Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.
Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo 12622, Egypt.
Int J Pharm. 2022 Aug 25;624:122006. doi: 10.1016/j.ijpharm.2022.122006. Epub 2022 Jul 9.
Lornoxicam (LRX) is a potent nonsteroidal anti-inflammatory drug (NSAID) used extensively to manage pain and inflammatory conditions. However, the drug possesses poor aqueous solubility (i.e., BCS class II) and a short half-life (3-4 h). Mucoadhesive buccal tablets containing LRX -loaded solid lipid nanoparticles (SLNs) were developed to enhance the drug solubility and bioavailability and achieve a controlled release pattern for a better anti-inflammatory effect. Different LRX-loaded SLNs were prepared using the hot homogenization /ultra-sonication technique and evaluated using size analysis and entrapment efficiency (EE%). Optimized LRX -loaded SLNs formulation showed particle size of 216 ± 7.4 nm, zeta potential of -27.3 ± 4.6 mV, and entrapment efficiency of 92.56 ± 2.3 %. Dried LRX-loaded SLNs alongside mucoadhesive polymers blend (PVP K30 /HPMC K15) were compressed to prepare the mucoadhesive buccal tablets. The tablets showed proper physicochemical properties, good mucoadhesive strength, long mucoadhesive time, suitable pH surface, good swelling capacity, and controlled drug release profile. Furthermore, Fourier transform-infrared (FTIR) spectroscopy, Powder X-Ray diffraction (PXRD), and Scanning electron microscopy (SEM) studies were carried out. The in vivo anti-inflammatory effect of pure LRX, market LRX and optimized mucoadhesive buccal tablet of LRX -loaded SLNs (T3) against carrageenan-induced models were evaluated. T3 showed a significant and early anti-inflammatory response after 1 and 2 h (63.62-77.84 % inhibition) as well as an extended effect after 4 h as compared to pure and market LRX. In parallel, T3 showed the best amelioration of PGE2, COX2, and TNF-α serum levels after 4 h of carrageenan injection.
氯诺昔康（LRX）是一种强效的非甾体抗炎药（NSAID），广泛用于治疗疼痛和炎症性疾病。然而，该药物的水溶性差（即 BCS 分类 II），半衰期短（3-4 小时）。为了提高药物的溶解度和生物利用度，并实现更好的抗炎效果，研制了含有 LRX 载药固体脂质纳米粒（SLNs）的黏膜粘附颊片剂。使用热匀化/超声技术制备了不同的 LRX 载 SLNs，并通过粒径分析和包封效率（EE%）进行了评价。优化的 LRX 载 SLNs 制剂的粒径为 216±7.4nm，Zeta 电位为-27.3±4.6mV，包封效率为 92.56±2.3%。将干燥的 LRX 载 SLNs 与黏膜粘附聚合物（PVP K30/HPMC K15）混合压制成黏膜粘附颊片剂。该片剂具有适当的物理化学性质、良好的黏膜粘附强度、较长的黏膜粘附时间、合适的 pH 值表面、良好的溶胀能力和控释药物释放特性。此外，还进行了傅里叶变换红外（FTIR）光谱、粉末 X 射线衍射（PXRD）和扫描电子显微镜（SEM）研究。对纯 LRX、市售 LRX 和优化的 LRX 载 SLNs 黏膜粘附颊片（T3）的体内抗炎作用进行了评价，以对抗角叉菜胶诱导的模型。与纯 LRX 和市售 LRX 相比，T3 在 1 和 2 小时后（63.62-77.84%抑制）表现出显著的早期抗炎反应，并在 4 小时后表现出延长的效果。此外，T3 在角叉菜胶注射 4 小时后，对 PGE2、COX2 和 TNF-α 血清水平的改善效果最佳。
