Date of Award

1982

Degree Type

Dissertation

Degree Name

Doctor of Pharmacy (PharmD)

First Advisor

Christopher T. Rhodes

Abstract

Accurate, precise, sensitive and reproducible experimental protocols using high pressure liquid chromatographic assay techniques (HPLC) have of solutes across liquid membranes. A simple model, previously developed by Rhodes and co-workers, used to describe the kinetics of solute transport across liquid membranes was evaluated and some formulation aspects of emulsions for use as liquid membranes were studied. The removal of solutes from an external aqueous phase by a liquid membrane was found to be influenced by a number of factors including initial solute concentration, pH of the external aqueous phase, and temperature of the system. As the initial concentration of solute increased, the apparent transport rate constants decreased. This was observed for both single and multicomponent systems. Increasing the pH of the external aqueous phase resulted in reduced transport rate constants for salicylic acid. This is in agreement with the pH-partition theory. An attempt was made to predict the uptake of salicylic acid as a function of pH using a Computer Simulation Modeling Program. Lack of quantitative agreement between experimental and predicted data is attributed to the complexity of the systems and insufficiency of the model. Salicylic acid uptake increased as a function of temperature in apparent agreement with the Arrhenius equation. Similarly, the uptake of phenobarbital by a liquid membrane system appears to obey the Arrhenius relationship until a “critical” temperature or temperature range was reached (about 43°C). Above the critical temperature, the transport rates of phenobarbital decreased as temperature was increased. Increasing the viscosity of the liquid membrane at the critical temperature did not help to improve transport at this temperature range. Alterations in the physical properties of liquid membranes resulted in changes in the rate of solute uptake. Increasing viscosity and oil/ water ratio both resulted in reduced transport rate constants for the uptake of solutes. These effects can be readily interpreted using classical diffusion theory. Liquid membranes which were frozen and thawed were satisfactorily used for drug removal indicating the surprising robustness of these systems. Studies reported in this thesis indicate that previous use of liquid membranes for solute transport does not materially affect their further use as sinks. These systems also demonstrated the ability to remove simultaneously two solutes from a multicomponent system at rates which were of the same magnitude as that measured in one solute systems. Method of manufacture and appropriate surfactant blends were determined to be key factors in the development of emulsions for use as liquid membranes formulated using only Generally Regarded As Safe components (GRAS). Liquid membrane systems prepared by the investigator using only GRAS components would need substantial further development work before commercialization could be effected; however, they do appear to merit additional studies for a number of possible pharmaceutical uses.

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