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• W1992614313 abstract "Miconazole and itraconazole possess adequate membrane permeability, but only slight water solubility, which limits their bioavailability and antifungal effect. To increase their dissolution rate, the compounds were nanoground by media milling to produce nanosuspensions with mean particle size of approximately 210 nm and stabilized with sodium dodecylsulfate (SDS) in combinations with either cellulose ethers (HPC or HPMC) or poloxamers. During storage for 3 months at 25 °C, HPC/SDS stabilized more efficiently miconazole nanoparticles, while poloxamer 407/SDS performed better with itraconazole nanosuspensions. The stabilizing efficiency of the excipients was explained by physical–chemical drug–excipients interactions. The HPC/SDS-stabilized nanosuspensions were spray-dried or freeze-dried with and without the matrix formers mannitol or microcrystalline cellulose (MCC). In absence of matrix former, itraconazole particles agglomerated more extensively than miconazole particles, resulting in a low dissolution rate. Dissolution of the spray- or freeze-dried miconazole nanosuspension was enhanced in presence of mannitol or MCC (drug substance:excipient ratio of 1:1, w/w), as compared to the coarse drug suspension (twice the amount dissolved after 10 and 20 min). Spray-drying itraconazole nanosuspension in presence of mannitol or MCC also yielded fast dissolution (60% dissolved in less than 10 min as compared to 30–45 min with the coarse suspension). Freeze-dried itraconazole nanosuspensions did generally not dissolve substantially faster than freeze-dried coarse suspension. In conclusion, we were able to process miconazole and itraconazole successfully and under similar conditions into dry nanoparticulate drug products with enhanced in vitro performance." @default.
• W1992614313 created "2016-06-24" @default.
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• W1992614313 date "2013-02-01" @default.
• W1992614313 modified "2023-10-02" @default.
• W1992614313 title "Formulation and drying of miconazole and itraconazole nanosuspensions" @default.
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• W1992614313 doi "https://doi.org/10.1016/j.ijpharm.2012.11.044" @default.
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