Palmeiro-Roldán Ricardo, Fonseca-Berzal Cristina, Gómez-Barrio Alicia, Arán Vicente J, Escario José A, Torrado-Durán Susana, Torrado-Santiago Santiago
Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
CEI Campus Moncloa, UCM-UPM & CSIC, Madrid, Spain; Department of Parasitology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
Int J Pharm. 2014 Sep 10;472(1-2):110-7. doi: 10.1016/j.ijpharm.2014.06.015. Epub 2014 Jun 10.
This work aims to develop novel benznidazole (BZN) solid dispersions (SD) to improve its solubility and bioavailability properties. Low-substituted hydroxypropylcellulose (L-HPC) and sodium deoxycholate (NaDC) were evaluated as carriers. BZN solid dispersions containing different ratios of carrier were prepared by a freeze-drying process and characterized by SEM, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution studies. The reduced BNZ crystallinity in the new formulations was confirmed by XRD, and supported by DSC. BNZ:L-HPC solid dispersion at a 1:3 ratio (w/w) (SD-1:3 L-HPC) improved the BNZ dissolution rate (85% at 5 min) in comparison with BNZ raw material (23% at 5 min). However, NaDC formulations showed a prolonged release (24% at 30 min for SD-1:3 NaDC), due to the formation of a sustained release matrix in acidic medium. In vivo studies performed in a murine model of Chagas disease showed that the formulation achieving the highest parasitemia suppression at a low dose of 25mg/kg/day after five days of treatment was SD-1:3 L-HPC (60% of parasitemia suppression versus 33% of suppression exerted by BNZ), suggesting that BNZ:L-HPC systems enhance the bioavailability of the drug.
本研究旨在开发新型苯硝唑（BZN）固体分散体（SD），以改善其溶解度和生物利用度。评估了低取代羟丙基纤维素（L-HPC）和脱氧胆酸钠（NaDC）作为载体。通过冷冻干燥法制备了含有不同载体比例的BZN固体分散体，并通过扫描电子显微镜（SEM）、粉末X射线衍射（XRD）、差示扫描量热法（DSC）和溶出度研究对其进行了表征。XRD证实了新制剂中BNZ结晶度的降低，并得到了DSC的支持。与BZN原料药（5分钟时为23%）相比，1:3比例（w/w）的BNZ:L-HPC固体分散体（SD-1:3 L-HPC）提高了BNZ的溶出速率（5分钟时为85%）。然而，由于在酸性介质中形成了缓释基质，NaDC制剂显示出缓释效果（SD-1:3 NaDC在30分钟时为24%）。在恰加斯病小鼠模型中进行的体内研究表明，在25mg/kg/天的低剂量治疗5天后，实现最高寄生虫血症抑制率的制剂是SD-1:3 L-HPC（寄生虫血症抑制率为60%，而BZN为33%），这表明BNZ:L-HPC体系提高了药物的生物利用度。
