Study of partition of nitrazepam in bile salt micelles and the role of lecithin

The effect of trihydroxy (sodium cholate and sodium glycocholate) and dihyd roxy (sodium deoxycholate and sodium glycodeoxycholate) bile salt micelles on the spectrophotometric properties and on the solubility of nitrazepam in aqueous solution, at 25.0 degreesC and at ionic strength 0.1 M in sodium c hloride, has bren assessed. From the results obtained it was possible to ca lculate the partition coefficients (K-p) of nitrazepam between aqueous and micellar phases. The partition coefficients of nitrazepam have also been de termined in mixed micelles of cholate or deoxycholate with lecithin (egg yo lk phosphatidylcholine), which were used as a model of the gastrointestinal tract. Drug partition was found to depend on the bile acid (number of hydr oxyl groups and conjugation with glycine), and our data indicate further th at addition of lecithin to bile salt micelles decreases the values of the p artition coefficients in the mixed micelles at physiological pH. (C) 2001 E lsevier Science B.V. All rights reserved.