杨梅素固体分散体的制备以及体外溶出试验

目的运用固体分散技术制备杨梅素固体分散体并提高其体外溶出速率。方法选用PEG6000和PVPK30为载体,采用溶剂法和溶剂-熔融法制备杨梅素固体分散体,采用紫外分光光度法进行含量测定,并进行溶解度、体外溶出试验。结果两种载体的固体分散体均能增加药物的溶解度和溶出速率,杨梅素在载体中以高度分散状态存在。结论以PVPK30为载体的杨梅素固体分散体体外溶解度和溶出速率明显提高。杨梅素固体分散体能显著提高杨梅素的溶出速率。     

他达那非固体分散体的制备和性质研究

目的制备他达那非(tadalafil,TD)固体分散体并进行性质研究。方法利用喷雾干燥法制备固体分散体,以表观溶解度和溶出度为指标筛选处方,采用差示扫描量热(DSC)、粉末X-射线衍射(PXRD)和接触角测定等技术研究药物的存在状态和润湿性等理化性质。结果固体分散体将他达那非的表观溶解度提高22.6倍;20min内药物的累积溶出超过90%;固体分散体药物以分子或无定形状态存在;接触角减小,润湿性增大。结论采用十二烷基硫酸钠(SDS)和介孔硅为载体制备的他达那非固体分散体,能明显提高药物的表观溶解度和溶出度。     

Improvement of solubility and dissolution rate of indomethacin by solid dispersions in Gelucire 50/13 and PEG4000

The aim of this study was to prepare and characterize solid dispersions of water insoluble non-steroidal anti-inflammatory drug, indomethacin (IND), with polyethylene glycol 4000 (PEG4000) and Gelucire 50/13 (Gelu.) for enhancing the dissolution rate of the drug. The solid dispersions (SDs) were prepared by hot melting method at 1:1, 1:2 and 1:4 drug to polymer ratios. Scanning electron microscopy (SEM), X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC) were used to examine the physical state of the drug. Furthermore, the solubility and the dissolution rate of the drug in its different systems were explored. The data from the XRD showed that the drug was still detectable in its solid state in all SDs of IND–Gelu. and disappeared in case of higher ratio of IND–PEG4000. DSC thermograms showed the significant change in melting peak of the IND when prepared as SDs suggesting the change in crystallinity of IND. The highest ratio of the polymer (1:4) enhanced the drug solubility about 4-folds or 3.5-folds in case of SDs of IND–PEG or IND–Gelu., respectively. An increased dissolution rate of IND at pH 1.2 and 7.4 was observed when the drug was dispersed in these carriers in form of physical mixtures (PMs) or SDs. IND released faster from the SDs than from the pure crystalline drug or the PMs. The dissolution rate of IND from its PMs or SDs increased with an increasing amount of polymer.     

熔融法制备布洛芬固体分散体

目的提高布洛芬的体外溶出速率。方法以亲水性Sylysia 730为载体,采用熔融法制备布洛芬-Sylysia 730固体分散体;利用体外溶出度实验确定熔融法制备固体分散体的制备条件;采用粉末X射线衍射法、差示扫描量热法、扫描电子显微镜分析法对制备的固体分散体进行物相鉴别。结果熔融法制备的布洛芬-Sylysia 730固体分散体中布洛芬均以非晶态存在于载体中。结论用Sylysia 730制备布洛芬固体分散体后显著提高了布洛芬的溶出速率,可进一步进行体内释药行为考察。     

超临界二氧化碳流体制备拉帕替尼固体分散体的考察

目的 采用超临界二氧化碳(CO2)流体制备拉帕替尼固体分散体,提高拉帕替尼的体外溶出度.方法 考察载体种类、药载比、工艺条件(压力、温度、制备时间)对固体分散体中拉帕替尼溶出情况的影响,筛选制备工艺.结果 工艺条件为45℃、20 MPa、2 h时,药载量为35%的拉帕替尼-Soluplus固体分散体的溶出速率较原料药显著提高,在pH=1.0介质中90 min溶出率约97%.由差示扫描量热法和粉末X射线衍射法分析可知,拉帕替尼以无定形状态和微晶态分散于载体中.结论采用超临界CO2法制备的拉帕替尼-Soluplus固体分散体的体外溶出度较拉帕替尼原料药明显提高,工艺简单,为其工业化生产提供了基础.     

