B. 2009 Nov 12;113(45):15090-100. doi: 10.1021/jp905440e.

Abstract

We report the intercalation and characterization of pravastatin and fluvastatin drugs in Mg(II)/Al(III) layered double hydroxides (LDHs) to form novel nanohybrid hydroxides through the coprecipitation technique. powder X-ray diffraction, Fourier transform infrared spectroscopy, and thermal analysis techniques reveal that the drugs are accommodated within the brucite layers. Structural characterization, computed results, and atomic force microscopy image analysis demonstrate that the fluvastatin anions are attached with the brucite as a monolayer, whereas the pravastatin anions form a multilayer. The shift in the stretching frequency of carboxylate anion of statin drugs provides evidence that the drugs are electrostatically bonded to LDHs. X-ray diffraction and thermal analysis studies performed after keeping the nanohybrid particles at 75 +/- 10% relative humidity atmosphere, indicate their physical stability due to proper confinement of drugs within the layers. In-vitro release study of developed nanohybrid particles suggests that the significant reduction in release rate of fluvastatin anions from fluvastatin intercalated LDHs is due to its hydrophobic nature and it can be further controlled by varying the concentration in physiological medium. After release, the data were fitted to the dissolution-diffusion kinetic model. The mechanism of drugs diffusion in hydrophobic nanohybrid is probably due to heterogeneous diffusion via anion exchange, while in a hydrophilic nanohybrid, it is due to intraparticle diffusion via anion exchange with the anions in the physiological medium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / administration & dosage*
  • Anticholesteremic Agents / pharmacokinetics
  • Chemical Precipitation
  • Delayed-Action Preparations / chemistry*
  • Diffusion
  • Drug Carriers / chemistry
  • Drug Stability
  • Fatty Acids, Monounsaturated / administration & dosage
  • Fatty Acids, Monounsaturated / pharmacokinetics
  • Fluvastatin
  • Hydrophobic and Hydrophilic Interactions
  • Indoles / administration & dosage
  • Indoles / pharmacokinetics
  • Kinetics
  • Nanostructures / chemistry
  • Pravastatin / administration & dosage
  • Pravastatin / pharmacokinetics
  • Static Electricity

Substances

  • Anticholesteremic Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Fatty Acids, Monounsaturated
  • Indoles
  • Fluvastatin
  • Pravastatin