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。     

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。     

水飞蓟素增溶方法的比较研究

目的：优选增加水飞蓟素溶解度和溶出速度的最佳方法的条件。方法：以聚乙烯吡咯烷酮（PVP）,聚乙二醇6000（PEG-6000）,PEG-6000与Tween-80混合载体。制备固体分散体;以β-CD,HP-β-CD制包合物,测定溶解度及体外溶出速度,结果：水中溶解度PVP固体分散体大于包合物,载体比例越大,药物溶出愈快。比例相同时,PVP固体分散体溶出最快。结论：PVPK30作为水飞蓟素固体分散体的载体。载药量大。增溶效果显著。     

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。     

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。     

米非司酮固体分散体的制备及性质研究

目的:增加米非司酮的溶解度和体外溶出速率,为阴道环的成功制备奠定基础。方法:以PVPK30为载体,采用溶剂法制备米非司酮固体分散体。考察其体外溶出特性,并采用差示扫描量热法、红外光谱法和粉末X-射线衍射法鉴别药物在固体分散体中的存在状态。结果:固体分散体大大提高了米非司酮的溶出速率,最佳比例为1∶3。药物在分散体中以无定型状态存在。结论:溶剂法制备的固体分散体可显著提高药物的溶出速率,从而提高了阴道环中药物的释放量。     

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。     

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。     

伊曲康唑固体分散体制备及体外溶出实验

目的:运用固体分散体技术提高难溶性药物伊曲康唑的溶解度及体外溶出速率.方法:选用聚乙烯吡咯烷酮(PVPK30)为载体,采用喷雾干燥法制备伊曲康唑固体分散体,通过差热分析及X射线衍射对固体分散体进行鉴定,比较考察伊曲康唑及其物理混合物和固体分散体的溶出特性.结果:差热分析、X射线衍射图谱表明药物以无定形状态分散于载体中;体外溶出结果表明固体分散体能显著增加药物在水及人工胃液中的溶出度(45 min时1:4固体分散体体外溶出度为伊曲康唑的11.5倍.1:4固体分散体在0.1 mo1·L-1盐酸中溶解度是伊曲康唑的67倍).结论:伊曲康唑固体分散体能明显提高伊曲康唑的溶解度及体外溶出速率.     

微管蛋白抑制剂SUD-35固体分散体的制备、鉴定及初步体外药效学研究

目的将难溶性微管蛋白抑制剂SUD-35制备成固体分散体,以增加其溶解度及溶出速率。方法以聚乙二醇6000为载体,溶剂-熔融法制备SUD-35固体分散体。采用差示扫描量热分析与X-射线衍射观察药物在载体中的存在状态,并进行溶解度和体外溶出度研究。采用MTT法对SUD-35固体分散体对小鼠白血病L1210细胞药效进行测定。结果 SUD-35固体分散体中SUD-35的溶解度和溶出速率相对原料药和物理混合物均有明显提高,差示扫描量热分析与X-射线衍射结果显示SUD-35以无定型状态存在于固体分散体中,细胞药效结果显示SUD-35固体分散体对小鼠白血病L1210细胞增殖抑制率强于SUD-35纯药。结论聚乙二醇6000为载体制备SUD-35固体分散体,可显著提高SUD-35的溶解度及溶出速率。     

尼美舒利固体分散体的非pH依赖性释放研究

目的以尼美舒利为难溶弱酸性模型药物,研究提高该类药物释放速率的方法。方法以聚乙二醇6000(PEG6000)为载体,采用熔融法制备尼美舒利固体分散体;测定含不同碱化剂(包括NaOH、KOH、Ca(OH)2、Na2CO3、CaCO3)的尼美舒利固体分散体中药物的释放速率。结果加入碱化剂能显著增加尼美舒利在蒸馏水中的释放度,碱化剂不同,药物的释放度不同;碱化剂的碱性越强,分散体的颜色越深,其吸湿性也相对越大。结论在尼美舒利PEG6000固体分散体中加入碱化剂可显著改善该类药物的体外释放特点,并呈现明显的非pH依赖性。     