超临界抗溶剂技术制备对乙酰氨基酚-PEG4000固体分散体

以水难溶药物对乙酰氨基酚为模型体系，研究了超临界二氧化碳抗溶剂法(PCA和GAS)制备乙酰氨基酚-PEG分散体微细颗粒的影响因素，用电子扫描显微镜、X射线衍射仪和示差扫描量热仪研究了颗粒的物理性质，发现经PCA和GAS处理后，颗粒分散性增强，与水的接触面积增大，溶出速度和溶出量均随之增大。研究表明．超临界抗溶剂过程是制备固体分散体的一个可行的方法。     

Experimental and mesoscale computational dynamics studies of the relationship between solubility and release of quercetin from PEG solid dispersions

The flavonol quercetin is potentially clinically relevant for its antimicrobial, beneficial cardiovascular effects, cancer treatment amongst others. However, its successful therapeutic application is severely curtailed by its poor water solubility and poor absorption following oral administration. In this study, solid dispersions of quercetin in poly(ethylene glycol) (PEG) at various compositions demonstrated an increase in the solubility, however with time, dissolution profiles show a decrease in dissolved flavonol concentration. The mechanism by which this decrease in solubility occurs was studied experimentally as well as by computational mesocscale particle dynamics simulations. The results suggest that phase separation of the polymer and flavonol during release from the solid dispersion is responsible for the time-dependent decrease in dissolved quercetin. It is suggested that the increase in release of quercetin in a PEG solid dispersion would only be beneficial if it were administered at the site of absorption, e.g. rectal administration, to ensure absorption prior to phase separation. The solid dispersions presented here would greatly improve the pharmaceutical availability of the flavonol at the site of absorption. Computational mesoscopic modeling was successfully applied to study the solid dispersions and corroborate experimental findings.     

吲哚美辛固体分散体的制备和理化性质的研究

目的:研究吲哚美辛(IMC)固体分散体的理化性质,提高IMC的溶出速度。方法:用溶剂法制备固体分散体,用粉末X射线衍射研究原型药物、载体、固体分散体(比例1∶1～1∶5)的物态性质,考察药物在分散体中溶出行为的改变。结果:制得的固体分散体大大提高了IMC的溶出速度,5min内溶出了将近100%的药物。结论:通过溶剂法,成功制备了IMC的固体分散体,药物在分散体中以无定型的状态存在,在溶出介质中药物能够迅速溶出。     

酮洛芬-聚乙烯吡咯烷酮固体分散物的制备及其体外溶出度的研究

目的提高难溶性药物酮洛芬体外溶出速度。方法以聚乙烯吡咯烷酮(PVPK30)为载体,制备药物与载体不同比例的固体分散物及物理混合物,采用X射线衍射和红外吸收方法,比较二者及药物的结晶形态,并进行体外药物溶出度的测定。结果固体分散物体外溶出速率明显高于物理混合物及酮洛芬原料的体外溶出速度,且随载体比例增加而增大。固体分散物的X射线衍射及红外吸收图谱确定了酮洛芬以无定形态分散在载体中,放置6个月后,固体分散物X射线衍射图谱没有明显变化。结论药物与载体以合适比例制备的固体分散物可以明显提高药物体外溶出速度。     

他克莫司固体分散体的制备及体外溶出度测定

目的:制备他克莫司固体分散体,提高他克莫司的体外溶出度。方法:以体外溶出度为指标,从泊洛沙姆188(Poloxamer188)、聚维酮K30(PVP K30)、羟丙甲纤维素(HPMCE3)、聚乙二醇6000(PEG6000)中筛选最优载体及其比例。并采用差示热量扫描(DSC)、红外光谱(FTIR)、电子扫描电镜(SEM)等进行物相表征。结果:4种不同载体制成的固体分散体均能增加他克莫司体外溶出度,通过比较优选出HPMCE3为最佳载体。物相鉴定表明,他克莫司大部分以无定型状态分散于HPMCE3中。结论:制备他克莫司-HPMCE3固体分散体可以明显提高其体外溶出度,且制备方法简单可行。     

布格呋喃固体分散体的体外研究

布格呋喃(buagafuran,AF-5)是以( )香芹酮为起始原料通过立体选择性合成的沉香呋喃类化合物[1].它具有显著的抗焦虑作用,毒副作用低,市场前景广阔.布格呋喃为油状液体,脂溶性强,不溶于水.用植物油稀释进行小鼠灌胃,抗焦虑活性与空白组比较无统计学意义,不能较好地发挥药效.室温放置易发生降解,化学稳定性差.这些缺     

