The effect of granule microstructure on dissolution rate

• Published in: Powder technology Vol. 181; no. 2; pp. 104 - 114
• Main Authors: Ansari, Mansoor A., Stepanek, Frantisek
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Lausanne Elsevier B.V 06.02.2008; Elsevier
• Subjects: Applied sciences; Chemical engineering; Computer simulation; Dissolution; Exact sciences and technology; Granulation; Microstructure; Miscellaneous; Porosity; Product design; Sintering, pelletization, granulation; Solid-solid systems; Product design; Porosity; Granulation; Computer simulation; Microstructure; Dissolution; Correlation; Mixing; In situ; Agglomeration; Binders; Design; Particle size distribution; Correlation analysis; Tomography; Numerical simulation; Product development; Granule; Computer aid
• ISSN: 0032-5910; 1873-328X
• DOI: 10.1016/j.powtec.2006.12.012

The relationship between the microstructure of granules and their dissolution rate has been investigated. Granules consisting of mannitol primary particles and PVP aqueous binder have been prepared by top-spray fluid-bed granulation, and granules consisting of sucrose primary particles and PEG binder by in-situ melt fluid-bed granulation. Granule microstructure has been systematically varied by manipulating the primary particle size distribution and the binder content in each case. In both cases granule porosity was found to be a decreasing function of binder content and a minimum of porosity as function of the fine/coarse primary particle mixing ratio has been observed, in line with theoretical expectations. Granule microstructures have been analysed using X-ray computed micro-tomography and compared with three-dimensional “virtual granules” generated by a computer simulation of the agglomeration process. The dissolution rate of granules has then been measured. While porosity was found to have a strong effect on the dissolution rate of mannitol granules, the dissolution rate was found to be practically independent of porosity in the case of sucrose granules. The formulation–microstructure and microstructure–dissolution correlations established in course of this work are in line with previous computer simulation results and form part of a computer-aided granule design methodology. The relationship between the microstructure of mannitol-PVP and sucrose-PEG granules and their dissolution rate has been investigated. Microstructures have been analysed by X-ray computed micro-tomography and compared with three-dimensional “virtual granules” generated by a computer simulation of the agglomeration process. Granule porosity was found to be a decreasing function of binder content and a minimum of porosity as function of the fine/coarse primary particle mixing ratio has been observed. [Display omitted]