环糊精包合特性及包合常数的测定和预测

介绍了环糊精-药物包合物的特性,包括包合热力学特性、包合增溶的优势,着重介绍包合常数对药物-环糊精包合的指导意义及其测定和预测方法。     

辣椒碱-β-环糊精包合物的研制及包合常数的测定

目的制备辣椒碱-β-环糊精包合物,考察其溶解度。方法采用共沉淀法制备包合物,用正交设计优化包合物形成的最佳条件,采用相溶解度法测定包合物的表观溶解度和包合稳定常数。结果通过正交试验筛选的最优条件为包合时间6 h,搅拌强度70 rpm,包合温度70℃,辣椒碱与β-环糊精质量比为1:21,溶液p H值为11。在25、37、45℃条件下包合物中辣椒碱的溶解度极大值分别为0.32、0.60、1.08 mg·m L-1。结论辣椒碱与β-环糊精能形成稳定的包合物,制成包合物后辣椒碱的溶解度增加。     

环糊精及其衍生物的药学应用进展

环糊精及其衍生物通过非共价结合的包合作用或与药物形成共轭化合物,在提高溶解效率、改善药剂性能和方便药物传输等方面得到了广泛的应用.近年来,环糊精及其衍生物还被用作治疗性基因载体和某些蛋白质生物大分子的新型药物制剂材料,从而开辟了一个崭新的前沿研究领域.     

香草醛/环糊精包合性能研究

目的:研究环糊精对香草醛的包合性能。方法:采用紫外分光光度法研究香草醛／环糊精包合作用;研磨法制备包合物;差示热分析和1H-NMR验证包合物;紫外分光光度法考察包合物的溶解度;影响因素实验和加速实验验证包合物的稳定性。结果:香草醛与环糊精可形成1:1的稳定包合物,包合常数为1 063-13 793 L·mol-1,37℃下包合物使香草醛的溶解度增加14．43倍,包合物稳定性大大增强。结论:环糊精能明显增加香草醛溶解度、增强其稳定性,该技术对香草醛制剂的改进具有应用价值。     

环糊精包合技术及其在中药药剂中的应用

目的探讨环糊精包合技术及其在中药药剂中的应用。方法随机抽取近几年来环糊精包合技术及其在中药药剂中的应用的资料作为研究对象进行综合分析。结果环糊精包合技术及其在中药药剂中的应用具有抑制药物挥发、降低药物刺激性、减少药物不良反应的效果，大大提高药物的溶解度和药物稳定性。结论环糊精包合技术及其在中药药剂中的应用，效果良好，值得临床应用与推广。     

葛根素/β-环糊精包合物的初步研究

目的:制备葛根素／β-环糊精包合物,并考察其溶解度。方法:用捏合法制备葛根素／β-环糊精包合物,采用紫外光谱法和相溶解度法研究包合过程,差示扫描量热分析、X-衍射、1H-NMR验证包合物,并测定了包合物的溶解度。结果:葛根素与β-环糊精可形成1:1(物质的量比)的稳定包合物,包合常数398 L·mol-1。37℃下包合物使葛根素的溶解度增加5．55倍。结论:β-环糊精对葛根素增溶作用明显,适用于葛根素口服制剂的改进。     

伏立康唑与羟丙基-β-环糊精包合常数的测定

目的测定伏立康唑的羟丙基-β-环糊精包合物的包合常数。方法以伏立康唑为模型药物,采用相溶解度法测定伏立康唑与羟丙基-β-环糊精的包合常数。结果伏立康唑的羟丙基-β-环糊精的包合常数为162.5 L/mol,伏立康唑的相溶解度与羟丙基-β-环糊精的摩尔浓度成正比。结论伏立康唑的羟丙基-β-环糊精包合物可用于静脉注射。     

环糊精包合技术及其在中药药剂中的应用

环糊精作为一种新型辅料,已经被广泛应用于制药领域。环糊精包合技术在中药领域已有较普遍的应用和研究,其可以提升药物稳定性,增加难溶性药物溶解度和生物利用度,减少药物的副作用和刺激性,使液态药物粉末化,掩盖药物臭味,防止药物挥发,达到提高疗效等目的,在开发研制药物新剂型,新品种方面有着良好的应用前景。     

卡马西平β-环糊精包合物的制备及其包合作用的考察

目的为提高卡马西平的溶解性,采用饱和水溶液法制备卡马西平β-环糊精包合物并对其工艺和包合作用进行研究。方法以包封率、收率、载药量为指标,采用综合评分法,通过正交设计优选最佳包合工艺。采用连续递变浓度法测定包合比,绘制不同温度下的相溶解度曲线,测定包合常数和热力学参数。结果最佳包合工艺为包合温度80℃,卡马西平与β-环糊精物质的量比为1∶1,包合时间为1 h。所测定的包合物的包封率为93%,收率为98.6%,载药量为16%。相溶解度曲线为AL型,于25、35、45和55℃下包合常数分别为499.8、673.2、916.9和1 240.8 L·mol-1,吉布斯自由能(ΔG)分别为-15.4、-16.7、-18.0和-19.4 k J·mol-1,焓变(ΔH)为24.7 k J·mol-1,熵变(ΔS)为134.3 J·mol-1·K-1。结论所制备的卡马西平β-环糊精包合物,溶解性显著提高,包合过程是自发进行的熵驱动下的吸热反应。     

