Enhanced Dissolution of Luteolin by Solid Dispersion Prepared by Different Methods: Physicochemical Characterization and Antioxidant Activity
Enhanced Dissolution of Luteolin by Solid Dispersion Prepared by Different Methods: Physicochemical Characterization and Antioxidant Activity
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DOI：
10.1021/acsomega.9b04075
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发表时间：
2020-03-31
期刊：
影响因子：
4.1
通讯作者：
Alanazi, Fars
中科院分区：
文献类型：
--
作者：
Alshehri, Sultan;Imam, Syed Sarim;Alanazi, Fars
木犀草素（LT）是一种难溶性生物活性化合物，口服给药后存在生物利用度问题。因此，拟议的研究工作的目的是制定和调查各种固体分散体（SD）的LT，以提高其溶解和生物活性。以聚乙二醇4000（PEG 4000）为载体，以1：1、1：2和1：4的质量比制备LT-SD。采用不同的方法制备LT-SD，包括熔融法（FU）、溶剂挥发法（SE）和微波辐射法（MI）。通过差示扫描量热法（DSC）、X射线衍射（XRD）、扫描电子显微镜（SEM）、红外（IR）光谱和核磁共振（NMR）等手段对制备的LT-SD进行了表征，并评价了其溶出度和体外抗氧化活性。DSC、XRD、SEM、IR、NMR等测试结果表明，LT-SD的形成是由于其在水溶液中的分散性。在90 min的溶出研究后，结果显示，与纯LT及其物理混合物分散体（PMD）相比，LT从制备的SD中的释放%显著更高。使用MI方法制备的LT-SD显示出LT的最大释放（即，97.78 +/- 4.41%），LT：PEG 4000质量比为1：2。使用SE方法制备的LT-SD在LT：PEG 4000的质量比为1：4时显示出93.78 +/- 3.98%的最大释放。通过MI方法制备的SD显示由于较高的水溶性和粒径的减小而增强的溶出。固态表征研究（DSC，XRD，SEM，IR和NMR研究）表明LT从结晶状态到无定形形式的形态转化。抗氧化剂的研究结果表明，形成LT-SD显示出显着更高的自由基清除活性比纯LT。因此，SD使用PEG 4000可以是一个潜在的策略，最大限度地提高溶解度，体外溶出度，和治疗效果的LT。
Luteolin (LT) is a poorly soluble bioactive compound that suffered bioavailability problems after oral administration. Hence, the aim of the proposed research work was to formulate and investigate various solid dispersions (SDs) of LT in order to enhance its dissolution and bioactivity. LT-SD was prepared using polyethylene glycol 4000 (PEG 4000) as a carrier at the mass ratios of 1:1, 1:2, and 1:4. LT-SD was prepared using different methods including fusion (FU), solvent evaporation (SE), and microwave irradiation (MI) methods. The prepared LT-SD was duly characterized in terms of differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR) and evaluated for dissolution and in vitro antioxidant activity. The results of DSC, XRD, SEM, IR, and NMR suggested the formation of LT-SD. After 90 min of the dissolution study, the results displayed that the % release of LT from prepared SD was significantly higher compared with the pure LT and its physical mixture dispersion (PMD). LT-SD prepared using the MI method displayed the maximum release of LT (i.e., 97.78 +/- 4.41%) at a 1:2 mass ratio of LT:PEG 4000. The LT-SD prepared using the SE method displayed the maximum release of 93.78 +/- 3.98% at a mass ratio of 1:4 of LT:PEG 4000. The SD prepared by the MI method showed enhanced dissolution due to higher aqueous solubility and the reduction of particle size. The solid-state characterization studies (DSC, XRD, SEM, IR, and NMR studies) suggested the morphological conversion of LT into the amorphous form from the crystalline state. The results of the antioxidant study revealed that the formation LT-SD displayed significantly higher radical scavenging activity than the pure LT. Therefore, SD obtained using PEG 4000 could be a potential strategy for maximizing the solubility, in vitro dissolution, and therapeutic efficacy of LT.