阿魏酸钠滴丸的制备及溶出度测定

目的：通过固体分散技术制备滴丸，以提高阿魏酸钠的溶出度。方法：以聚乙二醇（PEG）6000、泊洛沙姆188为载体基质制备滴丸，HPLC法测定含量，转篮法考察溶出度。结果：滴丸中PEG6000／药物比值越大．阿魏酸钠溶出越快；所制得滴丸外观圆整，质地均匀；分别以0．1mol／L盐酸溶液、水、pH6,8磷酸盐缓冲液为溶出介质，阿魏酸钠滴丸均较市售片显著增加溶出度。结论：阿魏酸钠滴丸具有良好的速释效果。     

不同基质的吴藿降压滴丸中吴茱萸碱体外溶出研究

目的:比较不同基质的吴藿降压滴丸中吴茱萸碱体外溶出差异。方法:分别以泊洛沙姆-188、聚乙二醇(PEG)4000、PEG6000为基质,制备吴藿降压滴丸;测定各滴丸中吴茱萸碱的体外溶出度,绘制溶出曲线,求出累积溶出参数,并进行分析。结果:以泊洛沙姆-188、PEG4000、PEG6000为基质制备的滴丸中吴茱萸碱的溶出度分别为99.1%、95.2%、93.6%。以PEG4000、PEG6000为基质制备的滴丸中吴茱萸碱溶出速度较泊洛沙姆-188快,但吴茱萸碱溶出量较后者低。结论:泊洛沙姆-188、PEG类均为非离子型表面活性剂,对吴茱萸碱的溶出起增溶作用,泊洛沙姆-188增溶效果强于PEG类。     

玳玳果黄酮滴丸的溶出度及速释机制

目的:评价玳玳果黄酮滴丸的溶出度并初步探讨其速释机制。方法:在多种pH值溶出介质中采用多条溶出曲线评价玳玳果黄酮滴丸的体外溶出度,以柚皮苷为指标成分,运用HPLC法考察玳玳果黄酮滴丸在不同时间的累积溶出百分数,并通过差示扫描热分析研究滴丸的速释机制。结果:4种释放介质中柚皮苷在2.12～53.00mg.L-1范围内线性关系良好,玳玳果黄酮滴丸中柚皮苷在20 min时累积溶出度可达85%。差示扫描量热分析结果显示,玳玳果黄酮在PEG4000-PEG6000中形成了某种形式的固体分散体。结论:玳玳果黄酮滴丸具有良好的溶出度,玳玳果黄酮有效部位在滴丸内形成了良好的固体分散体,使药物在基质中的分散度增加而达到速释。     

(噁)丙嗪固体分散体的制备

目的:制备噁丙嗪固体分散体.方法:以聚乙二醇(PEG 6000)为载体,采用熔融法制备噁丙嗪固体分散体,桨法测定体外溶出度,X-射线衍射法分析结构状态.结果:噁丙嗪-PEG 6000固体分散体是一种简单低共熔混合物,噁丙嗪以超细结晶状态分散在PEG载体中.1:5,1:7,1:9,1:11比例固体分散体的标示含量均在98%～106%范围.与原料药及物理混合物相比,固体分散体的溶出速度和程度均显著增加(P＜0.01);且随着载体比例的逐渐增大,固体分散体的药物溶出加快.结论:以PEG 6000为载体制备的噁丙嗪固体分散体体外溶出迅速,可用于制备速效、高效的噁丙嗪口服制剂.     

尼莫地平固体分散物的制备及其片剂溶出度的研究

目的：提高难溶性药物尼莫地平的溶出速率。方法：选用PVP－k30和PEG6000为载体制备了不同晶型尼莫地平固体分散物和机械混合物，比较了它们片剂体外的溶出速率。结果：尼莫地平固体分散物的片剂溶出度高于机械混合物的，低熔点机械混合物片剂溶出度高于高熔点的，不同晶型尼莫地平PEG6000固体分散物片剂体外的溶出速率无显著性差异，低熔点尼莫地平PVK－k30固体分散物的片剂的90min累积溶出量比高熔点的高。结论：不同晶型尼莫地平制备成PVP-k30和PEG6000固体分散物都可以提高其片剂体外的溶出度。     

