Date of Award

1990

Document Type

Thesis - Pacific Access Restricted

Degree Name

Master of Science (M.S.)

Department

Graduate School

First Advisor

Ravindra Vasavada

First Committee Member

Madhukar Chaubal

Second Committee Member

Michael Mergener

Abstract

The solid glass dispersions of xylitol or PEG 8000 containing etoposide were prepared by the fusion method. The preliminary studies established that the etoposide was stable in water for three days at 37• ±. 0. s•c either from solid glass dispersion or physical mixture with xylitol or PEG 8000, with no significant change in pH. Thin layer chromatography and infra red spectroscopy of the samples suggested that the drug and the carrier (xylitol or PEG 8000) were stable and did not decompose during the fusion process. The solubility of etoposide from solid glass dispersion with etoposide:xylitol ratios of 1:5, 1:10, 1:20, 1:30 and 1:40, was studied at 37• ±. 0.5•c, and found to be significantly higher than that of etoposide alone in water. The 1:20 dispersion provided maximum enhancement (120.7%) of etoposide solubility. The aqueous solubility of etoposide from physical mixtures with etoposide:xylitol ratios of 1:5 to 1:40, under the same conditions, was only 22% higher than that of pure etoposide. The time for complete dissolution of etoposide in water at 371 .±. 0.5•c from solid glass dispersions (1:10, 1:20, 1:30 and 1:40) was 1 minute, compared with 30 and 15 minutes for pure etoposide and 1:20 physical mixture respectively. The aqueous solubility of etoposide from solid dispersions with etoposide:PEG 8000 ratios of 1:5, 1:10, 1:20, 1:30 and 1:40, was studied at 37• ±. 0. 5 • C. These dispersions increased the solubility of etoposide by 32.3%, 96.8%, 133.5%, 280.7% and 326.6% respectively compared to that of etoposide alone, whereas all physical mixtures were relatively ineffective except 1:40 physical mixture, which showed a 16.1% increase. A marked increase in the dissolution rate of etoposide was noted for solid dispersions with 1:20, 1:30 and 1:40 etoposide: PEG 8000 ratios with 100% drug dissolving within 1 minute compared to 3 minutes for all the physical mixtures. The analysis of thermograms obtained from the differential scanning calorimeter showed no evidence of any chemical interaction or eutectic formation between the drug and either carrier, xylitol or PEG 8000. The thermograms strongly suggested that etoposide dissolved in the molten PEG 8000 but not in the molten xylitol. It is suggested that the improvement in the solubility and dissolution of etoposide (a highly lipophilic compound) from xylitol dispersions was due to its enhanced hydrophilicity and wettability by fused Xyli tol. On the other hand, as also confirmed by phase diagram, the increase of solubility and dissolution of etoposide from PEG 8000 dispersions was due to a formation of solid solution of etoposide in PEG 8000.

Pages

82

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