复方珍珠粉泡腾颗粒处方筛选及溶出度考察

目的:筛选复方珍珠粉泡腾颗粒处方并考察其在不同介质中的体外溶出度。方法:以乙二胺四乙酸消耗量为指标,兼顾发泡高度和pH值,用均匀设计法筛选处方中无水柠檬酸、碳酸氢钠、乳糖的量;考察并比较复方珍珠粉泡腾颗粒、自制碳酸钙片、自制珍珠粉片中碳酸钙在蒸馏水和盐酸中的溶出度。结果:处方中无水柠檬酸、碳酸氢钠、乳糖的量分别为10.0、2.5、5.0g;3种制剂间的溶出度有明显差异。结论:制备的复方珍珠粉泡腾颗粒释药速度快、药物溶出完全,溶液呈酸性,适合特定人群使用。     

复方碳酸钙泡腾颗粒剂处方筛选及吸湿性考察

目的 优化复方碳酸钙泡腾颗粒剂处方组成,并对优化处方制备的泡腾颗粒剂进行吸湿性考察。方法 以干燥失重％为指标,均匀试验设计筛选复方碳酸钙泡腾颗粒剂处方中乳糖、山峰果醇、PVP等辅料的用量,建立吸湿性曲线方程,考察泡腾颗粒剂不同湿度下放置的吸湿性。结果 本品在相对湿度75％以下放置吸湿性小于5％。结论 优化处方后制成的炮腾颗剂具有很好的稳定性。     

复方碳酸钙泡腾颗粒剂人体相对生物利用度研究

目的考察复方碳酸钙颗粒剂的人体相对生物利用度。方法以钙尔奇D600为对照品,原子吸收分光光度法测定12名自愿受试者口服复方碳酸钙颗粒剂后的尿钙排泄量。结果在12h内,复方碳酸钙颗粒剂组,钙尔奇D组和空白对照组的平均尿钙排泄总量分别为125.21±26.60,124.49±36.60和67.24±19.39mg。集尿期内复方碳酸钙颗粒剂和钙尔奇D尿钙排泄总量的净增值分别为57.97±24.24和57.31±32.68mg。复方碳酸钙颗粒剂的相对生物利用度101.50%。结论两种药物的吸收程度相当,无统计学差异(P＞0.05),由尿钙排泄速率推测,复方碳酸颗粒剂的吸收速度与钙尔奇D片一致。     

利用固体分散体技术改善吴茱萸次碱体外溶出度研究

目的:制备吴茱萸次碱(Rut)固体分散体(SD),提高Rut体外溶出度。方法:分别以聚乙烯吡咯烷酮(PVP)为载体,采用溶剂-共沉淀法,制备含不同辅助载体(微粉硅胶、乳糖、微晶纤维素、去氧胆酸、卵磷脂、滑石粉等)及比例的Rut-SD,评价其体外溶出度并进行处方优选;采用X-射线衍射分析和差示热分析法对SD进行物相鉴别。结果:处方组成以Rut-PVP-微粉硅胶(1∶2∶1)和Rut-PVP-乳糖(1∶2∶2)较好,其累积溶出度(60 min)较同成分组成的物理混合物提高了约6倍;物相鉴别结果表明Rut以微晶状态存在于SD中。结论:以PVP为载体、适当比例的微粉硅胶和乳糖为辅助载体制备的Rut-SD可显著提高Rut的体外溶出度。     

复方碳酸钙颗粒剂人体相对生物利用度

目的 :探讨评价钙制剂体内吸收程度和生物等效性的方法。方法 :18名健康受试者按 3× 3拉丁方随机交叉进行试验。在研究的 3个周期中 ,两周期分别口服 60 0mg复方碳酸钙颗粒剂和钙尔奇D片。每一周期于服药后采集 0～ 1,1～ 2 ,2～ 3 ,3～ 4,4～ 5 ,5～ 6,6～ 8,8～ 10 ,10～ 12 ,12～ 2 4h尿液 ,采用电感耦合等离子体发射光谱法测定尿钙浓度。以给药后 0～2 4h尿钙累积排泄量增量计算相对生物利用度 ,并对主要药动学参数进行方差分析和t检验 ,评价制剂生物等效性。结果 :18名受试者口服复方碳酸钙颗粒剂和钙尔奇D片后 ,相对于空白对照组 ,尿钙累积排泄量增量分别为 ( 3 5 .0± 12 .5 )mg和 ( 3 5 .3± 13 .0 )mg。复方碳酸钙颗粒剂的相对生物利用度为 ( 10 0 .9± 16.2 ) %。结论 :复方碳酸钙颗粒剂和钙尔奇D片体内生物作用等效。     

