Nair Anroop B, Singh Bhavna, Shah Jigar, Jacob Shery, Aldhubiab Bandar, Sreeharsha Nagaraja, Morsy Mohamed A, Venugopala Katharigatta N, Attimarad Mahesh, Shinu Pottathil
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India.
Pharmaceutics. 2022 Jan 31;14(2):336. doi: 10.3390/pharmaceutics14020336.
Being a biopharmaceutics classification system class II drug, the absorption of sertraline from the gut is mainly limited by its poor aqueous solubility. The objective of this investigation was to improve the solubility of sertraline utilizing self-nanoemulsifying drug delivery systems (SNEDDS) and developing it into a tablet dosage form. Ternary phase diagrams were created to identify nanoemulsion regions by fixing oil (glycerol triacetate) and water while varying the surfactant (Tween 80) and co-surfactant (PEG 200) ratio (S). A three-factor, two-level (2) full factorial design (batches F1-F8) was utilized to check the effect of independent variables on dependent variables. Selected SNEDDS (batch F4) was solidified into powder by solid carrier adsorption method and compressed into tablets. The SNEDDS-loaded tablets were characterized for various pharmaceutical properties, drug release and evaluated in vivo in Wistar rats. A larger isotropic region was noticed with a S ratio of 2:1 and the nanoemulsion exhibited good stability. Screening studies' data established that all three independent factors influence the dependent variables. The prepared tablets displayed optimal pharmaceutical properties within acceptable limits. In vitro sertraline release demonstrated from solid SNEDDS was statistically significant ( < 0.0001) as compared to pure sertraline. Differential Scanning Calorimetry and X-Ray Diffraction data established the amorphous state of the drug in SNEDDS formulation, while FTIR spectra indicate the compatibility of excipients and drug. Pharmacokinetic evaluation of the SNEDDS tablet demonstrated significant increment ( < 0.0001) in AUC (5-folds), C (4-folds), and relative bioavailability (386%) as compared to sertraline suspension. The current study concludes that the solid SNEDDS formulation could be a practicable and effective strategy for oral therapy of sertraline.
作为生物药剂学分类系统的II类药物，舍曲林在肠道的吸收主要受其较差的水溶性限制。本研究的目的是利用自纳米乳化药物递送系统（SNEDDS）提高舍曲林的溶解度，并将其开发成片剂剂型。通过固定油（三乙酸甘油酯）和水，同时改变表面活性剂（吐温80）和助表面活性剂（聚乙二醇200）的比例（S）来绘制三元相图，以确定纳米乳液区域。采用三因素、两水平（2³）全因子设计（批次F1 - F8）来检验自变量对因变量的影响。选择的SNEDDS（批次F4）通过固体载体吸附法固化成粉末并压制成片剂。对载有SNEDDS的片剂进行了各种药学性质、药物释放的表征，并在Wistar大鼠体内进行了评价。当S比例为2:1时，观察到较大的各向同性区域，且纳米乳液表现出良好的稳定性。筛选研究数据表明，所有三个自变量均影响因变量。制备的片剂在可接受的限度内显示出最佳的药学性质。与纯舍曲林相比，固体SNEDDS体外舍曲林释放具有统计学显著性（P < 0.0001）。差示扫描量热法和X射线衍射数据确定了SNEDDS制剂中药物的无定形状态，而傅里叶变换红外光谱表明辅料与药物具有相容性。与舍曲林混悬液相比，SNEDDS片剂的药代动力学评价显示AUC（约5倍）、Cmax（约4倍）和相对生物利用度（386%）有显著增加（P < 0.0001）。本研究得出结论，固体SNEDDS制剂可能是舍曲林口服治疗的一种可行且有效的策略。
