硝苯地平固体分散体制备工艺的研究

目的利用固体分散技术将硝苯地平制成固体分散体,提高其体外溶出速率。方法分别以聚乙二醇6000(PEG6000)、聚乙二醇4000(PEG4000)、聚乙烯吡咯烷酮K30(PVPK30)、泊洛沙姆188(Pluronic F68)等为载体,用熔融法、溶剂法、溶剂-熔融法和喷雾干燥法制备硝苯地平固体分散体。采用差热分析法(DTA)分析药物在固体分散体中的存在状态,并进行体外溶出度试验。结果各种固体分散体均能加快药物的溶出速率,并且随着载体在固体分散体中的比例增大,溶出速率增大。DTA分析显示硝苯地平在PVPK30的固体分散体中以微细结晶存在。结论将硝苯地平制成固体分散体能显著提高硝苯地平的体外溶出速率。     

环孢素固体分散体的制备及溶出研究

目的: 提高难溶性药物环孢素(CsA)的溶出速率.方法: 选择聚乙二醇(PEG4000)和聚乙烯吡咯烷酮(PVPK30)两种载体,分别以溶剂熔融法和溶剂法制备CsA固体分散体;建立HPLC法检测固体分散体的体外溶出度,并考察不同载体、不同比例及溶出介质、桨法转速对CsA溶出速率的影响.对溶出度结果用Weibull分布模型进行拟合,计算体外溶出参数T50和Td,并进行方差分析.结果: 使用HPLC法测定CsA的体外溶出量准确、稳定、可靠、载体无干扰.制备成的固体分散体能显著提高CsA的体外溶出速率,PVPK30载体的固体分散体的溶出速率明显快于PEG4000载体的固体分散体.溶出介质对药物溶出没有明显影响.结论: CsA: PVPK30为1: 6的固体分散体具有良好的体外速释作用.     

固体分散技术提高黄芩提取物溶出度的研究

目的：通过制备固体分散体，提高黄芩提取物的溶出度。方法：采用熔融法和溶剂法，制备聚乙二醇4000（PEG4000），聚乙二醇6000（PEG6000），聚乙烯吡咯烷酮K30（PVPK30）3种载体材料及不同比例条件下的固体分散体。通过比较原药材、固体分散体、机械混合物的溶出性能，从而确定制备的最佳方法和最佳比例。结果：不同载体不同比例的固体分散体均能提高药物的溶出度，且载体比例越大，药物的溶出越快，3种载体的增溶效果依次为PVPK30〉PEG4000〉PEG6000。结论：以PVP为载体，采用溶剂法所制备的药物/载体比例为1：6的固体分散体能显著提高黄芩提取物的溶出速率。     

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。     

水溶性呋喃西林固体分散体配方及工艺研究

目的 利用固体分散技术制备水溶性呋喃西林固体分散体,增加其溶解度.方法 选择聚乙二醇6000(PEG)为载体, 采用熔融法、溶剂-熔融法,按药物与载体1:3、1:6、1:9的比例分别制成不同的呋喃西林固体分散体,将呋喃西林原药与呋喃西林固体分散体进行体外溶出度试验和溶解度试验.结果 呋喃西林固体分散体的体外溶出度和溶解度与呋喃西林原药相比显著增大.结论 选择呋喃西林与聚乙二醇(PEG)-6000(1:6)及溶剂-熔融法作为水溶性呋喃西林固体分散体的配方及工艺,可使呋喃西林的溶解度提高.     

