依折麦布混悬剂的制备及药物动力学研究

目的制备依折麦布/介孔硅固体分散体,以该固体分散体制备混悬剂,研究固体分散体和三甲基壳聚糖(TMC)对依折麦布药物动力学的影响。方法采用溶剂挥发法制备依折麦布/介孔硅固体分散体,以溶出度为指标筛选制备方法,采用差示扫描量热(DSC)、扫描电镜(SEM)等技术考察药物存在状态及物理稳定性。以甲基纤维素和TMC分别为助悬剂,将依折麦布/介孔硅固体分散体制成混悬液,研究大鼠口服各混悬液的药物动力学。结果依折麦布与介孔硅质量比为1∶5,搅拌时间为6h,制得固体分散体的载药量为16.5%,药物以非晶状态存在,溶出度可达92.2%,AUC和Cmax提高显著,tmax无明显变化。结论应用该固体分散技术和三甲基壳聚糖能改善依折麦布的口服吸收,提高生物利用度。     

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。     

瑞戈非尼固体分散体的制备及体外溶出度考察

目的采用固体分散技术提高难溶性药物瑞戈非尼的体外溶出度。方法选用聚维酮K30为载体,以溶剂法制备不同比例的瑞戈非尼固体分散体;采用紫外分光光度法测定其溶出度;采用X-射线粉末衍射法分析药物在固体分散体中的存在状态。结果瑞戈非尼固体分散体的溶出度较原料药、物理混合物均有显著提高,且载体比例越大,固体分散体溶出度越大;瑞戈非尼以无定形态分散在载体中。结论采用固体分散技术可有效提高瑞戈非尼的体外溶出度。     

塞来昔布/介孔硅SBA-15固体分散体的制备和性质研究

目的制备塞来昔布(CEL)/介孔硅SBA-15的固体分散体并进行性质研究。方法利用溶剂吸附平衡法制备CEL/SBA-15固体分散体,通过测定表观溶解度考察水溶性,通过热分析(DSC)和溶出试验考察药物溶出行为、药物存在状态及物理稳定性。结果确定了CEL/SBA-15固体分散体的制备方法。固体分散体载药量约37%,溶解度约为原料药的2倍以上,30 min内药物的累计溶出就超过90%,药物以非晶状态存在,加速试验6个月溶出和存在状态稳定。结论 CEL/SBA-15固体分散体物理稳定性良好,明显提高难溶药物的水溶性和溶出速率,改善药物的口服吸收。     

以介孔硅为基质的固体分散体片剂的制备与性质考察

目的将替米沙坦与介孔硅制备成片剂,并考察片剂的稳定性。方法在处方筛选的基础上,采用粉末直接压片法压制替米沙坦-介孔硅片剂;采用高效液相色谱法测定药物含量;采用示差扫描量热、X-射线衍射和溶出法考察制剂的晶型稳定性。结果替米沙坦-介孔硅分散体66 g、交联聚乙烯吡咯烷酮30 g、微晶纤维素50 g、甘露醇50 g、硬脂酸镁4 g,混合均匀,压制成1 000片,含量均匀度和溶出度符合要求,在12个月内替米沙坦稳定性良好,且一直以无定型状态存在。结论利用自制介孔硅制备固体分散体,介孔硅的孔道使难溶性药物长期以无定型状态存在,故制剂稳定性良好。     

阿司匹林固体分散体及其胶囊的制备与体外溶出度研究

目的:制备阿司匹林固体分散体及其胶囊,并研究其体外溶出度。方法:以聚乙烯吡咯烷酮为载体,采用喷雾干燥法制备阿司匹林固体分散体,比较阿司匹林原料药、阿司匹林与载体不同比例的物理混合物和固体分散体的溶出度;采用X-射线衍射和扫描电镜考察药物在载体中的分散状态,测定比表面积;考察阿司匹林固体分散体胶囊的体外溶出度。结果:与阿司匹林原料药、阿司匹林物理混合物比较,阿司匹林固体分散体中药物的溶出度均有提高,且载体比例越大,药物溶出越快,但药物-载体比例达1∶6以上时,溶出度增加不再明显;阿司匹林以无定型或分子形式高度分散在载体中;药物-载体在l∶6时,阿司匹林固体分散体比阿司匹林原料药的比表面积增大3.2倍;制成固体分散体胶囊后,30 min时药物累积溶出度达99.8%。结论:该固体分散体制备工艺可行,制备的胶囊质量可控。     

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.     