共研磨法改善枸橼酸莫沙必利的体外溶出度

目的 改善枸橼酸莫沙必利的体外溶出度.方法 采用共研磨法,分别制备枸橼酸莫沙必利与低取代羟丙基纤维素(L-HPC)、羟丙甲纤维素(HPMC)、聚维酮(PVP)或聚乙二醇6000(PEG 6000)(1∶2)的共研磨物,测定原料药、物理混合物和共研磨物的溶出度;运用X射线衍射法和差示扫描量热法鉴别药物在共研磨物中的存在状态,并考察其稳定性.结果 枸橼酸莫沙必利与L-HPC和HPMC共研磨物的溶出度较原料药的显著提高,且稳定性较好.结论 共研磨法能够改善枸橼酸莫沙必利的体外溶出度.     

索法酮固体分散体的制备及体外溶出特性

目的:制备索法酮固体分散体并考查其体外溶出特性.方法:以PEG 2000、PEG 4000和PEG 6000为载体,采用熔融法制备固体分散体,与物理混合物比较体外溶出度.结果:PEG 4000和PEG 6000制得的固体分散体的体外溶出度高于PEG 2000,均高于物理混合物.载体比例越大,体外溶出越快.结论:以PEG为载体,采用熔融法可制得体外溶出较快的索法酮固体分散体.     

以聚醚为基质研制耳用滴丸

采用水溶性非离子型表面活性剂聚醚作基质制备吡哌酸耳用滴丸。与 PEG 制备的滴丸比较,两种滴丸的溶出度和透皮吸收率有显著差异。聚醚所制滴丸溶出及吸收均较慢,但制备工艺简单,兔口服给药的药动学参数两种滴丸未见差异。     

卡维地洛固体分散体的初步研制

目的:制备卡维地洛固体分散体并考察其体外溶出度。方法:以聚乙二醇(PEG)、聚乙烯吡咯烷酮(PVP)的混合物(2∶1、1∶2)为载体,采用溶剂熔融法和共沉淀法制备载体与药物不同比例的固体分散体并比较其体外溶出度。结果:药物溶出度随载体比例增加而增加;载体与药物比例越小,固体分散体与药物原料粉之间溶出度差异越显著;PEG∶PVP(1∶2)所制分散体体外溶出行为较优,以3、10、30、60min时溶出百分率进行比较,固体分散体是药物原料粉的3～8倍。结论:所制卡维地洛固体分散体能增加药物体外溶出度。     

共研磨法提高兰索拉唑的溶出度

采用共研磨法分别制备兰索拉唑与β-环糊精(β-CD)、低取代羟丙纤维素(L-HPC)、羟丙甲纤维素(HPMC)、聚乙烯吡咯烷酮(PVP)、交联聚维酮(PVPP)、聚乙二醇(PEG)6000或壳聚糖(1:1)的共研磨物,测定了原药、物理混合物和共研磨物的溶出度,并用差示扫描量热法和X-射线衍射法鉴别药物在共研磨物中的存在状态.测定了兰索拉唑原药、物理混合物和共研磨物于室温放置6个月后的含量和溶出度,考察共研磨样品的稳定性.结果表明,兰索拉唑与β-CD、L-HPC、HPMC、PVP和壳聚糖的共研磨物的溶出度较兰索拉唑原药有显著提高,且稳定性较好.     

茴三硫-聚乙二醇类固体分散体的研究

目的制备茴三硫固体分散体,提高其溶解度和溶出速率。方法以不同分子量不同比例的聚乙二醇为载体,以熔融法制备固体分散体,并进行体外溶出度研究和DSC扫描。结果茴三硫与聚乙二醇可形成低共熔物,并使溶出度大大增加,载体比例越大,药物溶出愈快。结论本试验所制茴三硫固体分散体能加速体外溶出,体外溶出与载体分子量无关,但与固体分散体载体比例有关。     

茴三硫-聚乙二醇类固体分散体的研究

目的 制备茴三硫固体分散体，提高其溶解度和溶出速率.方法 以不同分子量不同比例的聚乙二醇为载体，以熔融法制备固体分散体，并进行体外溶出度研究和DSC扫描.结果 茴三硫与聚乙二醇可形成低共熔物，并使溶出度大大增加，载体比例越大，药物溶出愈快.结论 本试验所制茴三硫固体分散体能加速体外溶出，体外溶出与载体分子量无关，但与固体分散体载体比例有关。     

