不同载体他克莫司固体分散体的制备及溶出特性

分别将5种不同的载体[聚乙二醇(PEG)4000、聚维酮(PVP)K30、泊洛沙姆188、聚氧乙烯月桂醚(Brij35)和羟丙甲纤维素(HPMC)]和他克莫司溶于有机溶剂中,采用湿法制粒技术制备固体分散体.用体外溶出度、差示扫描量热(DSC)和X射线衍射(XRD)法比较了各种固体分散体的特性.与相应的物理混合物相比,各固体分散体的溶出度均显著增加.不同载体制得的固体分散体对他克莫司溶出度的增加程度不同.在这5种载体中,以PVP K30和HPMC为载体的固体分散体的溶出情况较接近参比制剂(Prograf).DSC和XRD分析结果显示,以PVP K30和HPMC为载体的他克莫司固体分散体中以晶体状态存在的药物量较少.     

甘草黄酮固体分散体的制备及体外溶出性能考察

目的:制备甘草黄酮(LF)-聚乙烯吡咯烷酮K30(PVP K30)固体分散体,并对其进行表征及体外释药性能考察。方法:分别以聚乙烯吡咯烷酮K30(PVP K30)、聚乙二醇(PEG 4000、 PEG 6000)、泊洛沙姆188(F68)以及胶态二氧化硅(SiO2)为载体,采用溶剂法或溶剂熔融法制备固体分散体,考察其体外释药性能,并利用差式扫描量热仪(DSC)、傅里叶变换红外光谱(FT-IR)对固体分散体的结构特征进行表征。结果:以PVP K30为载体制备的固体分散体的体外溶出率优于其他载体制备的固体分散体,且以药物-载体比例1∶5时溶出度最佳。经DSC和FT-IR结果表明,固体分散体中的药物以无定形状态存在。结论:固体分散体技术能显著提高甘草黄酮的体外溶出度。     

瑞格列奈固体分散体的制备及体外溶出

目的制备瑞格列奈的固体分散体,提高瑞格列奈的体外溶出度。方法以聚乙二醇6000(polyethylene glycol 6000,PEG6000)作为载体,采用溶剂-熔融法制备不同处方的瑞格列奈固体分散体,进行溶出度考查。采用红外光谱、差示扫描量热(differential scanning calorimetry,DSC)与X-射线衍射(X-ray diffraction,XRD)对瑞格列奈固体分散体进行物相分析。结果与瑞格列奈原料和物理混合物相比,固体分散体可显著提高瑞格列奈的体外溶出度,物相鉴定表明,瑞格列奈大部分以无定形状态分散于PEG6000中,提高了药物的体外溶出度。结论制备瑞格列奈的PEG6000固体分散体能显著提高药物的体外溶出度,可满足速释制剂的要求。     

总藤黄酸固体分散体的制备及体外溶出度试验

目的 制备总藤黄酸固体分散体并对其溶出度进行测定.方法 以聚乙二醇4000、聚乙二醇6000、聚乙烯吡咯烷酮K15、聚乙烯吡咯烷酮K30为载体,分别采用溶剂法、溶剂-熔融法制备总藤黄酸固体分散体,同时对其体外溶出度进行测定.结果 以PVP-K30为载体,配比为1：3的固体分散体溶出度显著提高.     

格列喹酮固体分散体的制备及溶出度测定

目的:制备格列喹酮固体分散体并考察其体外溶出性。方法:以聚乙烯吡咯烷酮K30(PVP)、聚乙二醇6000(PEG)为载体,溶剂熔融法和溶剂法制备格列喹酮固体分散体,并与原料药比较体外溶出度。结果:载体比例越大,药物溶出愈快。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者。格列喹酮-PVP固体分散体(1∶7)10min内体外溶出度达到70%以上,优于格列喹酮原料药。结论:成功制备了格列喹酮固体分散体。     

盐酸胺碘酮固体分散体的制备及溶出度测定

目的制备盐酸胺碘酮固体分散体,测定其体外溶出度,同时与普通胶囊剂的体外溶出度比较。方法以聚乙二醇6000(PEG6000)为载体,溶剂熔融法制备盐酸胺碘酮固体分散体,用紫外分光光度法测定体外溶出度。结果盐酸胺碘酮固体分散体的体外溶出度比普通胶囊剂显著提高。结论成功制备了盐酸胺碘酮固体分散体。     