喷雾干燥法制备阿司匹林固体分散体及其胶囊制备与体外特性研究

目的 制备阿司匹林固体分散体及其胶囊,提高其溶出度。方法 以聚乙烯吡咯烷酮(PVP K 30)为载体,采用喷雾干燥法制备阿司匹林固体分散体,测定溶出度,采用X-射线衍射和扫描电镜(SEM)考察药物在载体中的分散状态,测定比表面积;制备阿司匹林固体分散体胶囊,考察胶囊的体外溶出度。结果 与阿司匹林原料药、阿司匹林物理混合物相比,阿司匹林固体分散体中药物的溶出度均有显著提高,且载体比例越大,药物溶出越快,但药物和载体比例达1∶6以上时,溶出度增加不再明显。阿司匹林以无定型或分子形式高度分散在载体中,药辅比在l∶6时,阿司匹林固体分散体比阿司匹林原料药的比表面积增大3.2倍;制成固体分散体胶囊后,30 min时药物累积溶出度达99.8%。结论 该固体分散体制备工艺可行,制备的胶囊质量可控。     

壬二酸固体分散体的制备及其表征

目的:制备壬二酸固体分散体,改善壬二酸的溶出度,从而提高其生物利用度。方法:分别以聚乙二醇6000(PEG)、泊洛沙姆188为载体并选取药物与其不同比例(1:3、1:6、1:9),采用熔融法、溶剂-熔融法制备壬二酸固体分散体,并对其进行体外溶出度的考察及比较;采用差示扫描量热法、X射线粉末衍射法鉴别壬二酸在固体分散体中的存在状态。结果:以PEG为载体的固体分散体的药物溶出优于以泊洛沙姆188为载体的固体分散体(90min内溶出分别为100%和80%);且当药物与PEG的比例为1:9时,药物的溶出效果最好,与原料药比较药物溶出50%所需的时间大大缩短(12.65、45.65min)。壬二酸-PEG固体分散体中药物部分呈分子状态分散,部分呈微晶状态分散。结论:壬二酸与PEG(1:9)的固体分散体能显著提高药物的溶出度。     

姜黄素-聚维酮固体分散体的制备及溶出度的测定

目的:制备姜黄素－聚维酮固体分散体,改善姜黄素的溶出度.方法:应用聚乙烯吡咯烷酮(PvPk30)为载体,以溶剂法制备固体分散体,差示扫描量热法、X-射线粉末衍射进行物相鉴定,并测定溶出度.结果:姜黄素在固体分散体中可能以无定型态或分子状态存在,药物的累积溶出百分率随栽体比例增加而增加,以1:6的比例效果最好.制成固体分散体后,药物在水中的溶解度达66.28 g·L-1.结论:采用PVPk30制备的固体分散体能显著提高姜黄素的溶出度.     

扎鲁司特介孔二氧化硅固体分散体的制备及其体外释放考察

目的 制备扎鲁司特（zafirlukast,ZLST）介孔二氧化硅固体分散体,提高体外溶出速度。方法 通过溶胶凝胶法制得介孔二氧化硅（MCM-41）,将其甲基化改性（MCM-41CH₃）;采用浸渍挥干法将ZLST载入,测定体外溶解速度;并采用X射线衍射、差示扫描量热、傅立叶变换红外光谱、扫描电镜、透射电镜等手段对固体分散体进行表征。结果 药物介孔二氧化硅固体分散体可以显著地加快药物的溶出速度,ZLST-MCM-41的释放率略高于ZLST-MCM-41CH₃;物相鉴定表明,ZLST以无定型或微晶形式分散于介孔载体中。结论 介孔二氧化硅可以作为ZLST优良的载体材料。     

Formulation and evaluation of fast dissolving tablets of haloperidol solid dispersion

