TY - JOUR
T1 - Stabilizer choice for rapid dissolving high potency itraconazole particles formed by evaporative precipitation into aqueous solution
AU - Sinswat, Prapasri
AU - Gao, Xiaoxia
AU - Yacaman, Miguel J.
AU - Williams, Robert O.
AU - Johnston, Keith P.
N1 - Funding Information:
The authors gratefully acknowledge financial support from The Dow Chemical Company (Midland, MI). The authors would also like to thank Drs. Jason McConville for his helpful discussion and Xiaoxia Chen for her skilled assistance with the adsorption study.
PY - 2005/9/30
Y1 - 2005/9/30
N2 - The objective of this study was to investigate the influence of stabilizer type on the physicochemical properties, including dissolution, of ultra-high potency powders containing itraconazole (ITZ) formed by evaporative precipitation into aqueous solution (EPAS). ITZ was dissolved in dichloromethane, which was then atomized through a heated coil at 80°C into an aqueous solution over precise periods of time. Stabilizers were present in either the aqueous, organic or both phases. The dispersions were centrifuged and the supernatant was removed. Three hydrophilic stabilizers were investigated, including polysorbate 80, polyvinyl pyrrolidone and poloxamer 407. Rapid dissolving ultra-high potency of ITZ powders was successfully produced. Greater than 80% of ITZ was dissolved in 5 min compared to only 13% of ITZ bulk powders. The resulting stabilizer-coated drug particles had high drug-to-stabilizer ratios greater than 12, corresponding to potencies (wt drug/wt drug + wt surfactant) as high as 93%. An increase in dissolution rate was correlated with the amount of stabilizer adsorbed and the wettability. The combination of polysorbate 80 and poloxamer 407 present in the aqueous and organic phases, respectively, was superior in achieving high wetting and rapid dissolving ITZ powders. The ability to control the adsorption behavior of stabilizers by using synergistic combinations affords the opportunity to achieve high dissolution rates with higher potencies compared to previously reported values.
AB - The objective of this study was to investigate the influence of stabilizer type on the physicochemical properties, including dissolution, of ultra-high potency powders containing itraconazole (ITZ) formed by evaporative precipitation into aqueous solution (EPAS). ITZ was dissolved in dichloromethane, which was then atomized through a heated coil at 80°C into an aqueous solution over precise periods of time. Stabilizers were present in either the aqueous, organic or both phases. The dispersions were centrifuged and the supernatant was removed. Three hydrophilic stabilizers were investigated, including polysorbate 80, polyvinyl pyrrolidone and poloxamer 407. Rapid dissolving ultra-high potency of ITZ powders was successfully produced. Greater than 80% of ITZ was dissolved in 5 min compared to only 13% of ITZ bulk powders. The resulting stabilizer-coated drug particles had high drug-to-stabilizer ratios greater than 12, corresponding to potencies (wt drug/wt drug + wt surfactant) as high as 93%. An increase in dissolution rate was correlated with the amount of stabilizer adsorbed and the wettability. The combination of polysorbate 80 and poloxamer 407 present in the aqueous and organic phases, respectively, was superior in achieving high wetting and rapid dissolving ITZ powders. The ability to control the adsorption behavior of stabilizers by using synergistic combinations affords the opportunity to achieve high dissolution rates with higher potencies compared to previously reported values.
KW - EPAS
KW - Itraconazole
KW - Particle stabilization
KW - Stabilizer
KW - Stabilizer adsorption
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U2 - 10.1016/j.ijpharm.2005.06.027
DO - 10.1016/j.ijpharm.2005.06.027
M3 - Article
C2 - 16109466
AN - SCOPUS:24144450310
SN - 0378-5173
VL - 302
SP - 113
EP - 124
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -