Solubility and Dissolution of Etoposide from Solid Dispersions of PEG 8000

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Abstract
The Solubility and dissolution of etoposide from solid dispersion of PEG 8000, prepared by the fusion method, were investigated. Stability studies revealed that the etoposide was stable in water for three days at 37 ± 0.5°C alone and as a physical mixture with PEG 8000. However, nearly 5% decomposition was oberved in aqueous solutions made from solid dispersions. TLC, IR and HPLC studies showed both the drug and carrier were stable during the fusion process. 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, and found to be significantly higher than that of etoposide alone or from its physical mixtures with PEG 8000. 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 only 1:40 etoposide: PEG 8000 physical mixture demonstrated a significant increase in etoposide solubility (16.1%). Dissolution studies, on the solid dispersions in water at 37 ± 0.5°C, revealed a marked increase in the dissolution rate of etoposide from 1:20, 1:30 and 1:40 solid dispersions with 100% drug dissolving within 1 minute; dissolution time for 1:5 and 1:10 dispersions, and all physical mixtures was 3 minutes while etoposide alone required 30 minutes for complete drug dissolution. The melting behavior of the etoposide-PEG 8000 mixtures and subsequent thermal analysis of the melts suggested that the increase of solubility of etoposide was mostly due to the formation of a solid solution of etoposide in PEG 8000.