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。     

尼莫地平固体分散物的研究

尼莫地平临床上主要用于防治缺血性脑血管疾病．该药为难溶性药物，生物利用度低，本文采用了固体分散技术制备了尼莫地平两种固体分散物，其体外溶出速率１０分钟以内达８０％以上，较市售片有显著提高．两种固体分散物中，固体分散物Ⅰ为本实验室研制，固体分散物Ⅱ参照国内、外文献用ＰＶＰ为载体制备．两种固体分散物均能明显提高尼莫地平的体外溶出速率，但固体分散物Ⅱ易于老化，经相对湿度ＲＨ７５％４０℃贮藏３个月溶出速率明显下降，同样条件下，固体分散物Ⅰ则无明显变化．二种固体分散物Ｘ－射线衍射图谱表明尼莫地平以非晶体状态存在，而在ＲＨ７５％４０℃条件下放置３个月后，固体分散物ⅡＸ－射线衍射图谱出现了尼莫地平结晶峰．     

尼莫地平固体分散体的研究

目的 制备尼莫地平固体分散体,增加其溶出速度.方法 应用聚乙烯吡咯烷酮（PVP）为载体,采用喷雾干燥制备尼莫地平固体分散体,通过差示扫描量热分析（DSC）和X-射线粉末衍射分析鉴别药物在载体中的存在状态,并进行了体外溶出度研究.结果 尼莫地平在载体中以分子状态存在,尼莫地平固体分散体的溶出度与尼莫地平原料药和原料药载体物理混合物相比有显著提高,载体比例越大,药物溶出越快,药物载体比例为1：3时t50仅0.972 6 min,结论聚乙烯吡咯烷酮（PVP）作为尼莫地平固体分散体的载体载药量大;喷雾干燥工艺重现性好,分散体颗粒无需粉碎可满足各类固体制剂的制备要求,是一种较理想的尼莫地平固体分散体的制备方法.     

阿司匹林固体分散物的研究

目的：制备阿司匹林固体分散物;选择了不影响阿司匹林稳定性的ＰＥＧ载体及其合适比例;测定阿司匹林固体分散物的体外溶出速率;分析其结构状态。方法：固体分散物的制备采用熔融法;体外溶出采用浆法;固体分散物的结构分析采用Ｘ－射线衍射法。结果：ＰＥＧ所占比例越大,熔融法制备固体分散物时,阿司匹林的水解程度越低,且ＰＥＧ２０００优于ＰＥＧ６０００;阿司匹林－ＰＥＧ２００００（１：９）固体分散物的标示百分含量为     

西尼地平固体分散物的制备及体外溶出度的测定

目的 通过制备固体分散物提高西尼地平体外溶出速率。方法 以聚乙烯吡咯烷酮（PVP-k30）为载体，采用溶剂—熔融法和物理法制备固体分散物。采用差示扫描量热法（DSC）确定西尼地平以无定型状态分散在载体中，并进行了药物体外溶出度的测定。结果 固体分散物的体外溶出速率明显高于物理混合物的体外溶出速率。DSC图谱检测能充分说明采用溶剂—溶融法能够形成较好的固体分散物，药物与载体的晶体吸收峰已经消失。结论 形成稳定固体分散物后制成制剂，体外溶出度显提高。     

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。     

氯化血红素固体分散物的研制及其分散特征评价

目的:探讨氯化血红素固体分散物的制备及其分散特征的评价.方法:采用溶剂熔融法制备氯化血红素固体分散物,用差示热量扫描(DSC)图谱、红外光谱、X-射线衍射图谱的变化鉴定药物在载体中的分散特征;并对其溶解度和累积溶出速率进行考察.结果:结果显示,以氯化血红素为主药,聚乙二醇6000(PEG6000)为载体制成的固体分散物中,氯化血红素是以分子状态分散在载体中;经溶解度和累积溶出速率的测定,固体分散物溶解度为原药的49倍,固体分散物较原药在30 min时的累积溶出速率提高了22倍.结论:制成固体分散物后,形成填充型固体溶液,氯化血红素的溶解度和溶出速率均得到显著提高,提示本工艺可行,同时也为氯化血红素新制剂的研究提供科学依据.     