Physical Stability of Solid Dispersions Containing Triamterene or Temazepam in Polyethylene Glycols

The effect of storage on the physical stability of solid dispersions of triamterene or temazepam in polyethylene glycols was studied using differential scanning calorimetry (DSC), particle-size analysis and dissolution methods. The enthalpies of fusion of the carriers, without included drug and previously fused and crystallized, increased on storage. Analysis of similarly treated solid dispersions, containing either 10% temazepam or 10% triamterene, showed that each drug influenced the morphology of the polyethylene glycol (PEG). The enthalpies and melting points of the solidus components of the dispersions' carriers were initially reduced after preparation, but on storage these increased. The particle sizes of the drugs dispersed in the PEGs increased on storage. The changes in dissolution after storage of triamterene or temazepam dispersions were smaller for dispersions in PEG 1500 than for dispersions in PEGs of higher molecular weight (PEG 2000, PEG 4000 or PEG 6000) in which the reduction in dissolution was particularly marked during the first month of storage. The rank order of changes in dissolution were PEG 1500 ? PEG 2000 < PEG 4000 ～ PEG 6000.     

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.     

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.     

Processing factors in development of solid solution formulation of itraconazole for enhancement of drug dissolution and bioavailability

This study investigated solid solutions of itraconazole, a water insoluble antifungal, for improved dissolution and improved bioavailability. Influence of processing factors on drug and carrier properties in solid solution and subsequently on drug dissolution behavior was also studied. An optimized solid solution formulation was compared with marketed product in healthy human subjects under fasted and fed conditions for bioequivalency. Polyethylene glycol (PEG) and drug were made into a solid solution at 120 degrees C. The cooled, solid solution was then ground into granules of different sizes. Solid solutions of lower drug concentration dissolved at a faster rate, and drug dissolution improved considerably with increasing molecular weight of PEG. Initial treatment of itraconazole with the wetting agent/cosolvent glycerol prior to making itraconazole into a solid solution improved drug dissolution, and also reduced the PEG amount required to dissolve drug to form solid solution. Addition of a polymer such as HPMC to the solid solution eliminated precipitation of drug following dissolution. As the granule size of the solid solution was reduced, precipitation of drug during dissolution became prominent. Equivalence of two formulations could not be shown for pharmacokinetic parameters C(max) and AUC, under both fasting and fed conditions.     

The properties of solid dispersions of indomethacin or phenylbutazone in polyethylene glycol

The effects of molecular weight of polyethylene glyeols (PEGs) on the dissolution rates and crystallinity of its solid dispersions with indoniethacin and phenylbutazone have been examined. The dissolution rates of both solid-dispersed drugs decreased as the molecular weight of PEG increased. The indoniethacin dissolution profiles were essentially linear using constant surface area disc methodology and a limiting dissolution rate of about 10.6 mg · min⁻¹ was observed. The phenylbutazone dissolution profiles were. however, generally linear-curvic usually giving lower release rates than the comparative indomethacin weight fractions. A limiting dissolution rate for the linear portions of the profiles was about 1.8 mg · min⁻¹. Infra-red spectra indicated that the differences between the two drugs could partly be explained on the basis of PEG crystallinity. Generally bands in the ranges 1100–1130 and 1200–1400 cm⁻¹ were poorly differentiated in indomethacin dispersions (PEG 1500, PEG 4000 and PEG 6000) but were better differentiated in phenylbutazone dispersions (PEG 4000, PEG 6000 and PEG 20,000). A greater proportion of amorphousness within the PEG moiety was predicted in indomethacin dispersions by the appearance of a new weak band at 1326 cm⁻¹ and by a decrease in intensity of the band at 845 cm⁻¹ at the expense of the peak at 960 cm⁻¹. The evidence was supported by differential scanning calorimetry. The heats of fusion were 44.7, 46.4, 47.2 and 39.5 cal · g⁻¹ for PEG 1500, PEG 4000, PEG 6000 and PEG 20.000 respectively. Heats of fusion for indomethacin dispersions (2, 5 and 10% drug) were generally lower than for the corresponding values for phenylbutazone dispersions-with the exception of PEG 20,000 dispersions. For example, values were obtained of 30.6 and 37.9 cal · g⁻¹ for PEG 1500 dispersions containing 10% indomethacin and phenylbutazone, respectively.     