姜黄素固体分散体的制备和溶出度考察

目的通过姜黄素固体分散体的制备,提高姜黄素的体外溶出度。方法采用溶剂法和熔融法制备固体分散体,考察不同载体的姜黄素固体分散体的性状及体外溶出度实验,筛选并优化处方和工艺。固体分散体的形成通过X-射线衍射及DSC分析证实。结果姜黄素与聚乙烯吡咯烷酮(polyvinyl pyrrolidone,PVP)-K29/32用溶剂法制备的固体分散体的体外溶出最好,最优处方中姜黄素与PVP-K29/32的质量比为1∶6,最优处方中姜黄素在溶出介质人工胃液中30 min累积溶出质量高达98%。结论制备成姜黄素固体分散体可以显著提高姜黄素的体外溶出度。     

固体分散体技术改善吴茱萸次碱溶出特性的研究

目的:制备吴茱萸次碱(Rut)固体分散体,提高Rut体外溶出度.方法:分别以聚乙烯吡咯烷酮(PVP)为载体,采用溶剂-共沉淀法,制备含不同辅助载体的Rut固体分散体;采用差示热分析和X-射线衍射分析对固体分散体进行物相鉴别,并进行体外溶出度试验;考察载体用量、载体中表面活性剂的加入和不同溶出介质对药物溶出特性的影响.结果:Rut以微晶形式存在于固体分散体中;其中,以微粉硅胶和乳糖为辅助载体制备的Rut-PVP-微粉硅胶(1∶2∶1)和Rut-PVP-乳糖(1∶2∶2)固体分散体,其累积溶出度较其物理混合物提高了约6倍.结论:Rut-PVP-微粉硅胶(1∶2∶1)和Rut-PVP-乳糖(1∶2∶2)固体分散体可显著提高药物的溶出速度和程度.     

正交设计优化孟鲁司特钠片的处方工艺

目的:制备孟鲁司特钠片,筛选其最佳处方工艺。方法:采用正交设计法,以与进口孟鲁司特钠片的相似因子f2为指标,对自制孟鲁司特钠片中微晶纤维素与乳糖的比例(A),交联羧甲基纤维素钠(B)、羟丙基纤维素(C)和硬脂酸镁(D)的处方用量百分比进行优选,并进行验证试验。结果:优选所得A、B、C、D分别为41∶45、2.5%、5.5%、0.80%,3批优化处方所制样品f2值均大于50,2种制剂溶出曲线基本相似,30min时累积溶出度均能达到80%以上。结论:自制孟鲁司特钠片处方合理,制备工艺简单易行,体外溶出度良好。     

维A酸固体分散体的制备及其胶囊的溶出度评价

目的:制备维A酸固体分散体,并对其胶囊进行体外溶出度评价。方法:选用聚维酮k30等为辅料,采取溶剂法制备维A酸固体分散体。以体外累积溶出率为指标,在9种不同组成处方中筛选出较佳处方,并进行验证试验。结果:以处方8为较佳处方,所制胶囊体外累积溶出率在45min时均达到95%以上。结论:以聚维酮k30等为辅料可制备溶出度理想的维A酸胶囊。     

碳酸钙分散片的研制

目的研制碳酸钙分散片。方法用正交设计法,以崩解剂羧甲基淀粉钠、溶胀性辅料预胶化淀粉和酸味剂枸橼酸的用量为3因素,在3个水平上拟合,以崩解时限为指标用L9(34)进行实验。并对优选处方制成品进行了溶出度测定。结果优选处方中羧甲基淀粉钠为9%,预胶化淀粉为3%,枸橼酸为8.9%。所研制的碳酸钙分散片崩解时限为53s,3min时钙的累积溶出达98%。结论研制的碳酸钙分散片制备工艺可靠,溶出迅速。     

复方苯巴比妥颗粒的制备

目的：优选复方苯巴比妥颗粒的最佳处方。方法：用正交设计法,以每包颗粒的重量（A）、稀释剂（B）、粘合剂（C）为因素,按L9（3^4）设计实验,以颗粒吸湿性和苯巴比妥溶出度为评价指标,进行综合评分。结果：影响因素顺序为A〉B〉C,其中A、B对颗粒质量影响有显著意义。最佳处方为A1B3C3,即以乳糖为稀释剂、5％的羟丙甲纤维素为粘合剂、每包颗粒重3g。结论：优选的处方、工艺可行,制成的颗粒符合《中国药典》（2005年版）规定。     