尼群地平固体分散体的研制

为了提高难溶性药物尼群地平的溶出度,制备了其固体分散体,考察其体外溶出度并与原料药作对照,筛选出较佳的处方。     

Formulation of immediate release pellets containing famotidine solid dispersions

Famotidine (FM) is a potent H2-receptor antagonist used for the treatment of peptic ulcer. It has a low and variable bioavailability which is attributed to its low water solubility. In this study, the dissolution of the drug was enhanced by a preparation of solid dispersion using two hydrophilic carriers, namely Gelucire 50/13 and Pluronic F-127. The prepared solid dispersions were characterized by differential scanning calorimetry (DSC), which indicated that there were no signs of interaction of the drug with the carriers used in the case of solid dispersions containing higher polymeric contents (1:3 and 1:5). FM solid dispersions in the matrices of Gelucire 50/13 and Pluronic F-127 (1:3) were used to prepare pellets. The scanning electron microscope (SEM) images of pellets showed that the pellets have spherical shape and their size depends on the carrier used. The dissolution of the drug from either solid dispersion or pellets was performed. The dissolution study depicted that, the presence of the drug in solid dispersion enhanced its dissolution in comparison with the drug itself. Also, the drug release from the manufactured pellets was found to be improved in the case of solid dispersions (drug:carrier 1:3). A complete drug release occurred after 30 min from pellets containing solid dispersions, while only about 30% of the loaded FM was released from pellets containing untreated drug after 2 h.     

依托泊苷固体分散体的制备及体外研究

目的 制备依托泊苷固体分散体，改善依托泊苷的溶出度。方法 应用聚乙烯吡咯烷酮（PVPK30）和聚乙二醇（PEG6000）为载体，以溶剂法制备固体分散体。采用正交实验设计考察制备固体分散体的最佳工艺条件，并对所得样品进行体外溶出度研究，以X线衍射、DSC-量热分析进行物相鉴定。结果 依托泊苷在载体PVPK30和PEG6000中结晶消失。药物的溶出速度随载体比例增加而增加。结论 采用PVPK30和PEG6000所制依托泊苷固体分散体能显著提高药物的体外溶出度，药物以无定形状态或分子态存在于载体中。     

索拉非尼固体分散体的制备及性质研究

目的制备索拉非尼(sorafenib,SFN)/介孔硅的固体分散体,并进行体内外性质研究。方法利用溶剂挥发法制备固体分散体,以溶出度为指标筛选药物和介孔硅比例;采用差示扫描量热法(DSC)和粉末X射线衍射(XRD)技术,考察药物存在状态及物理稳定性;通过电镜观察样品形貌;以大鼠为实验动物,以自制SFN粉末为对照,对固体分散体进行体内药动学研究。结果原料药为结晶态,溶出度<10%;随着介孔硅的比例增大,固体分散体的溶出度增加,当SFN与介孔硅的比例为1∶5时,SFN以非晶态存在,溶出度>90%,在6个月的加速实验中,药物存在状态和溶出度未见明显改变。固体分散体组的cmax是SFN粉末组的1.8倍,相对生物利用度为175%。结论 SFN/介孔硅固体分散体物理稳定性良好,能提高SFN的溶出度,改善其口服吸收效果。     

Development of novel ibuprofen-loaded solid dispersion with improved bioavailability using aqueous solution

To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability, various ibuprofen-loaded solid dispersions were prepared with water, HPMC and poloxamer. The effect of HPMC and poloxamer on aqueous solubility of ibuprofen was investigated. The dissolution and bioavailability of solid dispersion in rats were then evaluated compared to ibuprofen powder. When the amount of carrier increased with a decreased in HPMC/poloxamer ratio, the aqueous solubility of ibuprofen was elevated. The solid dispersion composed of ibuprofen/HPMC/poloxamer at the weight ratio of 10:3:2 improved the drug solubility approximately 4 fold. It gave significantly higher initial plasma concentration, AUC and Cmax of drug than did ibuprofen powder in rats. The solid dispersion improved the bioavailability of drug about 4-fold compared to ibuprofen powder. Thus, this ibuprofen-loaded solid dispersion with water, HPMC and poloxamer was a more effective oral dosage form for improving the bioavailability of poor water-soluble ibuprofen.     