阿司匹林固体分散物的研究

目的:制备阿司匹林固体分散物;选择不影响阿司匹林稳定性的PEG 载体及其合适比例;测定阿司匹林固体分散物的体外溶出速率;分析其结构状态。方法:固体分散物的制备采用熔融法;体外溶出采用浆法;固体分散物的结构分析采用X 射线衍射法。结果:PEG 所占比例越大,熔融法制备固体分散物时,阿司匹林的水解程度越低,且PEG20000 优于PEG6000 ;阿司匹林-PEG20000(1∶9) 固体分散物的标示百分含量为104 .68 % ,水杨酸检查合格;与原料药和物理混合物相比,其溶出度显著增加(P< 0 .01) ;该固体分散物中大部分阿司匹林以分子状态分散,只有极少部分以微晶状态分散。结论:以PEG20000 为载体,按阿司匹林 PEG= 1∶9 的比例制备阿司匹林固体分散物是理想的,该分散物体外溶出迅速,可用于制备小规格的片剂,在不影响疗效的前提下,通过减小剂量来降低阿司匹林对胃肠道的刺激性     

尼群地平固体分散体的休外溶出特性

目的：制备尼群地平固体分散体,增加其溶解度和溶出速度。方法：以聚乙二醇6000（PEG6000）、聚乙二醇4000（PEG4000）、聚乙烯吡咯烷酮（PVPk30)为载体,以溶剂－熔融法和共沉淀法制备尼群地平固体分散体。应用差热分析鉴别药物在载体中的存在状态,同时进行溶解测定和溶出度研究。结果：尼群地平与载体形成了共熔物,药物以微细结晶存在于载体中,载体比例越大,药物溶出越快,溶解度越大,结论：尼群地平与3种载体形成的固体散全在水中的溶解度均有显著增加（P＜0．05）。当尼群地平－载体比例达1：4时,尼群地平从固体分散体中的溶出速度明显大于尼群地平纯药和尼发群地平－载体（1：8）物理混合物（P＜0．05）。3种载体中以PVPK30对尼群地平的溶解度及溶出速度增加最为显著。     

卡维地洛固体分散体的制备与溶出度测定

目的：制备卡维地洛固体分散体,增加其溶解度和溶出速度。方法：以聚乙烯吡咯烷酮（PVP）、聚乙二醇－6000（PEG－6000）为载体,溶剂法和溶剂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;且载体比例愈小,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,为难溶于水药物提高生物利用度开辟一条途径。     

Improvement of Oral Absorption of Poorly Water-Soluble Drugs by Solid Dispersions with Amphiphilic Phospholipid Polymer

Solid dispersions are one of methods for solubilizing water-insoluble drugs. To enhance the bioavailability, maintenance of the supersaturated state and absorption of the dissolved drug in the gastrointestinal tract are important. We designed and synthesized amphiphilic 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers as carriers for solid dispersions and evaluated the dissolution behavior in test solutions with different pH and additives. Solid dispersion of troglitazone with amphiphilic MPC copolymers having both aromatic rings and urethane bonds in the side chains showed rapid dissolution and excellent supersaturation maintenance. It was indicated that the balance between the interactions with drug molecules and the water affinity of the polymer should be considered when carriers for solid dispersions are designed. In addition, cell membrane permeability of the solid dispersion with the amphiphilic MPC copolymer was evaluated by the Dissolution / Permeation system, which consists of two liquid chambers and a monolayer of epithelial cells that mimics the intestinal dissolution and permeation process. Further, blood concentration of the drug when solid dispersions were orally administered in mice was also evaluated. The cell membrane permeability and oral absorbability were significantly improved, compared to the solid dispersions with poly(N-vinylpyrrolidone) and suspension or solution of crystalline troglitazone.     

尼莫地平与泊洛沙姆固体分散体的制备及其体外溶出度

采用熔融法制备尼莫地平（１）与泊洛沙姆（２）固体分散体，并测定其体外溶出度，结果均高于１原药。１与２不同比例（１∶１、１∶２、１∶３、１∶５、１∶１０）的固体分散体４５ｍｉｎ时的溶出度分别是原药的６．８、７．３、７．６、８．５、９．８倍。ＤＳＣ测定结果表明，１－２固体分散体的ＤＳＣ曲线中１原药的熔点峰消失。     

Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets

The objective of this study was to compare the dissolution behavior of tablets prepared from solid dispersions with and without drug-carrier interactions. Diazepam and nifedipine were used as model drugs. Two types of carriers were used; polyvinylpyrrolidone (PVP K12, K30 and K60) and saccharides (inulin 1.8?kDa, 4?kDa and 6.5?kDa). Solid dispersions with various drug loads were prepared by lyophilization. It was found that the drug solubility in aqueous PVP solutions was significantly increased indicating the presence of drug-carrier interaction while the drug solubility was not affected by the saccharides indicating absence of drug-carrier interaction. X-ray powder diffraction and modulated differential scanning calorimetry revealed that all solid dispersions were fully amorphous. Dissolution behavior of solid dispersion tablets based on either the PVPs or saccharides was governed by both dissolution of the carrier and drug load. It was shown that a fast drug dissolution of solid dispersions with a high drug load could be obtained with carrier that showed interaction with the drug.     