洛伐他汀固体分散体的制备及体外溶出特性比较

目的：利用固体分散技术制备洛伐他汀固体分散体，增加其溶出速率。方法：以不同比例的聚乙烯吡咯烷酮（PVPk-30）、聚乙二醇6000（PEG6000）为载体，采用溶剂法和熔融法制成洛伐他汀固体分散体，测定其溶出速率，并采用差示扫描量热（DSC）法、显微照相技术鉴别药物在固体分散体中的存在状态。结果：两种固体分散体均能提高洛伐他汀溶出速率，在药物载体比例大于1：5时效果较好；洛伐他汀固体分散体中晶型消失，分散在载体中。载体为PVPK30所制固体分散体的溶出速率总体优于载体PEG6000。结论：固体分散体能加速洛伐他汀溶出速率。     

冬凌草甲素固体分散体的制备及溶解性能研究

目的 采用固体分散技术,提高冬凌草甲素的体外溶解性能。方法 分别以聚乙二醇6000(PEG6000)、聚乙烯吡咯烷酮K30(PVPK30)为载体,制备冬凌草甲素固体分散体。采用紫外分光光度法进行含量测定,差示热分析法鉴别药物在载体中的存在状态,并进行溶解度、体外溶出速率实验。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,冬凌草甲素在载体中以高度分散状态存在。结论 以 PVPK30为载体制备的冬凌草甲素固体分散体体外溶解度和溶出速率明显提高。     

固体分散体提高银杏叶片溶出度的研究

目的:通过制备固体分散体提高银杏叶片中银杏叶提取物(EGb)的溶出度.方法:采用溶剂熔融法、喷雾干燥法制备聚乙二醇6000(PEG 6000)和聚乙烯吡咯烷酮K17(PVPK17)2种载体材料、不同比例的固体分散体,并比较固体分散体、物理混合物和EGb、市售普通片的溶出特性.对EGb-PEG 6000固体分散体进行差示热扫描(DSC)分析.结果:溶剂熔融法和喷雾干燥法可制备不同比例的PEG 6000,PVPK17的EGb固体分散体,EGb-PEG 6000(1:2)固体分散体片溶出度增加明显,且增溶效果优干EGb-PVPK17固体分散体.结论:EGb-PEG 6000(1:2)固体分散体能有效提高银杏叶片的溶出度.     

卡维地洛固体分散体的制备及其体外溶出度的测定

目的 :制备卡维地洛固体分散体 ,提高其溶解度和溶速率。方法 :以聚乙烯吡咯烷酮 (PVP)、聚乙二醇 -6000(PEG -6000)为载体 ,以溶剂法和熔融法制备固体分散体 ,并进行体外溶出度研究。结果 :载体比例越大 ,药物溶出愈快 ;载体比例愈小 ,差异愈显著。载体为PVP所制固体分散体的体外溶出行为总体优于载体为PEG -6000的固体分散体。结论 :本试验所制卡维地洛固体分散体能加速体外溶出 ,提高生物利用度 ,可用于制备高效制剂     

冬凌草甲素固体分散体的制备及溶解性能研究

目的采用固体分散技术,提高冬凌草甲素的体外溶解性能。方法分别以聚乙二醇6000（PEG6000）、聚乙烯吡咯烷酮K30（PVPK30）为载体,制备冬凌草甲素固体分散体。采用紫外分光光度法进行含量测定,差示热分析法鉴别药物在载体中的存在状态,并进行溶解度、体外溶出速率实验。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,冬凌草甲素在载体中以高度分散状态存在。结论以PVPK30为载体制备的冬凌草甲素固体分散体体外溶解度和溶出速率明显提高。     

Characteristics of rofecoxib-polyethylene glycol 4000 solid dispersions and tablets based on solid dispersions