Preparation and characterization of solid dispersions of Quercetin with PEG4000

Objective To enhance the solubility,quicken the speed of digesting and absorption,and increase the bioavailability of quercetin(3,3',4',5,7-pentahydroxyflavone).Methods A series of Quercetin-PEG4000 solid dispersions were prepared by fusion method.The configuration and property of solid dispersion were characterized by solubility tests,dissolution tests,FTIR spectra,differential scanning calorimetry(DSC)and microphotograph.Results 1.According to solubility tests the the mass ratio of quercetin to PEG4000 affected strongly on the solubility of solid dispersions,on the whole,the relation of the solubility of solid dispersions to the mass ratio presented linear relationship.The preparation temperature had little effect on the solubility of solid dispersions.The surface-active agent,polysorbate80 increased strongly the solubility of solid dispersions.2.According to the dissolution tests,the mass ratio of quercetin to PEG4000 affected strongly on the dissolution of solid dispersions,the preparation temperature had little effect on the dissolution of solid dispersions.The surface-active agent,polysorbate80 increased strongly the dissolution of solid dispersions,and after addition polysorbate80,the dissolution of solid dispersions was two times of the dissolution of solid dispersions without polysorbate80.3.According to the DSC results,except that a little of quercetin molecular existed as crystalline state in the solid dispersion with the mass ratio was qu:PEG=1:2,quercetin existed as amorphous phase in other mass ratio solid dispersion.4.According to the FTIR spectra and microphotograph results,the relation of quercetin and PEG4000 was mainly physical mixing in quercetin-PEG4000 solid dispersion.Quercetin was just like solute in solution,and PEG4000 was just like solvent in solution.The force between quercetin and PEG4000 was mainly hydrogen bonding,so the biological activity of quercetin would not be influenced greatly after the formation solid dispersion.Conclusions These results suggest that quercetin existed mainly as amorphous phase in solid dispersion;the solubility and the dissolution in water were increased obviously after formation the solid dispersion.     

三元固体分散体提高利多卡因溶解度研究（英文）

使用熔融法制备利多卡因-泊洛沙姆固体分散体以提高利多卡因的溶解度及溶出度。以利多卡因(LIC)作为模型药物,分别使用泊洛沙姆188 (P188)和泊洛沙姆407 (P407)作为单一及混合载体,制备三元及二元固体分散体并进行比较。使用DSC、XRD、SEM及FTIR进行一系列表征,通过溶出度试验研究固体分散体的溶出特性,药物以晶体形式存在于载体中,药物溶出度及溶解度结果较原料药均有明显提高。相溶解度研究显示出药物与载体呈AL型曲线,有分子相互作用的存在。此外,还考察了固体分散体在不同相对湿度下的长期稳定性,稳定性测试结果表明三元及二元利多卡因-泊洛沙姆固体分散体在不同湿度下,6个月内保持稳定。研究结果表明,混合泊洛沙姆三元固体分散体可以显著提高难溶性利多卡因的溶出度和溶解度。     

Preparation, dissolution and characterization of albendazole solid dispersions

In this study, solid dispersion systems of the sparingly water soluble drug, albendazole (ABZ), were mixed with varying concentrations of polyvinylpyrrolidone (PVP K 12) in an attempt to improve the solubility and dissolution rate of ABZ. Physical characteristics were investigated by Powder X-ray diffraction. As expected, the albendazole dissolution rate, expressed as the dissolution efficiency, and also the solubility coefficient were increased when albendazole was mixed with PVP. An increase in the concentration of the polymer in the solid dispersion produced an increase in both parameters. The powder X-ray diffraction patterns showed that the solid dispersion presented an amorphous form of albendazole in this coprecipitate system.     

非布司他临床应用及不良反应

非布司他是一种新型选择性黄嘌呤氧化酶抑制剂,主要用于具有痛风症状的高尿酸血症患者的治疗。非布司他的推荐起始剂量为40 mg,1次/d。目前尚无充分依据证实非布司他降尿酸的临床疗效优于别嘌醇,但有研究提示在合并糖尿病或年龄≥65岁的痛风患者中,非布司他80 mg/d组的治疗效果更佳。非布司他常见的不良反应包括肝功能异常、腹泻、头痛、恶心及皮疹等,心血管系统不良反应与别嘌醇比较尚未发现差异有统计学意义。