Influence of formulation composition and processing on the content uniformity of low-dose tablets manufactured at kilogram scale

The purpose of this study was to investigate the impact of processing, API loading, and formulation composition on the content uniformity of low-dose tablets made using direct compression (DC) and roller compaction (RC) methods at 1?kg scale. Blends of 1:1 microcrystalline cellulose/lactose or 1:1 microcrystalline cellulose/dicalcium phosphate anhydrous with active pharmaceutical ingredient (API) at loadings of 0.2, 1 and 5% were processed either by DC or RC. A statistical analysis showed that DC produced comparable content uniformity results to RC. Microcrystalline cellulose/lactose formulations had improved average potency compared to microcrystalline cellulose/dicalcium phosphate anhydrous formulations for both DC and RC. The impact of segregation in the DC blends and adhesion to equipment surfaces was assessed to aid in understanding potency trends. DC may be as suitable as RC for low-dose regime (e.g. <?1?mg) when manufacturing clinical supplies at small scale provided the API has a suitable particle size and potency loss to equipment is negligible.     

A Generalized Pivotal Quantity Approach to the Parametric Tolerance Interval Test for Dose Content Uniformity Batch Testing

The Food and Drug Administration (FDA) has proposed a parametric tolerance interval test (PTIT) for batch-release testing of inhalation devices. The proposed test examines dose uniformity based on several inhalation units from a batch, with two observations per unit. An underlying assumption is that the observations are a random sample from a univariate normal distribution. Because there are two observations per unit, it may be more appropriate to model the data as stemming from a bivariate normal distribution. We take a bivariate approach and use generalized confidence interval methodology to derive a parametric tolerance interval for the distribution of doses within a batch. We then use Monte Carlo simulation to compare results based on this bivariate approach with those based on the FDA-proposed PTIT.     

"米袋法"在磁共振3D Nerve VIEW臂丛神经根成像中的应用

目的 探讨"米袋法"在磁共振3D Nerve VIEW臂丛神经根检查中的应用.方法 使用3.0T MR对22名健康志愿者和28名臂丛损伤患者采用3D Nerve VIEW进行MR臂丛神经检查,均分别进行常规和加用米袋两次扫描,对健康志愿者和患者的磁共振图像进行分析.测量比较健康志愿者加米袋前后臂丛神经节的图像信噪比(signal to noise ratio,SNR)和对比噪声比(contrast to noise ratio,CNR);采用4分法对臂丛显示情况进行主观评分,对成像质量的差异性进行统计学分析.根据臂丛损伤患者术中探查结果,计算加米袋前后臂丛损伤的检出率.结果 加米袋前臂丛神经SNR为1.90±0.66,CNR为14.27±6.82,加米袋后SNR为2.70±0.88,CNR为20.00±6.83,两者有显著差异(P<0.05).主观评分由2.45±0.64提高到3.96±0.95,P<0.05.臂丛损伤患者加用米袋后臂丛神经损伤诊断的检出准确率由69.7％ 提高至81.8％.结论 "米袋法"可在臂丛神经根成像中显著提高SNR、CNR,提高臂丛神经成像质量,提高臂丛损伤的检出率,有较好的临床应用价值.     

家兔脑出血模型头颅CT值变化规律初步探讨

目的:通过立体定向技术注射家兔自体动脉血到达脑基底节区的方法,构建家兔脑出血模型,分析不同时间段注射血液后头颅CT值的演变规律,探讨脑出血后头颅CT混合征形成的可能机制。方法:健康家兔70只,根据注入脑组织血液成分的不同分为全血组(50只)、血浆组(10只)和血清组(10只);对于全血组,根据注血间隔时间的不同又分为5个亚组,分别为A亚组(间隔1 h)、B亚组(间隔2 h)、C亚组(间隔3 h)、D亚组(间隔4 h)、E亚组(间隔5 h),每组10只,首次注射自体动脉血形成血肿后分别在不同时间段内再次注射相同成分的血液到血肿周边形成二次血肿;对于血清组和血浆组,于注射全血形成血肿后同时间段内向血肿周边或对侧分别注射自体血血清或血浆,造模完成后立即行头颅CT,记录家兔头颅CT不同区域的CT值,对比注射不同血液成分CT值的变化和同一血液成分间隔不同时间CT值的变化规律。结果:全血组经不同时间段向颅内注血可形成高低不同密度的血肿病灶,其低密度部位CT值高于脑组织与脑脊液,类似混合征表现;血清和血浆组亦可形成高低密度,但低密度部位与脑脊液CT值相近,不易区分,不符合混合征征象。结论:二次出血可能是脑出血头颅CT混合征的形成原因,而低密度区可能是首发出血,高密度区则可能是新发出血。     