The aim of this work was to report the properties of rofecoxib-PEG 4000 solid dispersions and tablets prepared using rofecoxib solid dispersions. Rofecoxib is a poorly water soluble nonsteroidal anti-inflammatory drug with a poor dissolution profile. This work investigated the possibility of developing rofecoxib tablets, allowing fast, reproducible, and complete rofecoxib dissolution, by using rofecoxib solid dispersion in polyethylene glycol (PEG) 4000. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the solid state of solid dispersions. The effect of PEG 4000 concentration on the dissolution rate of rofecoxib from its solid dispersions was investigated. The dissolution rate of rofecoxib from its solid dispersions increased with an increasing amount of PEG 4000. The extent of dissolution rate enhancement was estimated by calculating the mean dissolution time (MDT) values. The MDT of rofecoxib decreased significantly after preparing its solid dispersions with PEG 4000. The FTIR spectroscopic studies showed the stability of rofecoxib and absence of well-defined rofecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of rofecoxib in solid dispersions of rofecoxib with PEG 4000. SEM pictures showed the formation of effective solid dispersions of rofecoxib with PEG 4000 since well-defined change in the surface nature of rofecoxib and solid dispersions were observed. Solid dispersions formulation with highest drug dissolution rate (rofecoxib: PEG 4000 1:10 ratio) was used for the preparation of solid dispersion-based rofecoxib tablets by the direct compression method. Solid dispersion-based rofecoxib tablets obtained by direct compression, with a hardness of 8.1 Kp exhibited rapid drug dissolution and produced quick anti-inflammatory activity when compared to conventional tablets containing pure rofecoxib at the same drug dosage. This indicated that the improved dissolution rate and quick anti-inflammatory activity of rofecoxib can be obtained from its solid dispersion-based oral tablets.     

Characteristics of Rofecoxib-Polyethylene Glycol 4000 Solid Dispersions and Tablets Based on Solid Dispersions

The aim of this work was to report the properties of rofecoxib-PEG 4000 solid dispersions and tablets prepared using rofecoxib solid dispersions. Rofecoxib is a poorly water soluble nonsteroidal anti-inflammatory drug with a poor dissolution profile. This work investigated the possibility of developing rofecoxib tablets, allowing fast, reproducible, and complete rofecoxib dissolution, by using rofecoxib solid dispersion in polyethylene glycol (PEG) 4000. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the solid state of solid dispersions. The effect of PEG 4000 concentration on the dissolution rate of rofecoxib from its solid dispersions was investigated. The dissolution rate of rofecoxib from its solid dispersions increased with an increasing amount of PEG 4000. The extent of dissolution rate enhancement was estimated by calculating the mean dissolution time (MDT) values. The MDT of rofecoxib decreased significantly after preparing its solid dispersions with PEG 4000. The FTIR spectroscopic studies showed the stability of rofecoxib and absence of well-defined rofecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of rofecoxib in solid dispersions of rofecoxib with PEG 4000. SEM pictures showed the formation of effective solid dispersions of rofecoxib with PEG 4000 since well-defined change in the surface nature of rofecoxib and solid dispersions were observed. Solid dispersions formulation with highest drug dissolution rate (rofecoxib: PEG 4000 1:10 ratio) was used for the preparation of solid dispersion–based rofecoxib tablets by the direct compression method. Solid dispersion–based rofecoxib tablets obtained by direct compression, with a hardness of 8.1 Kp exhibited rapid drug dissolution and produced quick anti-inflammatory activity when compared to conventional tablets containing pure rofecoxib at the same drug dosage. This indicated that the improved dissolution rate and quick anti-inflammatory activity of rofecoxib can be obtained from its solid dispersion–based oral tablets.     

缬沙坦固体分散体的制备及体外溶出度研究

目的采用冷冻干燥法制备缬沙坦（Valsartan）速释固体分散体（SD）来提高其体外溶出度。方法分别以羟丙甲基纤维素（HPMC）、聚乙二醇6000（PEG6000）、聚乙烯吡咯烷酮k30（PVPk30）为载体,十二烷基硫酸钠（SDS）为表面活性剂来制备不同比例的缬沙坦固体分散体,通过测定体外溶出度,来选择最优辅料及比例,结果当以PEG6000载体,SDS为表面活性剂时,且药物：PEG6000：SDS=1：5：1％时药物呈现了很好的水溶性。结论在5min时即可溶出90％以上,很大程度上提高了缬沙坦的体外溶出度。     

