Formulation of spray-dried phenytoin loaded poly(epsilon-caprolactone) microcarrier intended for brain delivery to treat epilepsy

J Pharm Sci. 2007 May;96(5):1018-30. doi: 10.1002/jps.20935.

Abstract

This study evaluates the efficacy of the spray-drying technique in the bioengineering of phenytoin (PHT) containing poly(epsilon-caprolactone) (PCL) microcarrier intended for brain delivery for long-term treatment of epilepsy. Through orthogonally designed experiments, the optimal formulation and process variables for the preparation of PCL-microcarriers containing PHT were obtained. The produced microcarriers were characterized by coulter counter, scanning electron, scanning transmission electron microscopies, differential scanning calorimetry, powder X-ray diffraction, and in vitro release. The results showed that the produced microcarriers have a spherical structure, uniform size distribution, and a particle mean diameter of about 4.0 microm, which is suitable for brain delivery. The PHT was loaded as dispersed microcrystals within the PCL-microcarriers. From this system, PHT was released slowly into a buffer solution for approximately 14 days without any burst effect. These data suggested that PHT containing spray-dried PCL-microcarrier may be a promising drug delivery system for local brain delivery and long-term treatment of pharmacoresistant epilepsy.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / chemistry*
  • Brain / metabolism*
  • Calorimetry, Differential Scanning
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid
  • Crystallography, X-Ray
  • Delayed-Action Preparations
  • Desiccation*
  • Drug Carriers*
  • Drug Compounding
  • Emulsifying Agents / chemistry
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Microspheres*
  • Models, Chemical
  • Particle Size
  • Phenytoin / chemistry*
  • Phenytoin / metabolism
  • Polyesters / chemistry*
  • Powder Diffraction
  • Powders
  • Solubility
  • Surface Properties
  • Technology, Pharmaceutical / methods*
  • Time Factors
  • Water / chemistry

Substances

  • Anticonvulsants
  • Delayed-Action Preparations
  • Drug Carriers
  • Emulsifying Agents
  • Polyesters
  • Powders
  • Water
  • polycaprolactone
  • Phenytoin