کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2503006 | 1557419 | 2011 | 9 صفحه PDF | دانلود رایگان |
Particle size reduction is a suitable method to enhance the bioavailability of poorly soluble drugs. The reduction effectiveness depends on compound properties like crystallinity, hardness and morphology. Sometimes, it is difficult to obtain small particles. To solve this problem a combinative method was developed: a combination of freeze drying with high pressure homogenization (so-called H 96 process). The freeze drying modifies the drug structure to obtain a brittle, fragile starting material for the subsequent homogenization step. Screening experiments with glibenclamide have shown a relation between the lyophilization conditions and the final particle size. Systematic investigations using design of experiment (DoE) were conducted to identify optimal process parameters. The influence of the independent variables drug concentration and organic solvent composition during freeze drying were tested by conducting a two factorial design of experiment. The model drug was dissolved in mixtures of dimethyl sulfoxide (DMSO) and tert-butanol (TBA) in different concentrations, freeze dried and subsequently homogenized at high pressure. Using optimized process conditions the particle size after 20 cycles was very small: 164 nm (z-average) and 0.114 μm (d50%). On the contrary, with unmodified drug the results were 772 nm (z-average) and 2.686 μm (d50%). It was shown, that the structure modification of the drug by means of freeze drying can significantly improve the particle size reduction effectiveness of high pressure homogenization. The study confirmed also the usefulness of DoE for nanocrystal production.
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Journal: International Journal of Pharmaceutics - Volume 420, Issue 2, 28 November 2011, Pages 395–403