PurposeThe aim of this study was to design fast dissolving tablets (FDT) of the anti –psychiatric drug haloperidol in solid dispersion forms as a way to enhance its dissolution profile and anti-psychiatric effect.MethodsSolubility studies of haloperidol in various polymers solutions were investigated. The selected polymer with high drug solubility (Poly ethylene glycol 4000) was used for preparation of solid dispersion through two methods solvent evaporation method and melting method. Haloperidol solid dispersion mixed with other solid powder excipients and compressed into tablets. The resulted tablets were evaluated according to British Pharmacopoeia (B.P.) specifications. Pre- and post -compression studies were performed to determine the flow properties and evaluate the solid dispersion systems, followed by in vivo studies through forced swimming test (FST)ResultsPre-compression studies showed adequate flowability and compatibility of polymer and solid excipients with haloperidol. The selected solid dispersion tablet (SD2) demonstrated the best disintegration and water absorption ratio in addition to satisfactory friability and hardness. Attempts of in vitro dissolution results and thermodynamic stability studies showed acceptable results for (SD2) formulation containing PEG 4000 polymer prepared by melting method.The in vivo study of (SD2) formulation revealed the highest immobility time to rats compared to control rats and others treated with commercial haloperidol product.ConclusionFast dissolving tablets prepared from solid dispersion of haloperidol with PEG4000 expressed rapid onset of action with enhanced anti-psychiatric effect of haloperidol.     

Adsorption and Entrapment of Salicylamide Molecules into the Mesoporous Structure of Folded Sheets Mesoporous Material (FSM-16)

Purpose. The aim of this study was to estimate the molecular state of salicylamide on the surface of mesoporous silicas and to investigate the dissolution behavior of salicylamide from the solid dispersion. Methods. Folded sheets mesoporous material (FSM-16) were used as a porous material. The molecular state of salicylamide was estimated by powder X-ray diffractometry, infrared spectroscopy, and fluorescence spectroscopy. Results. The molecular state of salicylamide can be changed by simple blending with FSM-16. When a physical mixture of 25% salicylamide and 75% FSM-16 was heated at 120°C for 3 h, amorphization of salicylamide was observed from the powder X-ray diffraction pattern. The fluorescence emission peak of salicylamide at 433.5 nm shifted to a longer wavelength of 447.5 nm after heating. Changes in fluorescence decay curve suggested that salicylamide molecules were dispersed into the hexagonal FSM-16 channels during the heating process. Enhanced dissolution in the initial stage of salicylamide from the sealed heated sample was observed in comparison with salicylamide crystals. Conclusions. Heat treatment of a physical mixture of salicylamide with FSM-16 gave a solid dispersion in which the salicylamide molecules changed to an amorphous state by adsorption onto the FSM-16 channels. Amorphization of salicylamide contributed to the improvement of dissolution.     

Extruded Soluplus/SIM as an oral delivery system: characterization,interactions, in vitro and in vivo evaluations

Abstract

The aim of this study was to obtain a stable, amorphous solid dispersion (SD) with Soluplus, prepared by hot-melt extrusion (HME) as an effective and stable oral delivery system to improve the physical stability and bioavailability of the poorly water-soluble simvastatin (SIM), a drug with relatively low Tg. The drug was proved to be miscible with Soluplus by calculation and measurements. The solubility, dissolution, thermal characteristics, interactions and physical stability of the SIM/Soluplus SDs were investigated. The crystal state of simvastatin in the SD was found to change from crystalline to amorphous form during the HME process and also hydrogen bonds were observed between SIM and the extruded Soluplus. The phase solubility showed the solubilization effect of Soluplus was strong and spontaneous. The equilibrium solubility illustrated that Soluplus/SIM SDs gained much higher solubility than its corresponding physical mixtures (PMs). Both of the dissolution profiles and in-vivo performance showed that the SIM/Soluplus SD obtained a marked enhancement, compared with the PM. There was a little change in the SIM/Soluplus SD during a 3-month storage period (40?°C, 75%), indicating the good physicochemical stability. The extruded Soluplus system prepared by HME is a good alternative for the water-insoluble SIM to improve the stability and bioavailability.     