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。     

阿德福韦酯-PEG6000固体分散体的制备

目的将难溶性药物阿德福韦酯制备成固体分散体,以增加体外溶出度。方法以聚乙二醇6000(polyethylene glycol 6000,PEG6000)为载体,采用熔融法制备阿德福韦酯固体分散体;配合差示扫描量热(differential scanning calorimetry,DSC)与X-射线衍射(X-ray diffraction,XRD)观察药物在载体中的存在状态;考察相对湿度(relative humidity,RH)75%40℃放置3个月固体分散体对溶出度的变化及载体-药物质量比对溶出的影响。结果阿德福韦酯以无定型状态存在于固体分散体中,相对湿度RH75%40℃放置3个月固体分散体对溶出度改善明显,载体-药物质量比不同,药物的溶出度不同。结论将阿德福韦酯制成固体分散体能显著增加阿德福韦酯的体外溶出度。     

索法酮固体分散体的制备及体外溶出度的研究

目的:提高制剂中索法酮体外溶出度.方法:选择水溶性载体聚乙二醇4000(PEG4000)和聚乙烯吡咯烷酮K30(PVPk30)用熔融法制备索法酮固体分散体,建立紫外-可见分光光度法测定固体分散体的溶出度的方法.结果:紫外-可见分光光度法测定索法酮的溶出度,方法准确可靠、稳定且无载体的干扰.制备的固体分散体能显著地提高索法酮的体外溶出度;以聚乙二醇(PEG4000)为载体制备的固体分散体溶出度高于聚乙烯吡咯烷酮K30(PVPk30).差示扫描热量法(DSC)研究表明,在质量比为1:8索法酮一聚乙二醇4000(PEC4000)固体分散体中,索法酮以无定形的状态分散在固体分散体中,其熔点吸热峰消失.结论:索法酮固体分散体的体外溶出度增大,与载体的结构及其在良好载体固体分散体中的无定形状态有关.     

穿心莲内酯聚丙烯酸树脂Ⅱ固体分散体的制备及表征

目的：研究无定形聚合物聚丙烯酸树脂Ⅱ（Eudragit Ⅱ）制备的穿心莲内酯固体分散体的优良性质,为固体分散体的载体选择提供参考依据。方法：以无定形聚合物Eudragit Ⅱ为载体材料,按穿心莲内酯-载体质量比为1：3,采用喷雾干燥法制备穿心莲内酯固体分散体,并用傅里叶变换红外光谱（FTIR）、热重分析（TG）、X-射线衍射（XRD）、差示扫描量热（DSC）、扫描电镜（SEM）、比表面积、粒径和溶出度测定穿心莲内酯固体分散体的理化性质及溶出行为。结果：FTIR光谱和TG分析说明在穿心莲内酯固体分散体和物理混合物中穿心莲内酯与Eudragit Ⅱ之间都存在分子间相互作用,其中穿心莲固体分散体具有更好的热稳定性;DSC和XRD分析说明无定形载体Eudragit Ⅱ制备的固体分散体中穿心莲内酯主要以无定形形式存在;SEM显示,固体分散体中穿心莲内酯由块状晶体形态变为了不规则的圆形形态;同时与物理混合物相比,穿心莲内酯固体分散体具有更大的比表面积、更大的孔体积和更小的粒径等粉体学性质;溶出实验表明穿心莲内酯固体分散体具有增大溶出的优势,效果明显。结论：以无定形载体Eudragit Ⅱ制备的穿心莲内酯固体分散体具有优良的理化性质,同时比表面积大,孔体积大的特征更有利于水分子的进入,从而有效地增大穿心莲内酯的溶出速率。     

