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Molecular structure and impact of amorphization strategies on intrinsic dissolution of spray dried indomethacin
- Source :
- European Journal of Pharmaceutical Sciences. 129:1-9
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- 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.
- Subjects :
- Pyrrolidines
Materials science
Polymers
Colloidal silica
Indomethacin
Pharmaceutical Science
02 engineering and technology
030226 pharmacology & pharmacy
03 medical and health sciences
0302 clinical medicine
Drug Stability
medicine
Technology, Pharmaceutical
Solubility
Dissolution
Molecular Structure
Polyvinylpyrrolidone
biochemical phenomena, metabolism, and nutrition
Silicon Dioxide
021001 nanoscience & nanotechnology
Amorphous solid
Chemical engineering
Spray drying
Nanoparticles
Particle
Polyvinyls
Powders
0210 nano-technology
Dispersion (chemistry)
medicine.drug
Subjects
Details
- ISSN :
- 09280987
- Volume :
- 129
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....ecfc0b9920748a2d5abab4a70da04f2c