Combined UV/vis and micro-tomography investigation of acetaminophen dissolution from granules

Ondřej Kašpar, Viola Tokárová, Sarang Oka, Koushik Sowrirajan, Rohit Ramachandran, František Štěpánek

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The X-ray micro-tomography (micro-CT) technique has been used to visualize the microstructure of granules produced by high shear wet granulation and the dynamic evolution of porosity during granule dissolution. Using acetaminophen (paracetamol) as the active pharmaceutical ingredient (API) and microcrystalline cellulose (Avicel PH-200) as an excipient, the porosity of the granules was systematically influenced by the granulation process parameters (binder/solids ratio, impeller speed and wet massing time). An increase of granule porosity from 7% to 10% and 18% lead to a decrease of the dissolution time t90 from 435 min to 98 min and 37 min, respectively. The combination of time-resolved micro-CT imaging with UV/vis detection of the quantity dissolved made it possible to evaluate the effective diffusion coefficient of the API through the granule structure, and thus establish a quantitative structure-property relationship for dissolution. A power-law dependence of the effective diffusivity on porosity (Archie's law) was found to hold.

Original languageEnglish (US)
Pages (from-to)272-281
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume458
Issue number2
DOIs
StatePublished - 2013

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Diffusion
  • Dissolution
  • Granulation
  • Micro-CT
  • Microstructure
  • Porosity

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