复方芍甘颗粒制备工艺的研究

目的：优选复方芍甘颗粒的最佳制备工艺.方法：以颗粒的成型率、吸湿率及有效成分保留率为评价指标,采用正交试验法,对浸膏粉与辅料用量比（A）、混合辅料乳糖与糊精比（B）、乙醇浓度（C）、干燥温度（D）因素进行优化.结果：最佳工艺为A1B1C3D3,即浸膏粉与辅料用量比为1∶1、混合辅料乳糖与糊精比例为1∶1、乙醇浓度为70％、干燥温度为80℃.结论：优选的处方工艺可行,可用于复方芍甘颗粒的生产工艺.     

延胡索乙素贴剂处方研究

目的对延胡索乙素透皮贴剂基质进行优选,确定处方组成。方法以PVA（X1）,PVP（X2）、甘油（X3）、羧甲基纤维素钠（X4）、氮酮（X5）、丙二醇（X6）为因素,用量为水平,采用U6（66）均匀设计,以累积渗透量为考察指标,优选基质。结果透皮贴剂的最优处方比为PVA-PVP-甘油-羧甲基纤维素钠-氮酮-丙二醇=14.44∶5.87∶11.53∶3.00∶4.97∶4.62。结论上述基质处方制备的透皮贴剂的渗透效果较好。     

甘草黄酮胶囊成型工艺的研究

目的确定甘草黄酮胶囊剂成型工艺条件。方法以吸湿率、休止角、堆密度、成型性为筛选指标,确定甘草黄酮胶囊的处方组成;以制剂的外观、性状、崩解时限、含量为评价指标,确定工艺路线。结果甘草黄酮∶预胶化淀粉∶微晶纤维素∶乳糖(27∶4∶7∶2)为最佳处方组成。结论通过质量检测及稳定性实验,证明所确定的工艺路线可行。     

Compressibility and compactibility of granules produced by wet and dry granulation

The bulk properties, compactibility and compressibility of granules produced by wet and dry granulation were compared applying a rotary tablet press, three different morphological forms of calcium carbonate and two particle sizes of sorbitol. Granules from both granulation methods possessed acceptable flow properties; however, the ground (Mikhart) and cubic (Scoralite) calcium carbonate demonstrated better die-filling abilities in the tablet press than the scalenhedral calcium carbonate (Sturcal). The wet processed granules showed in general larger compression properties. This was explained as these granules were mechanical stronger and had a higher initial porosity. In some cases, a large particle surface area of calcium carbonate and sorbitol resulted in a small, insignificant improvement of the consolidation characteristics. A correlation between the compression and compaction characteristics was demonstrated.     

HyperDSC studies of amorphous polyvinylpyrrolidone in a model wet granulation system

Measurements of the properties of amorphous materials are very important to help in the understanding of how materials behave during manufacture, storage and use of medicines. However, there are few methods that are suited to the study of amorphous materials, especially if in multi-component systems or model formulations. The goal here was to explore the potential for the use of HyperDSC to study a model granulation system. It was found that the sensitivity of HyperDSC was such that the glass transition (Tg) of polyvinylpyrrolidone (PVP) could be detected in granules made with realistic levels of this binder. The measured Tg in the granules, even after drying, was very different to that of PVP alone and to PVP in physical mixtures with lactose. It is argued that the granulation process has resulted in the dissolution of some lactose and that the amorphous binder holding the granules together is in fact a solid dispersion of PVP and lactose. Based on the standard Gordon-Taylor equation it was estimated that the solid dispersion contained 50% of PVP and lactose. Given that solid dispersions have a tendency to crystallise on storage, it could be expected that changes in the binder properties will occur with time after granulation. We believe that this is the first measurement of in situ properties of a binder in this way and opens the possibility of studies on formulated systems.     

检测黄热病减毒活疫苗中乳糖和山梨糖醇含量的HPLC的建立

目的  建立检测黄热病减毒活疫苗中乳糖和山梨糖醇含量的高效液相色谱法（high performance liquid chromatography,HPLC）,并验证该法。方法  建立的HPLC的色谱条件确定为：离子排斥色谱柱 Aminex^® HPX-87H （300 mm×7.8 mm）,流动相0.004 mol/L硫酸、流速0.8 ml/min、柱温50 ℃,进样量20 µl。检测该法的系统适用性,并验证该法的线性、准确度、精密度、专属性、稳定性和耐用性。结果  该法的乳糖与山梨糖醇峰间的分离度为6.68,乳糖和山梨糖醇标准曲线的线性良好,线性的决定系数分别为0.999 98和0.999 87。该法的准确度良好,乳糖和山梨糖醇的回收率分别为100.2%～100.4%和101.0%～101.7%,均符合规定的要求。 6次重复检测的乳糖和山梨糖醇结果相对标准偏差分别为0.00%和0.08%;2名分析员于不同时间检测12次的乳糖和山梨糖醇结果相对标准偏差分别为0.30%和0.99%。该法检测乳糖和山梨糖醇质量浓度的定量限分别为0.05 mg/ml和0.06mg/ml。结论  建立的HPLC可用于检测黄热病减毒活疫苗中的乳糖和山梨糖醇含量。     

