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Biological and Pharmaceutical Bulletin 1993-Jul

Pharmacological and pharmaceutical properties of freeze-dried formulations of egg albumin, indomethacin, olive oil, or fatty acids.

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Y Tsuji
H Kakegawa
H Miyataka
H Matsumoto
T Satoh

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Formulations consisting of egg albumin, indomethacin (IND), and olive oil or fatty acids, were prepared by vigorous stirring using a high-speed homogenizer and subsequent freeze-drying. To confirm the anti-inflammatory properties and ulcerogenic effects of the formulations, we examined the action of the formulations on carrageenan-induced edema in rats as well as their ulcerogenic actions in the same species. Compared with IND alone, albumin-IND-olive oil (9:1:4.3), albumin-IND-linolenic acid (9:1:4.3), albumin-IND-linolic acid (9:1:4.3), albumin-IND-oleic acid (9:1:4.3), albumin-IND-stearic acid (9:1:4.3), and albumin-IND-tristearin (9:1:4.3) formulations all exhibited a more potent inhibitory effect on carrageenan-induced edema. In addition, the inhibitory effects on edema formation of an albumin-IND (9:1) complex was as strong as that of IND alone. These results suggested that the bioavailability of IND was increased by olive oil, fatty acid, and tristearin as absorbefacient agents. The increase in the bioavailability was evident from the fact that the mean plasma levels, maximum plasma levels (Cmax), and area under plasma concentration-time curve (AUC) values after oral administration of the albumin-IND-olive oil (9:1:4.3) formulation was significantly greater than that after administration of the drug alone. With respect to their ulcerogenic properties, the formulations were significantly less active than IND alone, suggesting that a reduction in the ulcerogenic activity of IND was by produced complexation with egg albumin.

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