Browsing by Subject "salts"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Maximum Application Rates for Land Treatment of Septage
    (Water Resources Research Center, University of Minnesota, 1983-05) Anderson, James L.; Clanton, C.J.; Hansel, M.J.; Machmeier, R.E.
    During 1980, septage was applied in rates of 1120 and 1500 kg of nitrogen per hectare to three different soil textures in an attempt to determine maximum loading rates. These rates resulted in increased concentrations of nitrates in the soil water for a Hubbard loamy Sanci, Waukegan silt loam and Lester clay loam, indicating that the application rates exceeded the maximum rate that the soils could treat. The first year's results indicate that soil type, application rates and soil depth resulted in no significant difference in total Kjeldahl nitrogen, ammonia, fecal streptococcus and fecal coliforms in the soil water samples. Nitrate concentrations, however, were significantly different between the soils, application rates and soil depths. For the Hubbard loamy sand, rainfall had a larger effect on nitrate concentrations and movement within the soil profile than for the Waukegan silt loam or Lester clay 1oam. 0n the Waukegan silt loam and Lester clay loam there was relatively little change in the nitrate concentration in the soil profile during the period when septage was applied twice a week. After the design loading had been applied to the soil and no further applications made, a sharp increase in nitrate concentrations was observed in the soil profile. This probably resulted from changing the anaerobic surface layer to an aerobic condition resulting in nitrification and subsequent movement of nitrates through the profile following a rainfall event. With no additional septage application, the second year's data indicate a significant difference in nitrate-N between soils, application rates, and depths. Generally, the nitrate concentrations in the Hubbard loamy sand and Waukegan silt loam were less than the first year, but the concentrations in the Lester clay loam were higher than the first year. This indicates that nitrification and nitrate movement in the Lester clay loam are slower than the other two soils. Application resulted in a significant increase in the concentration of soil water calcium, magnesium, sodium and potassium during the first year of the study. However, there was no increase in the phosphorus content of the soil water.
  • Thumbnail Image
    Item
    UNDERSTANDING THE STABILITY OF SALTS AND COCRYSTALS IN A DRUG PRODUCT ENVIRONMENT
    (2021-06) Kaur, Navpreet
    Transition of a drug substance to drug product necessitates the use of excipients and often includes several unit operations.1 A risk associated with processing pharmaceutical solids is their propensity to undergo solid form transformations such as polymorphism and amorphization. Changes in the physical form during drug product manufacture or storage can have an influence on their chemical stability and product performance. The central goal of this thesis work is to mechanistically understand the influence of processing and formulation composition on the stability of pharmaceutical salts and cocrystals.Processing induced lattice disorder was investigated for caffeine-oxalic acid cocrystals. The unmilled cocrystals were stable in presence of excipient and water. However, very short milling times induced sufficient lattice disorder to induce cocrystal dissociation. Quantification of disorder was performed using X-ray diffractometry (XRD). The lattice disorder was proposed to be predominant on the particle surface experiencing shear and hence served to explain the disproportionate influence that low levels of disorder had on the stability of the cocrystals. Cocrystal dissociation was observed to be a water mediated reaction and was influenced by the pH of the microenvironment. Very low levels of lattice disorder, which cannot be characterized using bulk characterization tools such as XRD and thermal analysis, can induce chemical instability and lead to product failure. Disorder induced during processing was also imaging using atomic force microscopy. The second part of the thesis focused on understanding the challenges associated with the formulation development of levothyroxine sodium pentahydrate (LSP). The influence of pharmaceutical processing on the hydration state of LSP was investigated using single crystal and synchrotron X-ray diffractometry, and a novel crystal form of the drug was reported when it undergoes partial dehydration to form levothyroxine sodium monohydrate (LSM). LSM has a higher chemical reactivity than the pentahydrate form. The influence of excipients on the physical and chemical stability of LSP was investigated using synchrotron XRD and high performance liquid chromatography (HPLC). Hygroscopic and acidic excipients can induce dehydration and salt disproportionation of LSP, respectively. Microenvironment pH and excipient hygroscopicity were critical determinants of LSP stability.