Patel Pranav V, Patel Hitesh K, Panchal Shital S, Mehta Tejal A
Department of Pharmaceutics, K. B. Raval College of Pharmacy, At.Shertha, Gandhinagar .
Int J Pharm Investig. 2013 Apr;3(2):95-104. doi: 10.4103/2230-973X.114899.
Tacrolimus has poor solubility in water ranging from 4 to 12 μg/mL. The oral bio availabilities of tacrolimus is poor and exhibits high intra and inter-subject variability (4-89%, average 25%) in the liver and the kidney transplant recipients and in patients with renal impairment.
The present study deals with the development and characterization of self-micro-emulsifying drug delivery system to improve the oral bioavailability of poorly soluble drug tacrolimus.
Solubility of the tacrolimus was estimated in various oils, surfactants, and co-surfactants. Various in vitro tests such as percentage transmittance, emulsification time, cloud point, precipitation, and thermodynamic stabilities were used to find out optimized formulations. Optimized liquid self micro-emulsifying (SMEDDS) were characterized by particle size analysis and converted in solid by using the Florite RE as an adsorbent, which is further characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and particle size analysis.
The optimized liquid SMEDDS formulation contained 10% Lauroglycol FCC as an oil, 60% Cremophor RH, and 30% PEG (polyethylene glycol) 400 as a surfactant and co-surfactant respectively. The optimized liquid and solid SMEDDS showed higher drug release than the marketed capsule and pure API (active pharmaceutical ingredient) powder. For optimized liquid SMEDDS and solid SMEDDS, the globule sizes were found 113 nm and 209 nm respectively. The solid state characterization of solid-SMEDDS by SEM, DSC, FTIR, and XRD revealed the absence of crystalline tacrolimus in the solid-SMEDDS. Shelf-lives for liquid SMEDDS and solid SMEDDS were found to be 1.84 and 2.25 year respectively.
The results indicate that liquid SMEDDS and solid SMEDDS of tacrolimus, owing to nano-sized, have potential to enhance the absorption of the drug.
他克莫司在水中的溶解度很差，范围为4至12μg/mL。他克莫司的口服生物利用度较差，在肝移植和肾移植受者以及肾功能损害患者中表现出较高的个体内和个体间变异性（4 - 89%，平均25%）。
本研究旨在开发和表征自微乳化药物递送系统，以提高难溶性药物他克莫司的口服生物利用度。
评估他克莫司在各种油、表面活性剂和助表面活性剂中的溶解度。使用各种体外试验，如透光率百分比、乳化时间、浊点、沉淀和热力学稳定性，以找出优化配方。通过粒度分析对优化后的液体自微乳化（SMEDDS）进行表征，并使用弗罗里硅土RE作为吸附剂将其转化为固体，进一步通过差示扫描量热法（DSC）、扫描电子显微镜（SEM）、X射线衍射（XRD）、傅里叶变换红外光谱（FTIR）和粒度分析进行表征。
优化后的液体SMEDDS配方分别含有10%的月桂二醇FCC作为油相、60%的聚氧乙烯蓖麻油RH和30%的聚乙二醇（PEG）400作为表面活性剂和助表面活性剂。优化后的液体和固体SMEDDS显示出比市售胶囊和纯原料药（活性药物成分）粉末更高的药物释放。对于优化后的液体SMEDDS和固体SMEDDS，发现球粒尺寸分别为113nm和209nm。通过SEM、DSC、FTIR和XRD对固体SMEDDS进行的固态表征显示，固体SMEDDS中不存在结晶性他克莫司。发现液体SMEDDS和固体SMEDDS的货架期分别为1.84年和2.25年。
结果表明，他克莫司的液体SMEDDS和固体SMEDDS由于具有纳米尺寸，具有增强药物吸收的潜力。
