TY - JOUR

T1 - Biorelevant dissolution media

T2 - aggregation of amphiphiles and solubility of estradiol

AU - Ilardia-Arana, David

AU - Kristensen, Henning G

AU - Müllertz, Anette

N1 - Keywords: Animals; Bile Acids and Salts; Biological Availability; Buffers; Chemistry, Physical; Chromatography, High Pressure Liquid; Estradiol; Glycerides; Micelles; Molecular Weight; Phosphatidylcholines; Solubility; Structure-Activity Relationship; Technology, Pharmaceutical; Water

PY - 2006

Y1 - 2006

N2 - Biorelevant dissolution media containing bile salt and lecithin at concentrations appropriate for fed and fasted state are useful when testing oral solid formulations of poorly water-soluble drugs. Dilution of amphiphile solutions affects the aggregation state of the amphiphiles because bile salt is partitioned between the aqueous phase and the aggregates. The aim of the investigation was to study the effect of dilution on the size distribution of aggregates and its effect on the solubilization capacity. Clear buffered solutions of four intestinal amphiphiles (sodium glycocholate, lecithin, monoolein, and oleic acid) and a combination of these were prepared at high bile salt concentration. Micelles in the glycocholate solutions decreased in size when diluted. The addition of insoluble amphiphiles led to bigger micelles with no clear correlation between size of the micelles and amphiphile concentration. Dilution of the two- and four component media caused enlargement of the mixed micelles and formation of vesicles. The solubility of estradiol in the buffer solution was increased with addition of the amphiphiles. A good correlation (R(2) = 0.987) was found between estradiol solubility and mass concentration of the amphiphiles. The results demonstrate that, in the case of estradiol, the concentration of amphiphiles rather than the aggregation state determines the solubilization capacity of the medium.

AB - Biorelevant dissolution media containing bile salt and lecithin at concentrations appropriate for fed and fasted state are useful when testing oral solid formulations of poorly water-soluble drugs. Dilution of amphiphile solutions affects the aggregation state of the amphiphiles because bile salt is partitioned between the aqueous phase and the aggregates. The aim of the investigation was to study the effect of dilution on the size distribution of aggregates and its effect on the solubilization capacity. Clear buffered solutions of four intestinal amphiphiles (sodium glycocholate, lecithin, monoolein, and oleic acid) and a combination of these were prepared at high bile salt concentration. Micelles in the glycocholate solutions decreased in size when diluted. The addition of insoluble amphiphiles led to bigger micelles with no clear correlation between size of the micelles and amphiphile concentration. Dilution of the two- and four component media caused enlargement of the mixed micelles and formation of vesicles. The solubility of estradiol in the buffer solution was increased with addition of the amphiphiles. A good correlation (R(2) = 0.987) was found between estradiol solubility and mass concentration of the amphiphiles. The results demonstrate that, in the case of estradiol, the concentration of amphiphiles rather than the aggregation state determines the solubilization capacity of the medium.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1002/jps.20494

DO - 10.1002/jps.20494

M3 - Journal article

C2 - 16374874

VL - 95

SP - 248

EP - 255

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 2

ER -