On the Breakage of High Aspect Ratio Crystals in Filter Beds under Continuous Percolation.

PURPOSE: This work details experimental observations on the effect of liquid flow percolating through packed beds of crystals to elucidate how the filtration pressure severely alters the size distribution and crystal shape. Pressure filtration is widely used in the pharmaceutical industry, and frequently results in undesired size distribution changes that hinder further processing. METHODS: The percolation methodology presented fixes fluid flow through a bed of crystals, resulting in a pressure over the bed. X-ray computed tomography (XCT) provided detailed observations of the bed structure. Detailed 2D particle size data was obtained using automated microscopy and was analysed using an in-house developed tool. RESULTS: Crystal breakage is observed when the applied pressure exceeds a critical pressure: 0.5-1 bar for ibuprofen, 1-2 bar for ß-L glutamic acid (LGA) and 2-2.5 bar for para amino benzoic acid (PABA). X-ray computed tomography showed significant changes in bed density under the applied pressure. Size analysis and microscope observations showed two modes of breakage: (i) snapping of long crystals and (ii) shattering of crystals. CONCLUSION: LGA and PABA have a similar breakage strength (50 MPa), ibuprofen is significantly weaker (9 MPa). Available breakage strength data may be correlated to the volumetric Gibbs free energy. Data from 12 and 35 mm bed diameters compares well to literature data in a 80 mm filter; the smaller, easy to operate percolation unit is a versatile tool to assess crystal breakage in filtration operations.

Methylation of guanine in vivo by the organophosphorus insecticide methamidophos.

The methylating capability of methamidophos, assayed by the formation of [7-14C]methylguanine in mouse liver, was investigated using a 14C-insecticide labelled at the O--CH3 group. Following i.p. administration of the toxicant, [7-14C]methylguanine could be isolated from liver nucleic acids of treated mice. The amount of 14C-label reached its maximum 6 h following administration of the insecticide. At maximum 14C-labelling, the amount of 7-methylguanine calculated as fraction of applied dose, was 20-22 X 10(-4) and 98-104 X -4, for DNA and RNA, respectively. The results obtained indicate also, that an appreciable amount of 14C-activity is incorporate via the C-1 pool.