环糊精包合技术研究进展

环糊精（CD）因其特殊的分子结构，能与许多药物形成包合物。药物制成CD包合物后，其溶解度、生物利用度、化学稳定性、刺激性等某一或几方面有明显的改善，因此CD在药物制剂方面有着重要的应用价值。在归纳分析大量文献的基础上结合笔者的研究体会，本文重点综述了CD包合技术的研究进展。     

溶液中环糊精及其衍生物与药物相互作用的光谱学研究

从光谱增敏现象、包合作用的影响因素和对药物光谱学的影响机制及包合物的光谱学应用等诸方面，综述近年来关于药物与环糊精相互作用的光谱学研究。     

Enmein的平衡溶解度、油水分配系数及环糊精包合作用的研究

目的 测定Enmein的平衡溶解度、油水分配系数,考察环糊精对其包合作用,为制剂研究奠定基础。方法 采用HPLC测定Enmein在不同溶剂中的平衡溶解度;采用摇瓶法测定Enmein在不同条件下的油水分配系数;以羟丙基-β-环糊精（HP-β-CD）、羟丙基-γ-环糊精（HP-γ-CD）2种材料制备Enmein包合物,经溶解度试验,比较溶解性能的变化。结果 （25±0.5）℃振摇24 h,Enmein在纯水中溶解度为（239.32±4.99）μg·mL^-1,在多种常见的有机溶剂中微溶,在常用的药用油溶剂中不溶;正辛醇-水体系中,测得Enmein油水分配系数P为4.64,不同生理pH环境及环糊精材料,对其lgP影响不大;经过2种材料包合后,Enmein的溶解度有所提高,其中以HP-γ-CD的增溶效果最好。结论 Enmein在水、常见的药用油溶剂中溶解性均不好;消化道生理pH变化及包合材料对Enmein的吸收影响不大;用Enmein的HP-γ-CD包合物为原料制备制剂,有利于提高其生物利用度。     

Inclusion complexes of tadalafil with natural and chemically modified β-cyclodextrins. I: Preparation and in-vitro evaluation

The aim of this work was to investigate the inclusion complexation between tadalafil, a practically insoluble selective phosphodiesterase-5 inhibitor (PDE5), and two chemically modified β-cyclodextrins: hydroxypropyl-β-cyclodextrin (HP-β-CD) and heptakis-[2,6-di-O-methyl]-β-cyclodextrin (DM-β-CD), in comparison with the natural β-cyclodextrin (β-CD) in order to improve the solubility and the dissolution rate of the drug in an attempt to enhance its bioavailability. Inclusion complexation was investigated in both the solution and the solid state. The UV spectral shift method indicated guest–host complex formation between tadalafil and the three cyclodextrins (CDs). The phase solubility profiles with all the used CDs were classified as A_p-type, indicating the formation of higher order complexes. The complexation efficiency values (CE), which reflect the solubilizing power of the CDs towards the drug, could be arranged in the following order: DM-β-CD > HP-β-CD > β-CD. Solid binary systems of tadalafil with CDs were prepared by kneading and freeze-drying techniques at molar ratios of 1:1, 1:3 and 1:5 (drug to CD). Physical mixtures were prepared in the same molar ratios for comparison. Physicochemical characterization of the prepared systems at molar ratio of 1:5 was studied using differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and Fourier-transform infrared spectroscopy (FTIR). The results showed the formation of true inclusion complexes between the drug and both HP-β-CD and DM-β-CD using the freeze-drying method at molar ratio of 1:5. In contrast, crystalline drug was detectable in all other products. The dissolution of tadalafil from all the prepared binary systems was carried out to determine the most appropriate CD type, molar ratio, and preparation technique to prepare inclusion complexes to be used in the development of tablet formulation for oral delivery of tadalafil. The dissolution enhancement was increased on increasing the CD proportion in all the prepared systems. Both the CD type and the preparation technique played an important role in the performance of the system. Irrespective of the preparation technique, the systems prepared using HP-β-CD and DM-β-CD yielded better performance than the corresponding ones prepared using β-CD. In addition, the freeze-drying technique showed superior dissolution enhancement than other methods especially when combined with the β-CD derivatives.     

Theoretical and experimental vibrational study of miconazole and its dimers with organic acids: application to the IR characterization of its inclusion complexes with cyclodextrins

The geometry, frequency and intensity of the vibrational bands of miconazole were derived from the density functional theory (DFT) calculations with the hybrid functional B3LYP and the 6-31G(d) basis set. Starting from the fully AM1 optimized geometries of miconazole/βCD/acids complexes, the miconazole/acid dimers were reoptimized at the B3LYP/6-31G(d) level. Three acids were studied: maleic, fumaric and l-tartaric acids. To begin with the vibrational spectral data obtained from solid phase in mid FT-IR spectrum of miconazole and its dimers are assigned based on the results of the normal modes calculations. All the observed spectra and the calculated ones are found to be in good agreement. In a second step, theoretical results allowed the assignment of FT-IR spectrum for the miconazole/HPγCD inclusion complex produced by supercritical carbon dioxide treatment and confirmed the inclusion of miconazole. The experimental spectra for the miconazole/HPγCD/acids complexes prepared by supercritical carbon dioxide processing were also assigned using theoretical results. The results confirmed the presence of a genuine inclusion complex and also the interaction between miconazole and the acid.