title: Combined UV/vis and micro-tomography investigation of acetaminophen dissolution from granules.
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.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Kašpar
authors.forename: Viola
authors.initials: V
authors.lastname: Tokárová
authors.forename: Sarang
authors.initials: S
authors.lastname: Oka
authors.forename: Koushik
authors.initials: K
authors.lastname: Sowrirajan
authors.forename: Rohit
authors.initials: R
authors.lastname: Ramachandran
authors.forename: František
authors.initials: F
authors.lastname: Štěpánek
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D002482:Cellulose / Q000737:chemistry; D004058:Diffusion; D005079:Excipients / Q000737:chemistry; D007700:Kinetics; D016062:Porosity; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility; D014057:Tomography, X-Ray Computed / Q000379:methods*; D014466:Ultraviolet Rays
chemical_list: D005079:Excipients; D000082:Acetaminophen; D002482:Cellulose; C109691:microcrystalline cellulose