Improvement of the dissolution kinetics of SR 33557 by means of solid dispersions containing PEG 6000

Solid dispersions of SR 33557 in preparations containing from 30 to 80% w/w polyethylene glycol 6000 (PEG 6000) were prepared by the fusion method. The solubility of the drug substance either alone or in solid dispersions was determined in pH 1.2 and 4.5 media (extraction fluid NFXII, without enzyme). A large increase in the solubility was noted from the 80% w/w PEG preparation. A wettability study performed by measuring the contact angle on tablets of either drug substance or PEG 6000, or solid dispersions, revealed a minimal contact angle for the 80% w/w PEG 6000 solid dispersion (eutectic composition of SR 33557/PEG 6000 phase diagram). Dissolution kinetic analysis performed at pH 1.2 on all solid dispersions, on the physical mixtures containing 70 and 80% w/w PEG 6000, and on SR 33557 alone, showed a maximum release rate (100%) for the solid dispersions containing 70 and 80% w/w PEG 6000. The dissolution rate of the physical mixtures was faster than that of the drug substance alone but remained, however, lower than that of the solid dispersions, at the same composition. It was also observed that the dissolution rate, at pH 1.2 and 4.5, of the 70% w/w PEG 6000 solid dispersion was practically pH independent, which was not the case for the drug substance alone. The latter solid dispersion showed a slowing down of the dissolution kinetics after 3 months storage at 50°C whereas no change in the dissolution rate was observed following storage for 12 months at 25°C.     

水飞蓟素-聚乙二醇6000固体分散体系的制备及其特征考察

目的制备水飞蓟素固体分散体，加快药物的溶出，并进行特征考察。方法以聚乙二醇6000(PEG6000)为材料，采用熔融法将难溶性药物水飞蓟素制成固体分散体，通过体外释药试验考察固体分散技术对水飞蓟素的增溶作用，并以X-射线粉末衍射、傅立叶变换红外光谱(FT-IR)考察水飞蓟素固体分散体的特性。结果与原药比较，固体分散体中药物的释放速率明显增大，PEG6000固体分散体系能显著加快水飞蓟素的溶出。X-射线粉末衍射分析表明，PEG6000及药物在固体分散体中的晶格点阵面间距离、衍射峰位移及其相对强度等均发生了规律性变化，FT-IR分析表明PEG6000与药物间无相互作用。结论PEG6000固体分散体系的对难溶性药物溶出和扩散的加快，与载体材料和药物的晶格参数的改变密切相关。     

Physicochemical characterization and dissolution of norfloxacin/cyclodextrin inclusion compounds and PEG solid dispersions

Increase in the poor water solubility and dissolution rate of norfloxacin was studied. Two systems were used: solid dispersion with PEG 6000 prepared using the fusion method and inclusion complexes with cyclodextrins (β-cyclodextrin and HP-β-cyclodextrin) obtained by freeze-drying. IR spectrophotometry, X-ray diffractometry, and differential scanning calorimetry showed differences between norfloxacin/cyclodextrin complexes and their corresponding physical mixtures, but not between norfloxacin/PEG 6000 solid dispersions and their corresponding physical mixtures. The solubility and dissolution rate of norfloxacin were significantly increased with PEG solid dispersions and cyclodextrin complexes as well as with norfloxacin-CD physical mixtures. However, enhancement was not statistically different either among various cyclodextrin complexes, or between solid dispersions and cyclodextrin complexes.     