复合载体齐墩果酸固体分散体的制备及评价

目的：制备复合载体齐墩果酸固体分散体,提高齐墩果酸的溶出度。方法：采用溶剂法,以聚乙烯吡咯烷酮（PVP VA64）和聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物（Soluplus）为复合载体,制备齐墩果酸固体分散体,以累积溶出度为评价指标,考察不同载体比例,药物与载体比例,筛选最佳工艺。通过差式扫描量热法（DSC）、扫描电镜（SEM）、傅里叶红外光谱（FTIR）、粉末X 射线衍射（XRPD）等技术手段对其表征,并考察其溶出度。结果：Soluplus和PVP VA64复合载体比例为3∶2,药物与载体比例为1∶7,制备固体分散体,在45 min时累积溶出度为92.43%,DSC、SEM、XRPD、FTIR等表征结果显示药物以无定形状态存在于固体分散体中,且药物与载体之间存在氢键相互作用。结论：Soluplus和PVP VA64作为复合载体材料,联合应用可显著提高齐墩果酸的体外溶出度。     

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.     

芒果苷PVP固体分散体的制备和表征及在体外肠道菌群模型中的代谢

目的：制备芒果苷（MGF）聚乙烯吡咯烷酮（PVP）固体分散体（MGF-SD）,提高MGF的溶解度和溶出速度,并对比考察MGF、MGF-SD在体外肠道菌群模型中的代谢差异。方法：以PVP为载体材料,采用共沉淀法制备MGF固体分散体,通过差示扫描量热法（DSC）、X射线粉末衍射法（XRD）和红外光谱（IR）表征其物相特征。采用摇瓶法测定MGF、MGF-SD溶解度。采集健康志愿者新鲜粪便,制备肠道菌群混悬液,分别与MGF、MGF-SD在厌氧环境下孵育,HPLC法监测MGF含量变化。结果：当MGF与PVP的质量比分别为1∶2,1∶4,1∶9时,MGF溶解度分别提高了432,513,633倍。DSC、XRD和IR均显示,MGF-SD中MGF晶体结构发生破坏,以非晶状态存在。体外释放度测定结果表明,MGF-SD中MGF释放速度快于MGF原料。与MGF原料相比,MGF制备成固体分散体后,离体人肠道菌群对MGF的代谢速度降低。结论：MGF制备成PVP固体分散体后,MGF以非晶型分子状态高度分散在载体材料中,MGF溶出度与溶解度显著提高,同时可减慢肠道菌群对MGF的代谢,有利于提高MGF口服生物利用度。     

托伐普坦固体分散体的制备及体外溶出特性考察

目的 采用固体分散技术提高难溶性药物托伐普坦的体外溶出度。方法 选用聚维酮K_29/32为载体材料,以溶剂蒸发法制备托伐普坦固体分散体。采用差示扫描量热法(DSC)、X-射线粉末衍射法(XRPD)对所得固体分散体进行鉴定, 并进行溶解度、体外溶出实验。结果 固体分散体的DSC 图谱及X-射线粉末衍射确定了托伐普坦以无定形态分散在载体中, 体外溶解实验表明其溶出较原料药、物理混合物均有明显提高。结论 将托伐普坦与PVP K_29/32制成固体分散体,其分散状态发生了改变,溶出性能明显提高。     

Physicochemical characterisation,drug polymer dissolution and in vitro evaluation of phenacetin and phenylbutazone solid dispersions with polyethylene glycol 8000

Poor water solubility leads to low dissolution rate and consequently, it can limit bioavailability. Solid dispersions, where the drug is dispersed into an inert, hydrophilic polymer matrix can enhance drug dissolution. Solid dispersions were prepared using phenacetin and phenylbutazone as model drugs with polyethylene glycol (PEG) 8000 (carrier), by melt fusion method. Phenacetin and phenylbutazone displayed an increase in the dissolution rate when formulated as solid dispersions as compared with their physical mixture and drug alone counterparts. Characterisation of the solid dispersions was performed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). DSC studies revealed that drugs were present in the amorphous form within the solid dispersions. FTIR spectra for the solid dispersions of drugs suggested that there was a lack of interaction between PEG 8000 and the drug. However, the physical mixture of phenacetin with PEG 8000 indicated the formation of hydrogen bond between phenacetin and the carrier. Permeability of phenacetin and phenylbutazone was higher for solid dispersions as compared with that of drug alone across Caco‐2 cell monolayers. Permeability studies have shown that both phenacetin and phenylbutazone, and their solid dispersions can be categorised as well‐absorbed compounds. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4281–4294, 2011     

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.     

