TY - JOUR
T1 - Impact of polymers on the aggregation of wet-milled itraconazole particles and their dissolution from spray-dried nanocomposites
AU - Bilgili, Ecevit
AU - Rahman, Mahbubur
AU - Palacios, Danny
AU - Arevalo, Faustin
N1 - Funding Information:
We gladly appreciate financial support from Nisso America Inc. Thanks are extended to Dow Chemical and BASF Corporation for donating us the polymer samples. We would like to thank Prof. Murat Guvendiren and Dr. Chya-Yan Liaw of NJIT for their help with the use of their Kinexus Ultra Plus Rotational Rheometer and performing rheological characterization of the dispersant solutions.
Publisher Copyright:
© 2018 The Society of Powder Technology Japan
PY - 2018/12
Y1 - 2018/12
N2 - We explore the impact of various polymers and their molecular weight on the stabilization of wet-milled suspensions of itraconazole (ITZ), a poorly soluble drug, and its dissolution from spray-dried suspensions. To this end, ITZ suspensions with SSL, SL, and L grades of hydroxypropyl cellulose (HPC) having molecular weights (MWs) of 40, 100, and 140 kg/mol, respectively, hydroxypropyl methyl cellulose (HPMC E3 with 10 kg/mol), polyvinylpyrrolidone (PVP K30 with 50 kg/mol), sodium dodecyl sulfate (SDS, surfactant), and HPC SL–SDS were wet media milled and spray-dried. Laser diffraction results show that 2.5% HPC SL–0.2% SDS led to the finest ITZ nanosuspension, whereas without SDS, only 4.5% HPC with SL/L grades ensured minimal aggregation. Rheological characterization reveals that aggregated suspensions exhibited pronounced pseudoplasticity, whereas stable suspensions exhibited near Newtonian behavior. Spray-drying yielded nanocomposites with 60–78% mean ITZ loading and acceptable content uniformity. Severe aggregation occurred during milling/drying when 4.5% polymers with MW ≤ 50 kg/mol were used; their nanocomposites exhibited incomplete redispersion due to slow matrix erosion and released ITZ slowly during dissolution test. Overall, high drug-loaded, surfactant-free ITZ nanocomposites that exhibited immediate release (>80% dissolved in 20 min) were prepared via spray-drying of wet-milled ITZ with 4.5% HPC SL/L.
AB - We explore the impact of various polymers and their molecular weight on the stabilization of wet-milled suspensions of itraconazole (ITZ), a poorly soluble drug, and its dissolution from spray-dried suspensions. To this end, ITZ suspensions with SSL, SL, and L grades of hydroxypropyl cellulose (HPC) having molecular weights (MWs) of 40, 100, and 140 kg/mol, respectively, hydroxypropyl methyl cellulose (HPMC E3 with 10 kg/mol), polyvinylpyrrolidone (PVP K30 with 50 kg/mol), sodium dodecyl sulfate (SDS, surfactant), and HPC SL–SDS were wet media milled and spray-dried. Laser diffraction results show that 2.5% HPC SL–0.2% SDS led to the finest ITZ nanosuspension, whereas without SDS, only 4.5% HPC with SL/L grades ensured minimal aggregation. Rheological characterization reveals that aggregated suspensions exhibited pronounced pseudoplasticity, whereas stable suspensions exhibited near Newtonian behavior. Spray-drying yielded nanocomposites with 60–78% mean ITZ loading and acceptable content uniformity. Severe aggregation occurred during milling/drying when 4.5% polymers with MW ≤ 50 kg/mol were used; their nanocomposites exhibited incomplete redispersion due to slow matrix erosion and released ITZ slowly during dissolution test. Overall, high drug-loaded, surfactant-free ITZ nanocomposites that exhibited immediate release (>80% dissolved in 20 min) were prepared via spray-drying of wet-milled ITZ with 4.5% HPC SL/L.
KW - Dissolution enhancement
KW - Drug nanoparticles
KW - Polymers
KW - Spray drying
KW - Wet media milling
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U2 - 10.1016/j.apt.2018.09.039
DO - 10.1016/j.apt.2018.09.039
M3 - Article
AN - SCOPUS:85054873871
SN - 0921-8831
VL - 29
SP - 2941
EP - 2956
JO - Advanced Powder Technology
JF - Advanced Powder Technology
IS - 12
ER -