Unexpected Performance of Physical Mixtures over Solid Dispersions on the Dissolution Behavior of Benznidazole from Tablets

This work investigated the feasibility of developing benznidazole (BZL) tablets, allowing fast, reproducible, and complete drug dissolution, by compressing BZL-Polyethylene Glycol (PEG) 6000 physical mixtures (PMs) and solid dispersions (SDs). SDs were prepared by the solvent evaporation method at different drug:polymer ratios (w/w). BZL-PEG 6000 formulations were characterized by X-ray diffraction (XRD), scanning electron microscopy, and dissolution studies. The preparation of SD-based BZL tablets by the wet granulation method was carried out and the influence of pregelatinized starch (PS) and starch (S) on the disintegration time and drug dissolution rate was analyzed. SDs showed a significant improvement in the release profile of BZL as compared with the pure drug. As demonstrated by XRD, the crystalline character of BZL remained almost unaltered in both PMs and SDs. BZL release from the PEG 6000 tablets increased by the presence of PS instead S. Unexpectedly, the BZL release from tablets containing PMs was almost equal as compared with the BZL release from tablets containing SDs. In conclusion, the results suggest that PEG 6000 and PS are suitable additives for the development of BZL tablets with enhanced dissolution behavior through the preparation of ordinary PMs, instead the laborious SDs. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1016–1023, 2013     

Enhanced dissolution and systemic availability of albendazole formulated as solid dispersions

Solid dispersions (SDs) containing the anthelmintic compound albendazole (ABZ) and either Pluronic 188 (P 188) or polyethylene glycol 6000 (PEG 6000) as hydrophilic carriers were formulated. Drug–polymers interactions in solid state were investigated using different techniques.

Only a 4% of total ABZ was dissolved at 5 min post-incubation, reaching dissolution rates of 32.8% (PEG 6000) and 69.4% (P 188) in SDs. In this way, P 188 was substantially more efficient as ABZ dissolution promoter in comparison to PEG 6000, especially at the initial stages of the dissolution processes (<30 min).

An increased systemic availability (p < 0.001) was obtained when ABZ was administered as ABZ-P 188 SDs, with a 50% enhancement in systemic exposure (AUC values) compared to treatment with an ABZ suspension. Consistently, the Cmax increased 130% (p < 0.001) following treatment with P 188 based SD ABZ formulation. For the ABZ-PEG 6000 SD formulation, the favorable effect on ABZ systemic availability did not reached statistical significance compared to the control group.

The study reported here showed the utility of pharmacokinetic assays performed on mice as a model for preliminary drug formulation screening studies.     

Characterization and Physical Stability of Spray Dried Solid Dispersions of Probucol and PVP-K30

The main purpose of this study was to obtain stable, well-characterized solid dispersions (SDs) of amorphous probucol and polyvinylpyrrolidone K-30 (PVP-K30) with improved dissolution rates. A secondary aim was to investigate the flow-through dissolution method for in-vitro dissolution measurements of small-sized amorphous powders dispersed in a hydrophilic polymer. SDs were prepared by spray drying solutions of probucol and different amounts of PVP-K30. The obtained SDs were characterized by dissolution rate measurements in a flow-through apparatus, X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), particle sizing (laser diffraction) and Brunauer-Emmett-Teller Method (BET) and results were compared with starting material and a physical mixture. The physical stability was monitored after storage at 25°C and 60% RH for up to 12 weeks. The flow-through method was found suitable as dissolution method. All SDs showed improved in-vitro dissolution rates when compared to starting material and physical mixtures. The greatest improvement in the in-vitro dissolution rate was observed for the highest polymer to drug ratio. By means of the results from XRPD and DSC, it was argued that the presence of amorphous probucol improved the dissolution rate, but the amorphous state could not fully account for the difference in dissolution profiles between the SDs. It was suggested that the increase in surface area due to the reduction in particle size contributed to an increased dissolution rate as well as the presence of PVP-K30 by preventing aggregation and drug re-crystallization and by improving wettability during dissolution. The stabilizing effect of the polymer was verified in the solid state, as all the SDs retained probucol in the amorphous state throughout the entire length of the stability study.     

