Molecular structure and impact of amorphization strategies on intrinsic dissolution of spray dried indomethacin

TY - JOUR

T1 - Molecular structure and impact of amorphization strategies on intrinsic dissolution of spray dried indomethacin

AU - Li, Yongquan

AU - Rantanen, Jukka

AU - Yang, Mingshi

AU - Bohr, Adam

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Amorphous systems prepared with different strategies, such as solid dispersion with colloidal particles or soluble polymers and inclusion complex, have been used for improving solubility and dissolution of poorly water soluble drugs. The purpose of this study was to obtain a deeper understanding of the impact of three different amorphous systems prepared by spray drying with silica, polyvinylpyrrolidone (PVP) or 2-hydroxypropyl-β-cyclodextrin (HPβCD) using indomethacin (IND) as a model drug. IND was spray dried with silica, PVP or HPβCD at different mass ratios, and the obtained powders were characterized with respect to colloidal silica particle redispersion, morphology, thermal properties, solid state properties and physical stability. The solubility and intrinsic dissolution rate of IND in the different powders were assessed. It was found that all the three amorphization strategies resulted in amorphous IND product. PVP showed the best stabilizing effect on amorphous IND for at least four months while silica was the worst for no more than 18 days. The solubility of IND decreased with the decrease of HPβCD or PVP ratio in the amorphous products. Samples with HPβCD showed the highest improvement in the dissolution rate at low drug loading, i.e. 15% while samples with PVP resulted in the highest improvement of dissolution rate at high drug loading, i.e. 70%. We conclude that amorphization with PVP was the best strategy for amorphous IND stabilization among all the amorphous products investigated in this project and improved IND dissolution mostly at high drug loadings. HPβCD improved IND dissolution mostly at low drug loadings. Effect of solid dispersion with silica nanoparticles on the dissolution behavior was always the least significant among the three investigated amorphization strategies.

AB - Amorphous systems prepared with different strategies, such as solid dispersion with colloidal particles or soluble polymers and inclusion complex, have been used for improving solubility and dissolution of poorly water soluble drugs. The purpose of this study was to obtain a deeper understanding of the impact of three different amorphous systems prepared by spray drying with silica, polyvinylpyrrolidone (PVP) or 2-hydroxypropyl-β-cyclodextrin (HPβCD) using indomethacin (IND) as a model drug. IND was spray dried with silica, PVP or HPβCD at different mass ratios, and the obtained powders were characterized with respect to colloidal silica particle redispersion, morphology, thermal properties, solid state properties and physical stability. The solubility and intrinsic dissolution rate of IND in the different powders were assessed. It was found that all the three amorphization strategies resulted in amorphous IND product. PVP showed the best stabilizing effect on amorphous IND for at least four months while silica was the worst for no more than 18 days. The solubility of IND decreased with the decrease of HPβCD or PVP ratio in the amorphous products. Samples with HPβCD showed the highest improvement in the dissolution rate at low drug loading, i.e. 15% while samples with PVP resulted in the highest improvement of dissolution rate at high drug loading, i.e. 70%. We conclude that amorphization with PVP was the best strategy for amorphous IND stabilization among all the amorphous products investigated in this project and improved IND dissolution mostly at high drug loadings. HPβCD improved IND dissolution mostly at low drug loadings. Effect of solid dispersion with silica nanoparticles on the dissolution behavior was always the least significant among the three investigated amorphization strategies.

M3 - Journal article

SN - 0928-0987

VL - 129

SP - 1

EP - 9

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

ER -