Department of Pharmacy, Tangshan Maternal and Child Health Hospital, Tangshan, China.
School of Pharmacy, North China University of Science and Technology, Tangshan, China.
Drug Deliv. 2023 Dec;30(1):2183834. doi: 10.1080/10717544.2023.2183834.
In present, there was no detailed report on the formulation optimization and quality evaluation of aprepitant (APT) injectable lipid emulsion (APT-IE). The aim of the present investigation was to prepare and evaluate its properties of APT-IE loaded with an APT phospholipid complex (APT-PC) and . APT-PC was obtained by solvent evaporation with APT and phospholipids, then analyzed by -ray diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry. Lipid emulsions are a new formulation that can reduce side effects and improve drug loading.APT-IE prepared by High-pressure homogenization and optimized by response surface methodology (RSM). The proportion of sodium oleate, poloxamer 188 and soybean oil were selected as variables for the optimization. The optimal formulation of ATP-IE had the following characteristics: particle size, 82.83 ± 1.89 nm; polydispersity index, 0.243 ± 0.008; zeta potential, -59.0 ± 2.54 mV; encapsulation efficiency, 98.84%±1.43%; drug loading, 7.08 ± 0.16 mg/mL; and osmotic pressure, 301 ± 2.15 mOsmol/kg. Transmission electron microscopy images indicated that the particle diameter of APT-IE was approximately 100 nm, with a morphology of spheroidal or spherical. APT-IE exhibited sufficient stability after storage at 4 ± 2 °C for more than 6 months. The results of the pharmacokinetic study demonstrated that APT-IE had the advantages of better safety, higher bioavailability, and obvious liver targeting than APT solution (APT-SL). The area under the curve (AUC) of APT-IE was 3-fold enhanced compared with APT-SL. The targeted enhancement multiple of APT-IE to liver tissue was greater than that of APT-SL. These results suggested that APT-IE has broad clinical application and industrial production potential.
目前，尚无关于阿瑞匹坦（APT）注射用脂质乳剂（APT-IE）的制剂优化和质量评价的详细报告。本研究旨在制备并评价载有 APT 磷脂复合物（APT-PC）的 APT-IE 的性质。通过溶剂蒸发法用 APT 和磷脂制备 APT-PC，然后通过 X 射线衍射、傅里叶变换红外光谱和差示扫描量热法对其进行分析。脂质乳剂是一种新的制剂，可降低副作用并提高药物载量。采用高压匀质法制备 APT-IE，并通过响应面法（RSM）进行优化。选择油酸钠、泊洛沙姆 188 和大豆油的比例作为优化的变量。ATP-IE 的最佳配方具有以下特点：粒径为 82.83±1.89nm；多分散指数为 0.243±0.008；Zeta 电位为-59.0±2.54mV；包封效率为 98.84%±1.43%；药物载量为 7.08±0.16mg/mL；渗透压为 301±2.15mOsmol/kg。透射电子显微镜图像表明，APT-IE 的粒径约为 100nm，形态呈球形或类球形。APT-IE 在 4±2℃下储存 6 个月以上仍具有足够的稳定性。药代动力学研究结果表明，与 APT 溶液（APT-SL）相比，APT-IE 具有更好的安全性、更高的生物利用度和明显的肝靶向性。APT-IE 的曲线下面积（AUC）是 APT-SL 的 3 倍。APT-IE 对肝组织的靶向增强倍数大于 APT-SL。这些结果表明，APT-IE 具有广阔的临床应用和工业生产潜力。
