title: Evaluation of tablet formation of different lactoses by 3D modeling and fractal analysis.
abstract: The aim of this study was to use 3D modeling to differentiate not only among the four different types of lactose alpha-lactose monohydrate, spray-dried lactose, agglomerated lactose and lactose anhydrous but also between products from different manufacturers. Further "box-counting" fractal analysis of SEM images was done to gain additional information on tableting characteristics and tablet properties which can be found in the fractal structure. Twelve different materials from different manufacturers were analyzed for their powder-technological and physicochemical properties. They were tableted on an eccentric tableting machine at graded maximum relative densities and the recorded data, namely force, time, and displacement were analyzed by the 3D modeling technique. Tablet properties such as, elastic recovery, crushing force and morphology were analyzed. The results show that 3D modeling can precisely distinguish deformation behavior for different types of lactose and also for the same type of material produced with a slightly different technique. Furthermore, the results showed that the amorphous content of the lactose determined the compactibility of the material, which is due to a reversible exceeding of the glass transition temperature of the material. The three fractal dimensions DBW (box surface dimension), DWBW (pore/void box mass dimension), and DBBW (box solid mass dimension) are capable of describing morphological differences in lactose materials. Multivariate regression analysis showed that the fractal surface structure of the lactose-based materials is strongly correlated to tableting characteristics and tablet properties. Especially with regards to 3D modeling, it was found that the fractal indices can describe the parameters time plasticity d, pressure plasticity e, and fast elastic decompression, which is the inverse of omega. In addition, the 3D parameters are able to describe the powder and tablet fractal indices. In conclusion, the 3D modeling is not only able to characterize the compression process but it can also provide information on the final tablet morphology.
authors.affiliation: PLIVA-Research and Development Ltd., Pharmaceutical Technology, Prilaz baruna Filipovica, Zagreb, Croatia.
authors.forename: Z
authors.initials: Z
authors.lastname: Jelcic
authors.forename: K
authors.initials: K
authors.lastname: Hauschild
authors.forename: M
authors.initials: M
authors.lastname: Ogiermann
authors.forename: K M
authors.initials: KM
authors.lastname: Picker-Freyer
mesh_terms: D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004548:Elasticity; D005079:Excipients / Q000737:chemistry*; D017709:Fractals; D007785:Lactose / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008961:Models, Structural; D010316:Particle Size; D044367:Phase Transition; D012044:Regression Analysis; D012212:Rheology; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D044366:Transition Temperature
chemical_list: D005079:Excipients; D013607:Tablets; D007785:Lactose