Faculty of Pharmacy, Interdisciplinary Excellence Centre, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary; Faculty of Pharmaceutical Sciences, The Hashemite University, 13133 Zarqa, Jordan.
Faculty of Pharmacy, Interdisciplinary Excellence Centre, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary.
Int J Pharm. 2020 Apr 15;579:119166. doi: 10.1016/j.ijpharm.2020.119166. Epub 2020 Feb 19.
The unique requirements of poorly water-soluble drug delivery have driven a great deal of research into new formulations and routes of administration. This study investigates the use of nanosuspensions for solubility enhancement and drug delivery. Simple methods were used to prepare nasal formulations of loratadine based on nanosuspension pre-dispersion with sodium hyaluronate as a mucoadhesive agent. The nanosuspension was prepared by antisolvent precipitation method followed by ultrasonication and characterized for particle size, polydispersity index, zeta potential, morphology, and structure. Moreover, the nasal formulations were characterized for drug loading, pH, particle size, viscosity, bioadhesive viscosity parameter, and were evaluated for in vitro dissolution and diffusion, in addition to in vivo studies in a rat model. Loratadine nanosuspension displayed a particle size of 311 nm, a polydispersity index of 0.16, and zeta potential of -22.05 mV. The nanosuspension preserved the crystalline status of the raw drug. The addition of sodium hyaluronate exhibited an increase in the mean particle size and zeta potential of the nanoparticles. The nasal formulations showed enhanced bioadhesive properties compared to the unprocessed loratadine in the reference samples. The nanosuspension based-formulation that contained 5 mg mL sodium hyaluronate and 2.5 mg mL loratadine (NF4) showed a significant enhancement of flux and permeability coefficient through a synthetic membrane. NF4 exhibited 24.73 µg cm h and 0.082 cm h, while the reference sample showed 1.49 µg cm h and 0.017 cm h, for the flux and the permeability coefficient, respectively. Nasal administration of NF4 showed a bioavailability of 5.54-fold relative to the oral administration. The results obtained in this study indicate the potential of the nasal route and the nanosuspension for loratadine delivery. The relative bioavailability of NF4 was 1.84-fold compared to unprocessed loratadine in the reference sample. Therefore, the nanosized loratadine could be suggested as a practical and simple nanosystem for the intranasal delivery with improved bioavailability.
对于水溶性差的药物输送的独特要求，推动了对新制剂和给药途径的大量研究。本研究探讨了纳米混悬剂在提高溶解度和药物传递方面的应用。采用简单的方法，基于纳米混悬液预先分散，以透明质酸钠作为粘膜粘附剂，制备了氯雷他定的鼻用制剂。纳米混悬剂通过反溶剂沉淀法制备，然后进行超声处理，并对粒径、多分散指数、Zeta 电位、形态和结构进行了表征。此外，还对鼻用制剂的药物载量、pH 值、粒径、粘度、生物粘附粘度参数进行了表征，并进行了体外溶解和扩散评价，以及在大鼠模型中的体内研究。氯雷他定纳米混悬液显示出 311nm 的粒径、0.16 的多分散指数和-22.05mV 的 Zeta 电位。纳米混悬液保留了原料药的结晶状态。透明质酸钠的加入使纳米粒子的平均粒径和 Zeta 电位增加。与参考样品中的未加工氯雷他定相比，鼻用制剂表现出增强的生物粘附特性。含有 5mg/mL 透明质酸钠和 2.5mg/mL 氯雷他定的纳米混悬剂制剂（NF4）在通过合成膜时表现出显著增加的通量和渗透系数。NF4 的通量和渗透系数分别为 24.73µg·cm h 和 0.082cm·h，而参考样品的通量和渗透系数分别为 1.49µg·cm h 和 0.017cm·h。NF4 的鼻腔给药相对于口服给药的生物利用度提高了 5.54 倍。本研究结果表明，鼻腔给药途径和纳米混悬剂在氯雷他定传递方面具有潜力。NF4 的相对生物利用度与参考样品中的未加工氯雷他定相比提高了 1.84 倍。因此，纳米尺寸的氯雷他定可以被建议作为一种实用且简单的纳米系统，用于提高生物利用度的鼻内给药。
