| Description |
The potential of several commercially available polymeric materials for use in controlled release drug delivery devices has been investigated. Progesterone has been used as a model hydrophobic drug. The rates of progesterone permeation through Silastic, Bicmer, Pel!ethane, pHEMA, Avcothane, and Cuprophan have been determined. The permeabilities have been obtained on non-plasma soaked membranes and on membranes soaked in plasma for varying periods of time. The purpose of the plasma soaks was to determine the effects of lipid absorption and degradative processes within the membrane on the permeability of progesterone. This study has identified several polymers which show potential for use in controlled release drug delivery devices in vivo. The plasma treatment studies have shown that several polymers may not be acceptable. Attempts have been made to interpret the plasma soak studies in terms of the mechanisms of drug permeation through the membranes. This was done to reach conclusions which may apply in general to the effects of plasma on the rates of permeation of hydrophobic drugs through polymer membranes. Permeation, diffusion, and partition coefficients of progesterone in hydrogels made from HEMA cross-linked with varying amounts of EGDMA and TEGDMA were determined. In addition, copolymers of HEMA with MEEMA and MEMA were investigated. The results of these studies were interpreted in terms of the mechanisms of permeation. Progesterone appears to permeate these gels primarily through loose pores in the gel network except at high concentrations of EGDMA, where dissolution and diffusion of the progesterone in the polymer network is the dominant mechanism. Progesterone permeation rates through hydrogels can be varied over a wide range by altering the cross-linker concentration or through the use of copolymers; the latter are chosen to alter the equilibrium hydration of the hydrogel. Hydrogels may be synthesized under a variety of conditions which differ with respect to temperature, initiator, and solvent. A study of the effect of the solvents water, ethanol, and tert-butanol at various concentrations, used during polymerization on the permeability of progesterone through pHEMA films was conducted. The results demonstrate that progesterone permeation through the films is independent of the polymerization solvent. The importance of the equilibrium hydration of the gels is emphasized. Permeation, diffusion, and partition coefficients of progesterone, testosterone, 19-nortestosterone, norethindrcne, 17«<-hydroxyprogesterone, estradiol, and Cortisol were determined in HEMA film with (film II) and without (film 1} 5.25 mole percent EGDMA. A model for solute permeation was proposed which is based on the separation of a domain (B) composed of bulk-like" water from the rest of the gel, domain (A). An analysis of the steroid permeation data in accordance with the model indicated permeation in film II occurred via the "solution-diffusion" mechanism. Permeation in film I occurred predominately by the "pore" mechanism with approximately 20 percent by the "solution-diffusion" mechanism. Solute functional group contributions to permeation in film II were ascribed to either steric or hydrogen bonding effects. |
