PART I: ENTRAPMENT OF SODIUM STIBOGLUCONATE IN LIPOSOMES. PART II: EFFECT OF SOLVENT DENSITY ON SOLID-LIQUID AND LIQUID-LIQUID MASS TRANSFER
Abstract
Part I. Sodium stibogluconate entrapped in liposomes composed of egg lecithin, cholesterol, and dicetyl phosphate in a molar ratio of 7:2:1 respectively, was studied with regard to efficiency of entrapment, effect of swelling time and/or temperature on entrapment efficiency, and the permeability of entrapped sodium stibogluconate at 4(DEGREES), 25(DEGREES), 35(DEGREES), and 45(DEGREES)C. All of the temperatures were above the transition temperature of the phospholipid component, egg lecithin. The entrapment efficiency ranged from a low of 2.03% at 45(DEGREES)C to a high of 2.88% at 4(DEGREES)C. The swelling studies indicated that there was no temperature dependence on the amount of sodium stibogluconate entrapped during the swelling period. Therefore, it would be difficult to select a standard swelling time for all liposome systems. The permeability study illustrated a slight temperature dependence with a faster release of entrapped sodium stibogluconate from a span of 4(DEGREES)C to 35(DEGREES)C. Also a biphasic release, which is characteristic of liposome systems, was observed at 4(DEGREES)C and 25(DEGREES)C, while this was not observed at 35(DEGREES)C and 45(DEGREES)C. Part II. The effect of solvent density on solid-liquid and liquid-liquid mass transfer was studied in order to determine the mechanism of dissolution. The solid-liquid mass transfer data suggested that the mechanism of dissolution was controlled by the solute transport rate from the solid-liquid interface as opposed to an interfacially controlled process. However, when the solid-liquid mass transfer data was compared to the liquid-liquid mass transfer data, the opposite conclusion was reached; that is, dissolution is an interfacially controlled process. The concentration at the solid-liquid interface was determined to be 3.62 x 10('-4) g/ml which was very close to the previously determined value of 4.25 x 10('-4) g/ml. The use of sodium chloride solutions as the dissolution solvent appeared to decrease the effective interfacial concentration to the point where diffusion was responsible for mass transfer. Finally, it was recognized that the prediction of the dissolution mechanism from dissolution rate data alone was questionable.
Degree
Ph.D.
Subject Area
Pharmaceuticals
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