The Role of Phase Inversion in the Drug Release Kinetics of Injectable Polymer Solutions
DesNoyer, Jessica Renee
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/82343
Description
Title
The Role of Phase Inversion in the Drug Release Kinetics of Injectable Polymer Solutions
Author(s)
DesNoyer, Jessica Renee
Issue Date
2002
Doctoral Committee Chair(s)
McHugh, Anthony J.
Department of Study
Chemical Engineering
Discipline
Chemical Engineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biophysics, Medical
Language
eng
Abstract
Phase inversion is a process in which a concentrated polymer solution is converted into a solid gel network with desirable end-use properties. In this thesis, studies of the role nonsolvent induced phase inversion plays in the protein release kinetics of injectable drug delivery devices are presented. In situ optical techniques coupled with scanning electron microscopy (SEM) and high performance liquid chromatography (HPLC) were used to examine the relationship between the phase separation dynamics, morphology development, and drug release kinetics of in situ precipitating controlled release devices. In the first study, the effect of solvent quality and bath-side composition was examined. Thermodynamic phase diagrams for three model systems suggest precipitation behavior varies depending on the relative strength and aqueous miscibility of the solvent. Drug release from depots with a high solvent-nonsolvent (S-NS) affinity is controlled predominantly by the phase inversion dynamics, while depots with a low S-NS affinity undergo much slower phase inversion rates and release protein more uniformly. Furthermore, bath side additives can evoke a significant increase in the protein mass transfer rate from low S-NS affinity depots. In the second study, the effect of polymer crystallinity was examined. Varying the degree of crystallizability of polymer solutions led to two classes of depots. Depots with high degrees of crystallinity have porous morphologies indicative of solid-liquid de-mixing and delayed burst release profiles. Depots with low degrees of crystallinity have dense morphologies formed by liquid-liquid de-mixing and slow, uniform release rates. In the third study, the effect of incorporating preferentially segregating additives into the depot formulation was examined. During phase separation, the additive preferentially segregates to the hydrophilic polymer-lean phase and, thereby, influences the release properties. Increasing the additive concentration beyond a critical point induces a transformation from a burst-type release profile to an extended-release profile. In the last study, the effect of protein composition was examined. Lyophilizing protein with watersoluble excipients leads to enhanced release rates. Additionally, physiochemical variations in excipient molecules result in varying release characteristics that are dependent on the induced osmotic pressure gradients. These results suggest realistic ways of controlling the performance of injectable controlled release devices.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