介孔二氧化硅微球的制备及用于吲哚美辛载药与溶出性质

目的制备介孔二氧化硅微球,以期提高吲哚美辛的溶出速率。方法以表面活性剂十六烷基三甲基溴化铵和普兰尼克三嵌段共聚物P123作为双模板,用软膜板法制备具有介孔孔道的介孔二氧化硅微球药物载体,采用扫描电镜及氮气吸附-脱附手段表征载体形貌、比表面积及孔径分布。用吸附平衡挥干法载药制得吲哚美辛固体分散体,并对该固体分散体的溶出性质进行研究。结果制得的介孔二氧化硅载体由粒径相对均一的球形粒子组成。其粒径主要集中在2～5μm,载体的比表面积为502.87 m²·g2·g^(-1),孔容为2.23 cm(-1),孔容为2.23 cm³·g3·g^(-1),孔径为23.75 nm。吲哚美辛/介孔二氧化硅固体分散体的药物溶出速率与累积溶出度与吲哚美辛原料药相比均有了显著提高。结论吲哚美辛已高度分散于微球载体中,药物的溶出速率明显加快,为提高吲哚美辛生物利用度的研究打下了基础。     

介孔二氧化硅纳米粒的制备及对载药与药物溶出度的影响

目的为提高水难溶性药物的分散性及溶出度,制备介孔二氧化硅纳米粒作为水难溶性药物的载体。方法探索得到简单有效地制备球状介孔二氧化硅纳米粒的工艺条件,采用扫描电镜及氮气吸附-脱附等手段分析表征载体的外观形貌,比表面积及孔径分布,并选取水难溶性药物西洛他唑作为模型药物,以溶剂浸渍挥干法载药制得药物固体分散体,采用热分析、氮气吸附-脱附曲线以及溶出度实验研究药物固体分散体的基本性质。结果制得的二氧化硅载体的形貌近球状,粒径大小分布在200～250 nm,载体的比表面积最高可达1 101.54 m2.g-1,孔径分布主要集中在3.0～4.0 nm。载药过程对西洛他唑在载体中的存在形式没有影响,固体分散体中西洛他唑的溶出度得到显著提高,当药物与载体的质量比为1∶3时,药物60 min累计溶出达85%。结论介孔二氧化硅纳米粒有望成为水难溶性药物的优良载体。     

Improving anti-tumor activity of sorafenib tosylate by lipid- and polymer-coated nanomatrix

In the present study, we select the Sylysia 350 (Sylysia) as mesoporous material, distearoylphosphatidylethanolamine-poly(ethylene glycol)₂₀₀₀ (DSPE-PEG) as absorption enhancer and hydroxy propyl methyl cellulose (HPMC) as crystallization inhibitor to prepare sorafenib tosylate (SFN) nanomitrix (MSNM@SFN) for improving the anti-tumor activity of SFN. The MSNM@SFN was prepared by solvent evaporation method. The solubility, dissolution, and bioavailability of SFN in MSNM@SFN were also investigated. The anti-tumor activity of MSNM@SFN was evaluated in vitro and in vivo. Our results indicated that the solubility and dissolution of SFN in MSNM@SFN were significantly increased. The oral bioavailability of SFN in MSNM@SFN was greatly improved 7.7-fold compared with that in SFN suspension. The enhanced anti-tumor activity of MSNM@SFN was confirmed in vitro and in vivo experiments. This nanomatrix developed in this study could be a promising drug delivery platform for improving the therapeutic efficacy of poorly water-soluble drugs.     

Mesoporous silica formulation strategies for drug dissolution enhancement: a review

Introduction: Silica materials, in particular mesoporous silicas, have demonstrated excellent properties to enhance the oral bioavailability of poorly water-soluble drugs. Current research in this area is focused on investigating the kinetic profile of drug release from these carriers and manufacturing approaches to scale-up production for commercial manufacture.

Areas covered: This review provides an overview of different methods utilized to load drugs onto mesoporous silica carriers. The influence of silica properties and silica pore architecture on drug loading and release are discussed. The kinetics of drug release from mesoporous silica systems is examined and the manufacturability and stability of these formulations are reviewed. Finally, the future prospects of mesoporous silica drug delivery systems are considered.

Expert opinion: Substantial progress has been made in the characterization and development of mesoporous drug delivery systems for drug dissolution enhancement. However, more research is required to fully understand the drug release kinetic profile from mesoporous silica materials. Incomplete drug release from the carrier and the possibility of drug re-adsorption onto the silica surface need to be investigated. Issues to be addressed include the manufacturability and regulation status of formulation approaches employing mesoporous silica to enhance drug dissolution. While more research is needed to support the move of this technology from the bench to a commercial medicinal product, it is a realistic prospect for the near future.