CU Shah College of Pharmacy, SNDT Women's University, Santacruz (W), Mumbai, 400049 Maharashtra, India.
AAPS PharmSciTech. 2009;10(3):993-1012. doi: 10.1208/s12249-009-9290-6. Epub 2009 Aug 1.
The purpose of this research was to generate, characterize, and investigate the in vivo efficacy of budesonide (BUD) microparticles prepared by spray-drying technology with a potential application as carriers for pulmonary administration with sustained-release profile and improved respirable fraction. Microspheres and porous particles of chitosan (drug/chitosan, 1:2) were prepared by spray drying using optimized process parameters and were characterized for different physicochemical parameters. Mass median aerodynamic diameter and geometric standard deviation for conventional, microspheres, and porous particles formulations were 2.75, 4.60, and 4.30 microm and 2.56, 1.75, and 2.54, respectively. Pharmacokinetic study was performed in rats by intratracheal administration of either placebo or developed dry powder inhalation (DPI) formulation. Pharmacokinetic parameters were calculated (Ka, Ke, T(max), C(max), AUC, and Vd) and these results indicated that developed formulations extended half life compared to conventional formulation with onefold to fourfold improved local and systemic bioavailability. Estimates of relative bioavailability suggested that developed formulations have excellent lung deposition characteristics with extended T(1/2) from 9.4 to 14 h compared to conventional formulation. Anti-inflammatory activity of BUD and developed formulations was compared and found to be similar. Cytotoxicity was determined in A549 alveolar epithelial cell line and found to be not toxic. In vivo pulmonary deposition of developed conventional formulation was studied using gamma scintigraphy and results indicated potential in vitro-in vivo correlation in performance of conventional BUD DPI formulation. From the DPI formulation prepared with porous particles, the concentration of BUD increased fourfold in the lungs, indicating pulmonary targeting potential of developed formulations.
本研究旨在制备布地奈德（BUD）微球，采用喷雾干燥技术，通过优化工艺参数，以壳聚糖为载体（药物/壳聚糖，1:2）制备微球和多孔颗粒，并对不同的理化参数进行了表征。常规、微球和多孔颗粒制剂的质量中值空气动力学直径和几何标准偏差分别为 2.75、4.60 和 4.30μm 和 2.56、1.75 和 2.54。通过气管内给予安慰剂或开发的干粉吸入（DPI）制剂，在大鼠中进行了药代动力学研究。计算了药代动力学参数（Ka、Ke、T(max)、C(max)、AUC 和 Vd），结果表明，与常规制剂相比，开发的制剂延长了半衰期，局部和全身生物利用度提高了 1 至 4 倍。相对生物利用度的估计表明，与常规制剂相比，开发的制剂具有出色的肺部沉积特性，T(1/2)从 9.4 小时延长至 14 小时。比较了 BUD 和开发制剂的抗炎活性，发现它们具有相似的活性。在 A549 肺泡上皮细胞系中测定了细胞毒性，发现没有毒性。采用γ闪烁照相术研究了开发的常规制剂的体内肺部沉积情况，结果表明常规 BUD DPI 制剂的体外-体内相关性良好。从制备多孔颗粒的 DPI 制剂中，肺部的 BUD 浓度增加了 4 倍，表明开发制剂具有肺部靶向潜力。
