Evolution of the microstructure and the drug release upon annealing the drug loaded lipid-surfactant microspheres

Varun Kushwah, Diogo Gomes Lopes, Ioannis Koutsamanis, Harald Plank, Stefan Ardelean, Avik Sarkar, Andrew Prpich, Mary T. am Ende, Heather Frericks Schmidt, Pankaj Doshi, Sheri Shamblin, Peter Laggner, Amrit Paudel*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The present study investigates the drug release-governing microstructural properties of melt spray congealed microspheres encapsulating the drug crystals in the matrix of glyceryl behenate and poloxamer (pore former). The solid-state, morphology, and micromeritics of the microspheres were characterized, before and after annealing, using calorimetry, X-ray scattering, porosimetry, scanning electron microscopy, and, NMR diffusometry. The in vitro drug release from and water uptake by the microspheres were obtained. The extent and the rate of drug release from the microspheres increased with a high poloxamer content and at higher annealing temperature and RH. All the drug release profiles were describable using the Higuchi release kinetics pointing towards the diffusion controlled release, both before and after annealing. The annealing process led to the polymorphic conversion of lipid and the increase in the pore size, predominantly at a higher temperature and humidity and for a high poloxamer content. The poloxamer domain increased from an initial 300 nm, up to 2000 nm upon annealing. The water diffusion rate inside the annealed microsphere was twice as fast as for unannealed counterparts. The findings relate the overall phase and pore structure change of the microsphere to the increased drug release induced by annealing. This work serves as a basis for the rational understanding of the modification of the in vitro performance by annealing, a widely used post-process for solid lipid products.

Original languageEnglish
Article number105278
Number of pages15
JournalEuropean Journal of Pharmaceutical Sciences
Volume147
DOIs
Publication statusPublished - 2020

Keywords

  • Annealing
  • Diffusometry
  • Lipid polymorphism
  • Microsphere
  • Microstructure

ASJC Scopus subject areas

  • Materials Science(all)
  • Pharmaceutical Science

Fields of Expertise

  • Advanced Materials Science

Treatment code (Nähere Zuordnung)

  • Basic - Fundamental (Grundlagenforschung)

Fingerprint Dive into the research topics of 'Evolution of the microstructure and the drug release upon annealing the drug loaded lipid-surfactant microspheres'. Together they form a unique fingerprint.

Cite this