Development of PVP/PEG mixtures as appropriate carriers for the preparation of drug solid dispersions by melt mixing technique and optimization of dissolution using artificial neural networks

The effect of plasticizer’s (PEG) molecular weight (MW) on PVP based solid dispersions (SDs), prepared by melt mixing, was evaluated in the present study using Tibolone as a poorly water soluble model drug. PEGs with MW of 400, 600, and 2000 g/mol were tested, and the effect of drug content, time and temperature of melt mixing on the physical state of Tibolone, and the dissolution characteristics from SDs was investigated. PVP blends with PEG400 and PEG600 were completely miscible, while blends were heterogeneous. Furthermore, a single T_g recorded in all samples, indicating that Tibolone was dispersed in a molecular lever (or in the form of nanodispersions), varied with varying PEG’s molecular weight, melt mixing temperature, and drug content, while FTIR analysis indicated significant interactions between Tibolone and PVP/PEG matrices. All prepared solid dispersion showed long-term physical stability (18 months in room temperature). The extent of interaction between mixture components was verified using Fox and Gordon–Taylor equations. Artificial neural networks, used to correlate the studied factors with selected dissolution characteristics, showed good prediction ability.     

Factors affecting the formation of eutectic solid dispersions and their dissolution behavior

The objective of this work was to obtain a fundamental understanding of the factors, specifically the properties of poorly water-soluble drugs and water-soluble carriers, which influence predominantly, the formation of eutectic or monotectic crystalline solid dispersion and their dissolution behavior. A theoretical model was applied on five poorly water-soluble drugs (fenofibrate, flurbiprofen, griseofulvin, naproxen, and ibuprofen) having diverse physicochemical properties and water-soluble carrier (polyethylene glycol (PEG) 8000) for the evaluation of these factors. Of these, two drugs, fenofibrate and flurbiprofen, and PEG of different molecular weights (3350, 8000, and 20000), were chosen as model drugs and carriers for further investigation. Experimental phase diagrams were constructed and dissolution testing was performed to assess the performance of the systems. The theoretical model predicted the formation of eutectic or monotectic solid dispersions of fenofibrate, griseofulvin, ibuprofen, and naproxen with PEG, holding the contribution of specific intermolecular interactions between compound and carrier to zero. In the case of the flurbiprofen-PEG eutectic system, intermolecular interactions between drug and polymer needed to be taken into consideration to predict the experimental phase diagram. The results of the current work suggest that the thermodynamic function of melting point and heat of fusion (as a measure of crystal energy of drug) plays a significant role in the formation of a eutectic system. Lipophilicity of the compound (as represented by cLog P) was also demonstrated to have an effect. Specific interactions between drug and carrier play a significant role in influencing the eutectic composition. Molar volume of the drug did not seem to have an impact on eutectic formation. The polymer molecular weight appeared to have an impact on the eutectic composition for flurbiprofen, which exhibits specific interactions with PEG, whereas no such impact of polymer molecular weight on eutectic composition was observed for fenofibrate, which does not exhibit specific interactions with PEG. The impact of polymer molecular weight on dissolution of systems where specific drug-polymer interactions are exhibited was also observed. The current work provides valuable insight into factors affecting formation and dissolution of eutectic systems, which can facilitate the rational selection of suitable water-soluble carriers.     

PEG 6 000固体分散体系对难溶性药物水飞蓟素的增溶作用与晶格变化的关系

目的研究PEG 6 000固体分散体系对难溶性药物增溶的相关晶格变化规律。方法用熔融法制备水飞蓟素的PEG 6 000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,以X-射线粉末多晶衍射结合相应的衍射峰处理软件系统分析PEG 6 000及药物的晶格参数的变化,经傅立叶变换红外光谱(FT-IR)验证PEG 6 000与药物之间的相互作用。结果与原药比较,固体分散体中药物的释放速率明显增大,PEG 6 000固体分散体系对难溶性药物水飞蓟素具有显著的增溶作用。X-射线多晶衍射分析表明,PEG 6 000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发生了规律性变化,药物与载体间无相互作用。结论PEG 6 000固体分散体系的增溶作用与载体材料和药物的晶格参数的改变密切相关。