Dissolution Improvement of Atorvastatin Calcium using Modified Locust Bean Gum by the Solid Dispersion Technique

The present research was aimed at the enhancement of the dissolution rate of atorvastatin calcium by the solid dispersion technique using modified locust bean gum. Solid dispersions (SD) using modified locust bean gum were prepared by the modified solvent evaporation method. Other mixtures were also prepared by physical mixing, co-grinding, and the kneading method. The locust bean gum was subjected to heat for modification. The prepared solid dispersions and other mixtures were evaluated for equilibrium solubility studies, content uniformity, FTIR, DSC, XRD, in vitro drug release, and in vivo pharmacodynamic studies. The equilibrium solubility was enhanced in the solid dispersions (in a drug:polymer ratio of 1:6) and other mixtures such as the co-grinding mixture (CGM) and kneading mixture (KM). Maximum dissolution rate was observed in the solid dispersion batch SD3 (i.e. 50% within 15 min) with maximum drug release after 2 h (80%) out of all solid dispersions. The co-grinding mixture also exhibited a significant enhancement in the dissolution rate among the other mixtures. FTIR studies revealed the absence of drug-polymer interaction in the solid dispersions. Minor shifts in the endothermic peaks of the DSC thermograms of SD3 and CGM indicated slight changes in drug crystallinity. XRD studies further confirmed the results of DSC and FTIR. Topological changes were observed in SEM images of SD3 and CGM. In vivo pharmacodynamic studies indicated an improved efficacy of the optimized batch SD3 as compared to the pure drug at a dose of 3 mg/kg/day. Modified locust bean gum can be a promising carrier for solubility enhancement of poorly water-soluble drugs. The lower viscosity and wetting ability of MLBG, reduction in particle size, and decreased crystallinity of the drug are responsible for the dissolution enhancement of atorvastatin. The co-grinding mixture can be a good alternative to solid dispersions prepared by modified solvent evaporation due to its ease of preparation and significant improvement in dissolution characteristics.     

Physical properties and dissolution behaviour of nifedipine/mannitol solid dispersions prepared by hot melt method

Solid dispersions of nifedipine (NIF) with mannitol in preparations containing 10 and 50% (w/w) of drug were manufactured by the hot melt method. Physical properties and the dissolution behaviour of binary systems as physical mixtures and solid dispersions were investigated. In all samples, the crystal structure of NIF was confirmed using differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) revealed, there was no interaction between drug and carrier, however, FTIR spectra indicated formation of thermodynamically less stable polymorph of mannitol. The dissolution rate of NIF from solid dispersions was markedly enhanced, the effect being stronger at higher drug loading (50%, w/w, NIF). The dissolution rate enhancement was attributed to improved wetting of NIF crystals due to mannitol particles, attached on the surface, as inspected by means of SEM. Thermal stability of NIF, mannitol and two other potential carbohydrate carriers (lactose and saccharose) during the hot melt procedure was investigated using 1H NMR. NIF was found to be thermically stable under conditions applied. As expected, among carriers only mannitol demonstrated suitable resistance to high temperature used in experiments.     

间尼索地平固体分散体的研制

目的:将难溶性药物间尼索地平制备成固体分散体,以增加其溶解度及体外溶出度。方法:以泊洛沙姆为载体,共沉淀法制备间尼索地平固体分散体。采用差示扫描量热分析(DSC)方法鉴别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。结果:DSC显示间尼索地平与泊洛沙姆形成了低共熔物,间尼索地平原料药及其与泊洛沙姆不同比例的固体分散体(1∶3、1∶5、1∶7)的溶解度分别为0.89、4.50、15.35、23.03mg·L-1,120min时的累积溶出百分率分别为26.80%、38.57%、41.38%、45.92%,固体分散体的溶出度高于同比例的物理混合物。结论:以泊洛沙姆为载体制备间尼索地平固体分散体,可增加药物的体外溶出度和溶解度。