The benefits of controlled release drug delivery are important to the
pharmaceutical industry. With a controlled release device, local administration of a drug
is possible and release profiles can be created that remain within therapeutic limits for
prolonged periods. Made from biodegradable and bioerodable polymers, unwanted side
effects and the need of return trips for treatment diminish. However, a usable device
must be free of organic solvents normally used to dissolve large drug molecules. Many
of these solvents are toxic themselves. Therefore, steps must be taken to either remove
residual solvent from the final device or limit their use during synthesis.
Ideally, it is desirable to remove the organic solvents from the process entirely.
Supercritical carbon dioxide (scCO2) has been used as a replacement for these solvents.
Carbon dioxide is inexpensive, environmentally acceptable, and safe for use in human
consumables. However, many drug molecules have very low solubility in scCO2,
resulting in extended polymer impregnation times. An organic co-solvent can be used to
increase drug solubility, leading to a more efficient polymer impregnation. Using only a
small amount of organic co-solvent, a single phase stream is possible that results in
significantly increased solubility. This meets the original task of limiting organic
solvents in the process and increases efficiency over scCO2 alone.
This study uses supercritical carbon dioxide with ethanol as a co-solvent.
Ethanol increases the solubility of ò-estradiol in scCO2 for impregnation into the glassy
polymer polyvinylpyrrolidone (PVPP). Experimental conditions cover a range of temperatures from 40 ðC to 50 ðC and pressure up to 2500 psi. The effect of polymer
swelling time on the sorption process is also studied. A dual mode sorption model
describes the sorption of drug into the glassy polymer, and a plug flow and stirred tank
compartmental model predicts breakthrough profiles. The determined sorption
parameters allow analysis of polymer conformation and suggest optimum impregnation
conditions.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/4735 |
| Date | 25 April 2007 |
| Creators | Bush, Joshua R. |
| Contributors | Hall, Kenneth R |
| Publisher | Texas A&M University |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | 2086649 bytes, electronic, application/pdf, born digital |
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