Sahu Bhanu P, Das Malay K
Acta Pol Pharm. 2014 Jan-Feb;71(1):129-37.
Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailibility of 10-90%. The aim of this study was to enhance the oral bioavailibilty of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA). These were characterized for particle size, zeta potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The average particle size of furosemide nanoparticles were found to be in the range of 150-300 nm. This was further confirmed by SEM photograph. The particle size varies with an increase in concentration of drug and stabilizer. The preparations showed negative zeta potential and polydispersity index in the range of 0.3 +/- 0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The saturation solubility of prepared furosemide nanoparticles markedly increased compared to the original drug in simulated gastric fluid. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. It may be concluded that the nanoprecipitation with ultrasonication have potential to formulate homogenous nanosuspensions with uniform sized amorphous nanoparticles of furosemide. Polyvinyl acetate can be used as a suitable steric stabilizer to prepare stable furosemide nanosuspensions. The enhanced saturation solubility in simulated gastric fluid may lead to enhanced absorption of furosemide.
呋塞米是一种弱酸性利尿剂，用于治疗水肿和高血压。它的溶解度很差，但通过胃和上消化道（GIT）的渗透性很高。由于其溶解度有限，口服生物利用度低且变化较大，为10%-90%。本研究的目的是通过制备纳米混悬液来提高呋塞米的口服生物利用度。纳米混悬液采用超声辅助纳米沉淀法制备，以二甲基亚砜（DMSO）为溶剂，水为反溶剂（NA）。制备的纳米混悬液用聚醋酸乙烯酯（PVA）进行空间稳定化。对其粒径、zeta电位、多分散指数、扫描电子显微镜（SEM）、差示扫描量热法（DSC）、X射线衍射（XRD）图谱和释放行为进行了表征。发现呋塞米纳米颗粒的平均粒径在150-300nm范围内。SEM照片进一步证实了这一点。粒径随药物和稳定剂浓度的增加而变化。制剂的zeta电位为负，多分散指数在0.3±0.1范围内。DSC和XRD研究表明，结晶呋塞米药物沉淀成纳米颗粒后转变为无定形形式。与原药物相比，制备的呋塞米纳米颗粒在模拟胃液中的饱和溶解度显著增加。纳米混悬液制剂的释放曲线显示在4小时内释放率高达81.2%。可以得出结论，超声辅助纳米沉淀法有潜力制备出均匀的呋塞米纳米混悬液，其纳米颗粒尺寸均匀且为无定形。聚醋酸乙烯酯可作为合适的空间稳定剂来制备稳定的呋塞米纳米混悬液。在模拟胃液中增强的饱和溶解度可能导致呋塞米吸收增加。
