Christian Ruby, Thakkar Vaishali, Patel Tushar, Gohel Mukesh, Baldaniya Lalji, Shah Purvi, Pandya Tosha, Gandhi Tejal
Department of Pharmaceutics, Anand Pharmacy College, Anand- 388 001, Gujarat, India.
Curr Drug Deliv. 2019;16(1):66-78. doi: 10.2174/1567201815666180927155710.
The focus of this study was to develop in situ injectable implants of Lornoxicam which could provide sustained drug release.
Biodegradable in situ injectable implants were prepared by polymer precipitation method using polylactide-co-glycolide (PLGA). An optimized formulation was obtained on the basis of drug entrapment efficiency, gelling behavior and in vitro drug release. The compatibility of the formulation ingredients were tested by Fourier transform infrared (FT-IR) spectroscopy, and differential scanning colorimetry (DSC). SEM study was performed to characterize in vivo behavior of in situ implant. Pharmacokinetic study and in vivo gelling study of the optimized formulation were performed on Sprague-Dawley rats. Stability testing of optimized formulation was also performed.
The drug entrapment efficiency increased and burst release decreased with an increase in the polymer concentration. Sustained drug release was obtained up to five days. SEM photomicrographs indicated uniform gel formation. Chemical interaction between the components of the formulation was not observed by FT-IR and DSC study. Pharmacokinetic studies of the optimized formulation revealed that the maximum plasma concentration (Cmax), time to achieve Cmax (Tmax) and area under plasma concentration curve (AUC) were significantly higher than the marketed intramuscular injection of lornoxicam. Stability study of optimized batch showed no change in physical and chemical characteristics.
Lornoxicam can be successfully formulated as in situ injectable implant that provides long-term management of inflammatory disorders with improved patient compliance.
本研究的重点是开发能够实现洛索洛芬钠持续药物释放的原位注射植入剂。
采用聚乳酸-羟基乙酸共聚物（PLGA）通过聚合物沉淀法制备可生物降解的原位注射植入剂。基于药物包封率、凝胶化行为和体外药物释放获得了优化配方。通过傅里叶变换红外（FT-IR）光谱和差示扫描量热法（DSC）测试配方成分的相容性。进行扫描电子显微镜（SEM）研究以表征原位植入剂的体内行为。在Sprague-Dawley大鼠上进行优化配方的药代动力学研究和体内凝胶化研究。还对优化配方进行了稳定性测试。
随着聚合物浓度的增加，药物包封率提高，突释减少。实现了长达五天的持续药物释放。SEM显微照片表明形成了均匀的凝胶。FT-IR和DSC研究未观察到配方成分之间的化学相互作用。优化配方药代动力学研究表明，最大血浆浓度（Cmax）、达到Cmax的时间（Tmax）和血浆浓度曲线下面积（AUC）显著高于市售的洛索洛芬钠肌肉注射剂。优化批次的稳定性研究表明物理和化学特性没有变化。
洛索洛芬钠可以成功配制成原位注射植入剂，为炎症性疾病提供长期治疗，提高患者依从性。
