Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2024-09-14 DOI:10.1016/j.ijpx.2024.100284
Pierre A. Hanna , Hatim A. Al-Abbadi , Mohamed A. Hashem , Aziza E. Mostafa , Yasmina K. Mahmoud , Eman A. Ahmed , Ibrahim M. Hegab , Ibrahim E. Helal , Mahmoud F. Ahmed
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Abstract

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t1/2 and AUC024 and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

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开发新型肌肉注射脂质体,用于美洛昔康的高级给药:骨科疼痛模型的制备、表征、体内药代动力学、药效学和疼痛评估
疼痛会产生多种生理和退行性并发症。本研究旨在将美洛昔康(MLX)配制成脂质体,以增加其溶解度,并以可控方式递送 MLX,从而克服其水溶性差和 t1/2 较短的问题。脂质体的制备方法是薄膜水合,然后进行超声处理。表征制剂特性的测试包括粒度、跨度、夹持效率、载药量、稳定性、差示扫描量热法(DSC)、傅立叶变换红外光谱法(FT-IR)、形态学、体外释放、释放动力学数学建模,以及在接受骨科手术的狗身上进行的体内疼痛模型试验,随后进行了体内药代动力学、药效学和疼痛评估研究,并与参考标准 Mobitil® 进行了比较。脂质体 MLX 的粒径约为 100 纳米,包埋效率为 82%,药物负载率为 4.62%。稳定性研究、DSC 和傅立叶变换红外光谱显示,脂质体具有很高的稳定性。与 Mobitil® 相比,该制剂的体外控释模式得到了改善,体内药代动力学行为也得到了增强,表现为更高的 t1/2、AUC0-24 和更低的 Cl/F。药效学研究和疼痛量表显示,脂质体 MLX 比 Mobitil® 能更好地控制术后疼痛。总之,在脂质体中加入 MLX 可提高其溶解度和稳定性,以及镇痛特性。
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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
期刊介绍: International Journal of Pharmaceutics: X offers authors with high-quality research who want to publish in a gold open access journal the opportunity to make their work immediately, permanently, and freely accessible. International Journal of Pharmaceutics: X authors will pay an article publishing charge (APC), have a choice of license options, and retain copyright. Please check the APC here. The journal is indexed in SCOPUS, PUBMED, PMC and DOAJ. The International Journal of Pharmaceutics is the second most cited journal in the "Pharmacy & Pharmacology" category out of 358 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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