UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Effect of crystal anisotropy and crystal defects on dissolution Burt, Helen Mary

Abstract

There are a number of interesting and as yet unresolved problems concerning the dissolution rates and solubilities of various drugs. It seems clear that the inherent properties of crystals (i.e. surface and bulk structure and properties) and their relationship to solubility and dissolution rate need to be more clearly understood before explanations for these observations can be offered. The approach taken in this study to the problem of dissolution is to consider the method of preparation and its effect on crystal structure. This study attempts to show that, in addition to properties of the solid state such as polymorphism, solvation and degree of crystallinity, the dissolution kinetics may be affected by: a) the anisotropic nature of crystalline solids and hence crystal habit b) the type and number of crystal defects incorporated into a crystal during growth. Inorganic salts such as nickel sulfate hexahydrate (NiSO₄ α 6H₂O) and potassium perchlorate (KCIO₄) provided suitable model, crystalline materials as they grew as large, well-formed crystals with distinct habits. KCIO₄ crystals could be easily cleaved and etched and grew with relatively low dislocation densities. The dissolution anisotropy of NiSO₄ a 6H₂O crystals was studied using a single crystal dissolution method by measuring the movement of the (111) and (112) crystal faces with time in a flowing solvent using a travelling microscope. The observed apparent rate constant, Kobs for the (112) face was greater than for the (111) face at all flow rates but anisotropy was less pronounced at the lower flow rates, The apparent rate constants for the transport and surface controlled reactions, Kt and Kr were of the same order of magnitude suggesting that the overall dissolution reaction was under mixed control at the lower flow rates. Activation energies were slightly higher than the normal range for transport processes. Kr (112) > Kr (111) indicating that anisotropy was probably due to differences in the rate of the surface reaction. At high flow rates there was a change to a predominantly surface controlled reaction. It is likely that dissolution anisotropy is due to the differences in activation energy for the two faces. The effect of habit modification on the dissolution rate of NiSO₄ a 6H₂0 in 60% v/v ethanol was studied using a rotating basket method. Bipyramidal crystals were grown in a fluidized-bed crystallizer and platy crystals were recrystallized from supersaturated solutions of nickel sulfate containing small amounts of gelatin. Acicular crystals were prepared by the topotactic dehydration of acicular crystals of NiSO₄.7H₂O. DSC thermograms of platy and acicular habits were similar but differed from the bipyramidal habit probably due to differences in vapor pressures exerted by the habits. The observed dissolution rate constant, K'obs. for the bipyramidal and acicular crystals was similar and greater than the platy habit at both low and high rotation rates, the difference being less pronounced at the lower rotation speed. At the high rotation speed dissolution was under mixed transport-surface control . The difference in K' obs must be due to different values of the overall surface energy of the crystals. KCIO₄ crystals were grown in silica gels and the crystals from three growth levels (and hence grown at different rates) were cleaved, etched and the dislocation etch pits counted using a differential interference contrast microscope. Crystals grown at the fastest rate had the highest mean dislocation densities and the highest K'obs values as determined using the rotating basket method. Conversely, crystals grown at the lowest rate had a low mean dislocation density and low K'obs values. The differences in K'obs were not due to impurities but to differences in the energy content of crystals resulting from the incorporation of differing numbers of dislocations into the crystals.

Item Media

Item Citations and Data

License

For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.

Usage Statistics