PubMed · 5438325
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J W Wasley, W T Scott, A S Holt. 1970. Chlorophyllides c.. https://pubmed.ncbi.nlm.nih.gov/5438325/
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Solid dispersions of PEG6000 and loperamide-a poorly water-soluble agent-were prepared by spray drying. Their physicochemical properties were evaluated immediately after preparation. The dissolution was higher than that of pure crystalline loperamide. DSC- and XRD-measurements revealed that in the dispersions, loperamide is partially present in the crystalline state. A eutectic state diagram was obtained. The samples containing 20% loperamide were stored under different conditions (40 degrees C and 0% RH, 25 degrees C and 52% RH, 4 degrees C and 0% RH) to investigate their stability as a function of time. The dissolution properties deteriorate upon storage at high temperature (40 degrees C and 0% RH) and in conditions of higher relative humidity (25 degrees C and 52% RH). The DSC-curves clearly indicate an increase in the amount of crystalline compound under these conditions. From these observations it could be concluded that loperamide, which is partially crystalline and partially amorphous in the freshly prepared samples, continues to crystallize under these conditions, resulting in progressively poorer dissolution properties.
The incorporation of a drug in a carrier by melt embedding may either result in a solid solution or in a solid suspension of the active ingredient within the carrier material. As the dispersivity of the drug is of outstanding importance for its dissolution characteristics, parameters which are supposed to influence crystallinity and dispersivity, e.g. cooling rate during preparation and storage conditions like temperature and relative humidity are investigated. It is found that the absence of crystalline drug material in solid dispersions containing nimodipine and polyethylene glycol 2000 is the prerequisite for a high dissolution rate and a remarkable supersaturation in the dissolution medium. Shock freezing during the preparation process, low storage temperatures and low relative humidities are identified to prevent recrystallisation. Furthermore, emphasis is put on the physico-chemical characterisation of solid dispersions. It is shown that the determination of crystallinity and dispersivity of the drug in solid dispersions can only be successful by combining different investigation methods like differential scanning calorimetry, hot stage microscopy, X-ray diffraction as well as macroscopic observation.
Macro-scale simulations often play an important role in the assessment and remediation of contamination by dense non-aqueous phase liquids (DNAPLs) in the subsurface. Effective parameters for the macro scale are required for these simulations in order to avoid a detailed discretisation of the geological structures. Starting from the observed influence of heterogeneities on multiphase flow processes at the macro scale, we present an upscaling procedure from the local to the macro scale for the derivation of constitutive relationships for multiphase flow processes. The approach is based on the assumption of an equilibrium of (capillary) forces, which allows the application of a percolation model. This results in saturation distributions for different capillary pressures. Averaging these distributions gives rise to a macroscopic capillary pressure-saturation relationship. For the saturation distribution, relative permeabilities and effective conductivities are computed depending on the structure and the flow direction. These are averaged with the help of the renormalisation method. The evolving relative permeability-saturation relationship for the macro scale shows a saturation-dependent anisotropy and pronounced residual saturations of the nonwetting phase (which were not assumed for the local scale). The anisotropy reflects the underlying structure of the considered system that needs not to be known in detail.