Date of Award
1988
Document Type
Thesis
Degree Name
Master of Science (M.S.)
Department
Graduate School
First Advisor
Ravindra C. Vasavada
First Committee Member
Herschel Frye
Second Committee Member
Donald Y. Barker
Abstract
The effect of an endoqenous surfactant, palmitylcarnitine chloride (PCC), on the solubility of etoposide was investigated. Preliminary studies were conducted to establish optimum experimental conditions for subsequent equilibrium solubility determinations. Infrared spectroscopy and thin layer chromatography techniques were used to establish the purity and identity of PCC. PCC was found to undergo rapid hydrolysis in aqueous solutions at 37.0° ± 0.5° C and the degradation was independent of concentration. The effect of pH on the stability of PCC was investigated. These studies revealed that PCC was most stable in the range pH 3.0 - 4.0. Etoposide was found to be stable in pH 4.0 buffer for at least seven days (< 3.9% degradation) and in the presence of PCC (7. 2 x 10-1 mM/L) for at least three days· (< 5.2% degradation) and therefore, pH 4.0 acid phthalate buffer was chosen as the dissolution medium for the solubility studies.
The critical micellar concentration (CMC) of PCC was determined in pH 4. 0 buffer at 37.0° + 0.5° C by the spectral Change Method using eosin Y. The CMC was found to be 7. 66 x 10-4 mM/L.
The equilibrium solubility of etoposide in pH 4.0 buffer and at three concentration levels of PCC was determined at 37.0° ± 0.5° C. The concentrations of PCC solutions studied were 8.42 x 10-1 mM/L (PCC 1), 0.482 x 10-1 mM/L (PCC II), and 7.00 X 10-3 mM/L (PCC III) respectively. In the presence of PCC it was found that etoposide solution achieved equilibrium within five minutes as against two hours required in pH 4.0 buffer alone. Dunnett's t test indicated no significant increase in etoposide solubility in PCC I and PCC III. At the highest concentration, that is in PCC II, the solubility of etoposide was found to be 7% higher than in pH 4.0 buffer alone.
Pages
87
Recommended Citation
Kashyap, Lola. (1988). Studies on the effect of palmitylcarnitine chloride on the solubility of etoposide. University of the Pacific, Thesis. https://scholarlycommons.pacific.edu/uop_etds/2169
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