Date of Award


Degree Type


Degree Name

Doctor of Philosophy in Pharmaceutical Sciences


Interdepartmental Program

First Advisor

Christopher T. Rhodes


Strict anti-pollution laws have drastically changed how pharmaceutical manufacturers operate. Increased environmental awareness has forced changes in the way that sustained release pharmaceuticals are manufactured. Coatings which were once applied from organic solutions have been reformulated into water based polymeric dispersions that, although effective, cannot equal the performance of their predecessors. Research has led to updated coatings composed of three time tested polymers; cellulose acetate, ethylcellulose and methacrylic acid copolymer. Additionally, new coatings have been manufactured from custom polymers which provide excellent sustained release. Unfortunately, their development has not progressed beyond the laboratory since regulatory bodies worldwide are reluctant to approve new polymers for use in vivo. Clearly there exists a need for new coating materials that are "environmentally friendly, " approvable for in vivo use, and effective. An attempt was made to identify materials which, in addition to imparting sustained release, could be used safely, without organic solvents. The crosslinking of a water soluble polymer was decided to be the most feasible means of achieving that goal. Hence hydroxyethylcellulose (HEC), a water soluble, GRAS (generally recognized as safe) polymer was identified and evaluated under various conditions. The ability to insolubilize films of HEC was demonstrated when films containing riboflavin-5'-phosphate were exposed to visible or ultraviolet light. The drug release controlling potential of those films was demonstrated by their application to tablets containing model drugs, and their subsequent insolubilization via visible light exposure. Release rates of tablets with crosslinked coatings were determined in vitro and found to be nearly zero order and well controlled, in both water and 0.1 N HCI. The ( (shortcomings of this technique lie in the difficulties in quantitatively assaying the crosslinked polymer. Since the crosslinked polymer is largely water and organo-insoluble, attempts were made to differentiate between crosslinked and uncrosslinked polymer. To date none of the techniques evaluated provides a means to differentiate between the HEC's. While analysis of the crosslinked polymer has proven difficult, a system capable of providing for the sustained release, composed entirely of GRAS materials and not requiring organic solvents, has been realized.



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