Preparation, Characterization and In Vitro / In Vivo Evaluation of Oral Time-Controlled Release Etodolac Pellets

AAPS PharmSciTech. 2018 Feb;19(2):610-620. doi: 10.1208/s12249-017-0873-3. Epub 2017 Sep 15.

Abstract

The objective of this study was to prepare time-controlled release etodolac pellets to facilitate drug administration according to the body's biological rhythm, optimize the drug's desired effects, and minimize adverse effects. The preparation consisted of three laminal layers from center to outside: the core, the swelling layer, and the insoluble polymer membrane. Factors influenced the core and the coating films were investigated in this study. The core pellets formulated with etodolac, lactose, and sodium carboxymethyl starch (CMS-Na) were prepared by extrusion-spheronization and then coated by a fluidized bed coater. Croscarmellose sodium (CC-Na) was selected as the swelling agent, and ethyl cellulose (EC) as the controlled release layer. The prepared pellets were characterized by scanning electron microscopy and evaluated by a dissolution test and a pharmacokinetic study. Compared with commercial available capsules, pharmacokinetics studies in beagle dogs indicated that the prepared pellets release the drug within a short period of time, immediately after a predetermined lag time. A good correlation between in vitro dissolution and in vivo absorption of the pellets was exhibited in the analysis.

Keywords: etodolac; extrusion-spheronization; pellets; pharmacokinetics; time-controlled release.

MeSH terms

  • Administration, Oral
  • Animals
  • Cross-Over Studies
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / pharmacokinetics
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemical synthesis
  • Delayed-Action Preparations / pharmacokinetics
  • Dogs
  • Drug Evaluation, Preclinical / methods
  • Drug Implants / administration & dosage
  • Drug Implants / chemical synthesis*
  • Drug Implants / pharmacokinetics*
  • Etodolac / administration & dosage
  • Etodolac / chemical synthesis*
  • Etodolac / pharmacokinetics*
  • Excipients
  • Male
  • Random Allocation

Substances

  • Cyclooxygenase 2 Inhibitors
  • Delayed-Action Preparations
  • Drug Implants
  • Excipients
  • Etodolac