Soltani Saieede, Zakeri-Milani Parvin, Barzegar-Jalali Mohammad, Jelvehgari Mitra
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Iran J Pharm Res. 2017 Winter;16(1):22-34.
Ketotifen fumarate is a non-bronchodilator anti-asthmatic drug which inhibits the effects of certain endogenous substances known to be inflammatory mediators, and thereby exerts antiallergic activity. The present study describes the formulation of a sustained release nanoparticle (NP) drug delivery system containing ketoftifen, using poly (D,L lactide-co-glycolide) acid (PLGA). Biodegradable NPs were prepared using 50 : 50 PLGA by a water in-oil-in-water (w/o/w) double emulsion-solvent evaporation procedure and characterized for drug content, DSC (differential scanning calorimetry, XRD (X-ray diffractionl), FTIR (Fourier transform spectroscopy), particle size , surface morphology using scanning electron microscopy, and drug release rate. The effects of different drug-to-polymer ratios on the characteristics of the NPs were investigated. NPs prepared were spherical with a smooth surface. Size of NPs was dependent on the concentration of polymer (10 mg/mL, 754.6 nm). Increasing the external organic phase volume (primary emulsion) resulted in larger particles with higher encapsulation efficiency (55%). The best drug to polymer ratio in the NP was F (1:10 ratio) which showed loading efficiency of 55%, and mean particle size of 754.6 nm, respectively. The FTIR, XRPD, and DSC results ruled out any chemical interaction between the drug and PLGA. The NPs prepared with low ratio of drug to polymer (1:5) F formulation showed faster dissolution rate than those with high drug to polymer ratio (1:10) F formulation. In conclusion, by selecting an appropriate level of the investigated parameters, spherical NPs with encapsulation efficiencies higher than 55% and a prolonged drug release over 24h (73.67-90.05%) were obtained.
富马酸酮替芬是一种非支气管扩张剂类抗哮喘药物，它能抑制某些已知为炎症介质的内源性物质的作用，从而发挥抗过敏活性。本研究描述了一种使用聚（D，L丙交酯-乙交酯）酸（PLGA）制备的含酮替芬的缓释纳米颗粒（NP）药物递送系统。采用水包油包水（w/o/w）双乳液溶剂蒸发法，以50:50的PLGA制备了可生物降解的纳米颗粒，并对其药物含量、差示扫描量热法（DSC）、X射线衍射法（XRD）、傅里叶变换光谱法（FTIR）、粒径、使用扫描电子显微镜观察的表面形态以及药物释放速率进行了表征。研究了不同药物与聚合物比例对纳米颗粒特性的影响。制备的纳米颗粒呈球形，表面光滑。纳米颗粒的大小取决于聚合物的浓度（10 mg/mL，754.6 nm）。增加外部有机相体积（初乳）会导致颗粒更大，包封效率更高（55%）。纳米颗粒中最佳的药物与聚合物比例为F（1:10比例），其负载效率为55%，平均粒径为754.6 nm。FTIR、XRPD和DSC结果排除了药物与PLGA之间的任何化学相互作用。药物与聚合物比例低（1:5）的F制剂制备的纳米颗粒比药物与聚合物比例高（1:10）的F制剂制备的纳米颗粒溶解速率更快。总之，通过选择合适水平的研究参数，获得了包封效率高于55%且药物释放时间超过24小时（73.67 - 90.05%）的球形纳米颗粒。
