An innovative antisolvent precipitation process as a promising technique to prepare ultrafine rifampicin particles

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• 作者：Alessandra Viç ; osa^a ; ^b ; ^c ; Jean-Jacques Letourneau^a ; Fabienne Espitalier^a ; Maria Inê ; s Ré ; ^a ; ^{maria-ines.re@mines-albi.fr}
• 关键词：A1. Antisolvent precipitation ; A1. Bioavailability enhancement ; B1. Drug nanoparticles ; B1. Poorly water-soluble drug ; B1. Rifampicin ; B1. Room temperature ionic liquids
• 刊名：Journal of Crystal Growth
• 出版年：2012
• 期刊代码：49_00220248
• 类别：ch
• 出版时间：1 March, 2012
• 卷：342
• 期：1
• 页码：80-87
• 文件大小：755 K

摘要

Many existing and new drugs fail to be fully utilized because of their limited bioavailability due to poor solubility in aqueous media (BCS drug classes II and IV). In this work, for accelerating dissolution of this kind of poorly water-soluble drugs, an antisolvent precipitation method that does not require the use of conventional volatile organic solvents is proposed. To demonstrate this technique, ultrafine particles of rifampicin were prepared using a room temperature ionic liquid (1-ethyl 3- methyl imidazolium methyl-phosphonate) as an alternative solvent and a phosphate buffer as an antisolvent.

Rifampicin solubility was measured in various solvents (1-ethyl 3-methyl imidazolium methylphosphonate, water and phosphate buffer), showing the RTIL good solvency for the model drug: rifampicin solubility was found to be higher than 90 mg/g in RTIL at 30 掳C and lower than 1 mg/g in water at 25 掳C. Additionally, it was demonstrated that introduction of rifampicin solution in 1-ethyl 3- methyl imidazolium methyl-phosphonate into the aqueous solution antisolvent can produce particles in the submicron range with or without hydroxypropyl methylcellulose as the stabilizer. The ultrafine particles (280-360 nm) are amorphous with enhanced solubility and faster dissolution rate. To our knowledge, this is the first published work examining the suitability of using RTILs for ultrafine drug nanoparticles preparation by an antisolvent precipitation process.