Solubilization and dissolution properties of a leukotriene-D4 antagonist in micellar solutions.
7-[3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propoxy]-3,4-dihydro-8- propyl-2H-1-benzopyran-2-propionic acid (1) is a leukotriene-D4 antagonist that is quite insoluble in aqueous media. Increased solubilization of 1 was achieved in micellar solutions of polysorbate 80, sodium glycocholate, sodium taurocholate, lysolecithin, and sodium taurocholate plus monoolein. The intrinsic dissolution rate of 1 was measured in the presence and absence of polysorbate 80 at pH 7.0, 8.0, and 10.0. In all the micellar solutions tested, the solubility of 1 was significantly increased. The intrinsic dissolution rate of this compound was also enhanced in micellar solutions of polysorbate 80 and with increasing values of pH. However, the magnitudes of the enhancement of the intrinsic dissolution rate were much less than expected from the enhancement of aqueous solubility.
Kararli
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G.D. Searle Research and Development, Advanced Drug Delivery Group, Skokie, IL 60077.
Gupta
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D001578:Benzopyrans / Q000737:chemistry*; D001647:Bile Acids and Salts / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000737:chemistry; D008823:Micelles; D011136:Polysorbates / Q000737:chemistry; D013189:SRS-A / Q000037:antagonists & inhibitors*; D012995:Solubility; D012996:Solutions
D001578:Benzopyrans; D001647:Bile Acids and Salts; D005989:Glycerides; D008244:Lysophosphatidylcholines; D008823:Micelles; D011136:Polysorbates; D013189:SRS-A; D012996:Solutions; C076962:7-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy)-3,4-dihydro-8-propyl-2H-1-benzopyran-2-propionic acid; C005953:monoolein