Date of Award

Fall 1996

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemical Engineering - (Ph.D.)

Department

Chemical Engineering, Chemistry and Environmental Science

First Advisor

Kamalesh K. Sirkar

Second Advisor

Basil Baltzis

Third Advisor

David Kafkewitz

Fourth Advisor

David S. Kristol

Fifth Advisor

Norman W. Loney

Abstract

A novel controlled release device based on aqueous-organic partitioning is described. The device comprises a reservoir, bounded by a microporous or porous membrane in the form of a hollow fiber or flat film. The reservoir liquid phase and the pore liquid phase are immiscible. The agent partitions between the phases at the aqueous-organic interface of the reservoir and the pore mouth, and then diffuses through the membrane pore liquid into a surrounding aqueous solution. The partition coefficient significantly influences the rate of release of the agent by reducing the driving force for diffusion across the fluid-filled membrane pore. The performance of the system is evaluated using model agents benzoic acid, caffeine, nicotine and phenylalanine-glycine. Two aqueous-organic configurations were investigated: an agent in an organic reservoir solution with water-filled pores, and an agent in an aqueous reservoir with organic filled pores. Specifically, the model systems included benzoic acid in three reservoir solvents (octanol, decanol, and mineral oil) partitioning into waterfilled pores, an aqueous reservoir of nicotine partitioning into either mineral oil- or octanol-filled pores, and caffeine or phenylalanine-glycine partitioning into octanol-filled pores. The peptide phenylalanine-glycine was used to investigate pH-based controlled release from this type of device. Studies using benzoic acid demonstrate the effectiveness of a thin, nonporous coating on the release rate. When a fast-dissolving dispersion of the agent is present in the reservoir, the period of zero order release is extended; when the dispersion dissolves slowly, the release rate is decreased and the period of zero order release is extended. Simultaneous release of two agents (benzoic acid and nicotine, nicotine and caffeine) from a single reservoir and from two separate reservoirs was achieved. Models are presented for many of these systems. Solutions have been developed to describe the observed release, and dimensional analysis was used to identify important parameters which govern the release rate of the agent from the device. Finally, a new technique is presented for achieving controlled release of liposomes from a membrane-type diffusion based controlled release system.

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