布渣叶总黄酮固体分散体的制备及体外溶出度测定

目的:采用固体分散体技术考察不同载体材料对布渣叶总黄酮提取物溶出度的影响.方法:选择不同种类的聚乙二醇、泊洛沙姆、聚乙烯吡咯烷酮为载体材料,与布渣叶总黄酮提取物按质量比1:4混合均匀,分别用熔融法和溶剂法制备固体分散体,以固体分散体中总黄酮、牡荆苷、异牡荆苷、水仙苷的90 min累积溶出度作为评价指标,比较不同载体制备的固体分散体的释药速率,并采用X射线衍射和红外光谱分析对其物相特征进行研究.结果:与布渣叶总黄酮提取物和物理混合物相比,以PEG和泊洛沙姆所制备的布渣叶提取物固体分散体中总黄酮、牡荆苷、异牡荆苷和水仙苷的体外溶出度与溶出速率均明显增加.其中以泊洛沙姆407为载体材料所制备的固体分散体中总黄酮体外溶出度最佳,90 min累积溶出度达到84%;以PEG 6000为载体材料所制备的固体分散体中牡荆苷、异牡荆苷、水仙苷体外溶出度最佳,90 min累积溶出度均达96%以上.结论:采用固体分散体技术,选择PEG 6000或泊洛沙姆407为载体制备布渣叶总黄酮提取物固体分散体,对提取物中脂溶性成分的溶出有明显改善作用.     

Enhanced release of solid dispersions of etodolac in polyethylene glycol

This work examines the release of etodolac from various molecular weight fractions of polyethylene glycol (PEG) solid dispersions. Solid dispersions of etodolac were prepared in different molar ratios of drug/carrier by using solvent and melting methods. The release rate of etodolac from the resulting complexes was determined from dissolution studies by use of USP dissolution apparatus 2 (paddle method). The physical state and drug:PEG interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction (XRD), infrared spectroscopy (IR) and differential scanning calorimetry (DSC). The dissolution rate of etodolac is increased in all of the solid dispersion systems compared to that of the pure drug and physical mixtures. The solid dispersion compound prepared in the molar ratio of 1:5 by the solvent method was found to have the fastest dissolution profile. The physical properties did not change after 9 months storage in normal conditions.     

浙贝提取物固体分散体的制备及溶出特性研究

目的：制备浙贝提取物固体分散体,考察其中贝母素甲及贝母素乙的溶出效果,从而确定制备的最佳方法和最佳比例。方法：选择聚乙二醇6000（PEG6000）与聚乙烯吡咯烷酮（PVP K30）两种载体材料,分别采用熔融法和溶剂法制备浙贝提取物固体分散体;通过比较提取物、固体分散体的溶出性能,确定最佳工艺。结果：使用HPLC-ELSD法测定贝母素甲及贝母素乙的溶出量,结果准确、可靠、稳定。制备成固体分散体能显著提高贝母素甲及贝母素乙的体外溶出速度;PEG6000作为载体的浙贝提取物固体分散体溶出速度快于PVP K30为载体的浙贝提取物固体分散体。结论：以PEG6000为载体,采用熔融法制备的药物/载体比例为1∶6的固体分散体能显著提高浙贝提取物中贝母素甲及贝母素乙的溶出速率。     

Influence of rapeseed phospholipids on ibuprofen dissolution from solid dispersions

The dissolution profiles of ibuprofen (IB) from solid dispersions prepared by the solvent evaporation method, containing the rapeseed lecithin ethanol soluble fraction (LESF) or rapeseed phosphatidylcholine (RPC) have been determined. The effect of incorporation of PEG 4,000 or PEG 8,000 in the solid dispersions on the controlled-release of IB was also investigated. Dissolution studies conducted in double-distilled water using the paddle dissolution apparatus showed that the initial dissolution rate (IDR) within the first 5 min and the maximum percent of dissolved IB of IB/LESF were double of those of IB/RPC (both in ratio 4:1 w/w). The low amounts of LESF markedly increased dissolution of IB. Increasing of LESF concentration from 0 to 10 and 20% in solid dispersions produced 60 and 100% improvement of IB maximum dissolution level respectively, to compare with that of IB alone. PEG 4,000 caused the slightly decreasing in IB dissolution rate, while PEG 8,000 markedly improved the dissolution of IB in examined conditions.