Elucidation of the internal physical and chemical microstructure of pharmaceutical granules using X-ray micro-computed tomography,Raman microscopy and infrared spectroscopy

X-ray micro-computed tomography (XMCT) was used in conjunction with confocal Raman mapping to measure the intra-granular pore size, binder volumes and to provide spatial and chemical maps of internal granular components in α-lactose monohydrate granules formulated with different molecular weights of polyvinyl pyrrolidone (PVP). Infrared spectroscopy was used to understand the molecular association of binder domains. Granules were prepared by high-shear aqueous granulation from α-lactose monohydrate and PVP K29/32 or K90. XMCT was used to visualise the granule microstructure, intra-granular binder distribution and measure intra-granular porosity, which was subsequently related to intrusion porosimetry measurements. Confocal Raman microscopy and infrared microscopy were employed to investigate the distribution of components within the granule and explore the nature of binder substrate interactions. XMCT data sets of internal granule microstructure provided values of residual porosity in the lactose:PVP K29/32 and lactose:PVP K90 granules of 32.41 ± 4.60% and 22.40 ± 0.03%, respectively. The binder volumes of the lactose:PVP K29/32 and lactose:PVP K90 granules were 2.98 ± 0.10% and 3.38 ± 0.07%, respectively, and were attributed to PVP-rich binder domains within the granule. Confocal Raman microscopy revealed anisotropic domains of PVP between 2 μm and 20 μm in size surrounded by larger particles of lactose, in both granule types. Raman data showed that PVP domains contained various amounts of lactose, whilst IR microscopy determined that the PVP was molecularly associated with lactose, rather than residual water. The work shows that XMCT can be applied to investigate granular microstructure and resolve the porosity and the excipient and binder volumes. Combining this technique with vibrational techniques provides further structural information and aids the interpretations of the XMCT images. When used complementarily, these techniques highlighted that porosity and binder volume were the most significant microstructural differences between the α-lactose monohydrate granules formulated with the different grades of PVP.     

楤木皂苷胶囊成型工艺辅料筛选

目的:优选楤木皂苷胶囊的成型工艺辅料。方法:以颗粒的成型合格率、吸湿百分率、休止角和堆密度为评价指标,在逐一单个筛选辅料的基础上,筛选出适合制备楤木皂苷胶囊的混合辅料,并考察临界相对湿度(CRH)。结果:微晶纤维素-乳糖(1:1,m/m)混合辅料制成的颗粒抗潮性能强,流动性好。CRH为78%。结论:所选辅料可用于制备楤木皂苷胶囊。     

Granule fraction inhomogeneity of calcium carbonate/sorbitol in roller compacted granules

The granule fraction inhomogeneity of roller compacted granules was examined on mixtures of three different morphologic forms of calcium carbonate and three particle sizes of sorbitol. The granule fraction inhomogeneity was determined by the distribution of the calcium carbonate in each of the 10 size fractions between 0 and 2000 microm and by calculating the demixing potential. Significant inhomogeneous occurrence of calcium carbonate in the size fractions was demonstrated, depending mostly on the particles sizes of sorbitol but also on the morphological forms of calcium carbonate. The heterogeneous distribution of calcium carbonate was related to the decrease in compactibility of roller compacted granules in comparison to the ungranulated materials. This phenomenon was explained by a mechanism where fracturing of the ribbon during granulation occurred at the weakest interparticulate bonds (the calcium carbonate: calcium carbonate bonds) and consequently exposed the weakest areas of bond formation on the surface of the granules. Accordingly, the non-uniform allocation of the interparticulate attractive forces in a tablet would cause a lowering of the compactibility. Furthermore, the ability of the powder to agglomerate in the roller compactor was demonstrated to be related to the ability of the powder to be compacted into a tablet, thus the most compactable calcium carbonate and the smallest sized sorbitol improved the homogeneity by decreasing the demixing potential.