Characterization and physical stability of spray dried solid dispersions of probucol and PVP-K30

The main purpose of this study was to obtain stable, well-characterized solid dispersions (SDs) of amorphous probucol and polyvinylpyrrolidone K-30 (PVP-K30) with improved dissolution rates. A secondary aim was to investigate the flow-through dissolution method for in-vitro dissolution measurements of small-sized amorphous powders dispersed in a hydrophilic polymer. SDs were prepared by spray drying solutions of probucol and different amounts of PVP-K30. The obtained SDs were characterized by dissolution rate measurements in a flow-through apparatus, X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), particle sizing (laser diffraction) and Brunauer-Emmett-Teller Method (BET) and results were compared with starting material and a physical mixture. The physical stability was monitored after storage at 25 degrees C and 60% RH for up to 12 weeks. The flow-through method was found suitable as dissolution method. All SDs showed improved in-vitro dissolution rates when compared to starting material and physical mixtures. The greatest improvement in the in-vitro dissolution rate was observed for the highest polymer to drug ratio. By means of the results from XRPD and DSC, it was argued that the presence of amorphous probucol improved the dissolution rate, but the amorphous state could not fully account for the difference in dissolution profiles between the SDs. It was suggested that the increase in surface area due to the reduction in particle size contributed to an increased dissolution rate as well as the presence of PVP-K30 by preventing aggregation and drug re-crystallization and by improving wettability during dissolution. The stabilizing effect of the polymer was verified in the solid state, as all the SDs retained probucol in the amorphous state throughout the entire length of the stability study.     

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers

This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC_0–24?h and C_max in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL.     

Enhanced solubility and permeability of exemestane solid dispersion powders for improved oral delivery

The aim of the present investigation was to enhance the solubility of exemestane (EXM), by solid dispersion (SD) technique using PEG 6000 as a carrier. Phase solubility studies were conducted with PEG 6000 and PEG 20000 to evaluate the effect of carriers on aqueous solubility of EXM. The aqueous solubility of EXM was favoured with PEG 6000 compared to PEG 20000. SDs of EXM using polyethylene glycol 6000 (PEG 6000) as carrier were prepared in different drug to carrier ratios. Solid-state characterization indicated decrease in crystallinity of the drug. The in vitro dissolution rate of EXM was enhanced from both SDs and tablet formulations prepared using SD compared to pure EXM. The in situ permeability studies investigated using single-pass intestinal perfusion technique in rats revealed increase in effective intestinal permeability (P_eff, cm/s) by 4.45 folds with SDs. Thus, EXM-PEG 6000 SDs showed improved solubility and permeability.     

Roles of MgO release from polyethylene glycol 6000-based solid dispersions on microenvironmental pH,enhanced dissolution and reduced gastrointestinal damage of telmisartan

The roles of magnesium oxide (MgO) release from solid dispersions (SDs) in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and water were investigated to elucidate the enhanced dissolution and reduced intestinal damages of telmisartan as a model drug. The polyethylene glycol 6000 (PEG 6000) was used to prepare the SDs. Three SDs were prepared: SD1 (PEG, MgO, TEL), SD2 (PEG 6000, TEL), SD3 (MgO, TEL). The physical mixture (PM) consisting of SD2 and MgO was also prepared. A binary SD without MgO (SD2) was also prepared for comparison in microenvironmental pH (pH_M) modulation. The faster MgO released, the less control of pH_M and the less enhanced dissolution of TEL were in consequences. SD3 increased dissolution in SIF and water (about 67%). Interestingly, ternary SD1 showed almost complete dissolution in all three media but dissolution of PM was the lowest due to the fast release of MgO and poor modulation of pH_M. MgO did not change the drug crystallinity but did have a strong molecular interaction with the drug. Additionally, the SD3-bearing tablet quickly increased pH_M but then gradually decreased due to faster release of MgO while the SD1-bearing tablet gradually increased pH_M at all fractional dimensions of the tablet by the MgO slowly released. The pH_M of PM-bearing tablets was not varied as a function of time. Thus, the MgO-bearing SD1 also minimized gastrointestinal tissue damage caused by the model drug.     

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。