Silymarin-solid dispersions: characterization and influence of preparation methods on dissolution

The influence of preparation methodology of silymarin solid dispersions using a hydrophilic polymer on the dissolution performance of silymarin was investigated. Silymarin solid dispersions were prepared using HPMC E 15LV by kneading, spray drying and co-precipitation methods and characterized by FTIR, DSC, XRPD and SEM. Dissolution profiles were compared by statistical and model independent methods. The FTIR and DSC studies revealed weak hydrogen bond formation between the drug and polymer, while XRPD and SEM confirmed the amorphous nature of the drug in co-precipitated solid dispersion. Enhanced dissolution compared to pure drug was found in the following order: co-precipitation > spray drying > kneading methodology (p < 0.05). All preparation methods enhanced silymarin dissolution from solid dispersions of different characteristics. The co-precipitation method proved to be best and provided a stable amorphous solid dispersion with 2.5 improved dissolution compared to the pure drug.     

Formulation Development and Dissolution Rate Enhancement of Efavirenz by Solid Dispersion Systems

The aim of this study was to enhance the dissolution rate of efavirenz using solid dispersion systems (binary and ternary). A comparison between solvent and fusion method was also investigated. Solid dispersions of efavirenz were prepared using polyethylene glycol 8000, polyvinylpyrrolidone K30 alone and combination of both. Tween 80 was incorporated to obtain a ternary solid dispersion system. Dissolution tests were conducted and evaluated on the basis of cumulative percentage drug release and dissolution efficiency. Physicochemical characterizations of the solid dispersions were carried out using differential scanning calorimetric, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. Dissolution was remarkably improved in both systems compared to pure efavirenz (P<0.05). An optimum ratio was identified at a drug:polymer of 1:10. Incorporation of Tween 80 to 1:10 formulations formed using solvent method showed further improvement in the dissolution rate. Physicochemical characterization results suggested that efavirenz existed in the amorphous form in all the solid dispersion systems providing evidence of improvement in dissolution. No statistically significant difference (P>0.05) in dissolution was observed between the two methods. Binary and ternary solid dispersion systems both have showed a significant improvement in the dissolution rate of efavirenz. Formulations with only polyvinylpyrrolidone K30 showed best dissolution profile and 1:10 was identified as an optimum drug-polymer weight ratio.     

Properties of solid dispersions of piroxicam in polyvinylpyrrolidone.

Solid dispersions of piroxicam were prepared with polyvinylpyrrolidone (PVP) K-17 PF and PVP K-90 by solvent method. The physical state and drug:PVP interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). FTIR analysis demonstrated the presence of intermolecular hydrogen bonding between piroxicam and PVP in solid dispersions. These interactions reflected the changes in crystalline structures of piroxicam. The amorphousness within the PVP moeity might be predicted in piroxicam dispersions by the disappearance of N-H or O-H peak of piroxicam. Dissolution studies indicated a significant increase in dissolution of piroxicam when dispersed in PVP. The better results were obtained with the lower molecular weight PVP K-17 than with higher molecular weight PVP K-90. The non-amorphous solid dispersions in PVP K-17 showed almost equally fast dissolution rates to amorphous dispersions in PVP K-90. The mechanism of dissolution of solid dispersion in PVP K-90 is predominantly diffusion-controlled due to the very high viscosity of PVP K-90. Dissolution was maximum with the amorphous solid dispersions containing drug:PVP K-17 1:5 and 1:6 which showed a 40-fold increase in dissolution in 5 min as compared with pure drug. Copyright     

In vitro Dissolution Studies on Solid Dispersions of Mefenamic Acid

Solid dispersions of mefanamic acid with a water-soluble polymer polyvinyl pyrrolidine and a super disintegrant, primojel were prepared by common solvent and solvent evaporation methods employing methanol as the solvent. The dissolution rate and dissolution efficiency of the prepared solid dispersions were evaluated in comparison to the corresponding pure drug. Solid dispersions of mefenamic acid showed a marked enhancement in dissolution rate and dissolution efficiency. At 1:4 ratio of mefenamic acid-primojel a 2.61 fold increase in the dissolution rate of mefenamic acid was observed with solid dispersion. The solid dispersions in combined carriers gave much higher rates of dissolution than super disintegrants alone. Mefanamic acid-primojel-polyvinyl pyrrolidine (1:3.2:0.8) solid dispersion gave a 4.11 fold increase in the dissolution rate of mefenamic acid. Super disintegrants alone or in combination with polyvinyl pyrrolidine could be used to enhance the dissolution rate of mefenamic acid.     

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