Title

Investigation into the use of glassy gelatin beads as a swelling-controlled drug delivery system

Date of Completion

January 1987

Keywords

Health Sciences, Pharmacy

Degree

Ph.D.

Abstract

The fundamental principle of a swelling-controlled drug delivery system is nonFickian transport of solvent into a glassy polymer matrix. The velocity of the advancing solvent front can determine the drug release rate.^ Initial stages of the development of gelatin as a swelling-controlled drug delivery system required the identification and characterization of influential parameters associated with the swelling behavior of the glassy gelatin matrix. For example, swelling studies using different solvents demonstrated a size selectivity, in which a known solvent for gelatin could not penetrate the glassy matrix due to its large molecular size. Also, by the estimation of effective crosslink density, the distinction was made between chemical and physical crosslinks.^ Two moving boundaries are associated with this swelling system, the penetrating water front and outer swelling gelatin front. Both boundaries were measured directly with an optical microscope as a function of time. Interestingly, the water front profile exhibited three distinct regions: an initial square root of time region (Fickian), a steady state velocity region (apparent Case II transport), and a final region where the front accelerated near the bead's center (apparent Supercase II transport).^ Subsequent studies focused primarily on variables that affect the water front steady state velocity which include: initial size of a dry bead, crosslink density, solvent-induced stress on the glass-gel interface, and most importantly, the efficiency in molecular packing of the glassy matrix (swelling history). A correlating function was then proposed on the basis of dimensional analysis and experimental observations.^ Incorporation of the model drug, isoniazid (INH), into gelatin beads altered the structure and hence swelling behavior of the glassy matrix. Plasticization of gelatin chains by INH was postulated as the primary factor for inducing the increase in water front velocity for beads with greater drug content. Fractional release rates were studied as a function of crosslink density, drug load, and device size, in addition to moving boundary analysis. These combined results provide evidence that INH release rates were dependent on the water front velocity. ^