GC法测定胃痛宁片小茴香油的含量均匀度

摘 要 目的： 建立胃痛宁片中小茴香油含量均匀度的测定方法,考察胃痛宁片中小茴香油的含量均匀度。方法: 以水杨酸甲酯为内标,采用GC法测定样品中小茴香油主成分反式茴香脑的含量。色谱条件：DB FFAP毛细管柱（30 m×0.32 mm,0.25 μm）;柱温:145℃;进样口温度：180℃;FID检测器温度:230℃;载气为高纯氮,体积流量:0.8 ml·min^-1,空气体积流量:400 ml·min^-1,氢气体积流量:35 ml·min^-1。对GC法进行方法学考察,并比较不同厂家及同一厂家不同批号胃痛宁片小茴香油的含量均匀度。结果: 小茴香油中主要成分反式茴香脑在2.189～35.030 μg·ml^-1（r=0.999 9)浓度范围内呈良好的线性关系,平均回收率为100.06%,RSD为0.5%(n=9)。不同生产厂家的胃痛宁片以及同一厂家不同批号胃痛宁片中小茴香油含量均匀度均有明显差异。结论:该方法简便快捷,能准确测定该药品的含量均匀度,可用于该制剂的质量控制。     

低压下加肥对迷宫滴头流量及灌水均匀度的影响--测试文章

针对滴灌中侧翼迷宫式滴灌带的流量、灌水均匀度、肥料堵塞等问题,对4种不同规格的侧翼迷宫滴灌带进行试验,测定在清水和加肥灌水时滴头的流量及灌水均匀度。结果表明：加肥灌水时滴头流量比清水时减少,灌水均匀系数也较清水减小,4种不同结构滴头的灌水均匀度系数减小了5%～9.9%;随着灌水间隔增长,灌水次数增加,由于溶解在水中化学肥料结晶析出造成的堵塞程度逐渐增加;迷宫流道结构不同滴头的化学堵塞程度也不同。     

纤维素-热塑性聚氨酯共混膜的制备及性能

利用乙二胺活化纤维素,将活化后的纤维素（Ce）和热塑性聚氨酯（TPU）分别溶于氯化锂（LiCl）-N,N-二甲基乙酰胺（DMAC）体系,制得纤维素-热塑性聚氨酯（Ce-TPU）共混膜。利用傅里叶红外光谱仪（FT-IR）、扫描电子显微镜（SEM）、X射线衍射仪（XRD）、单纤强力仪、折痕恢复性测定仪对共混膜的结构和性能进行表征。结果表明：Ce和TPU相容性良好,w(TPU)=30%时为共混膜的最优配比,此时断裂强力较纯纤维素膜略有提高,断裂伸长率提高了68%,折皱回复角提高了17%,共混膜的抗皱性和弹性有所改善。     

Properties of the ON bistratified ganglion cell in the rabbit retina

The identity of the types of different neurons in mammalian retinae is now close to being completely known for a few mammalian species; comparison reveals strong homologies for many neurons across the order. Still, there remain some cell types rarely encountered and inadequately described, despite not being rare in relative frequency. Here we describe in detail an additional ganglion cell type in rabbit that is bistratified with dendrites in both sublaminae, yet spikes only at light onset and has no response bias to the direction of moving bars. This ON bistratified ganglion cell type is most easily distinguished by the unusual behavior of its dendritic arbors. While dendrites that arborize in sublamina b terminate at that level, those that ascend to arborize in sublamina a do not normally terminate there. Instead, when they reach the approximate radius of the dendrites in sublamina b, they dive sharply back down to ramify in sublamina b. Here they continue to course even further away from the soma at the same level as the branches wholly contained in sublamina b, thereby forming an annulus of secondary ON dendrites in sublamina b. This pattern of branching creates a bistratified dendritic field of approximately equal area in the two sublaminae initially, to which is then added an external annulus of dendrites only in sublamina b whose origin is entirely from processes descending from sublamina a. It is coupled to a population of wide‐field amacrine cells upon which the dendrites of the ganglion cell often terminate. J. Comp. Neurol. 521:1497–1509, 2013. © 2012 Wiley Periodicals, Inc.     

Impact of Superdisintegrants and Film Thickness on Disintegration Time of Strip Films Loaded With Poorly Water-Soluble Drug Microparticles

Although strip films are a promising platform for delivery of poorly water-soluble drug particles via slurry casting, the effect of critical material attributes, for example, superdisintegrants (SDIs) on critical quality attributes, including film disintegration time (DT), remains underexplored. A 2-level factorial design is considered to examine the impact of the SDI type (sodium starch glycolate and croscarmellose sodium), their amount, and film thickness. SDIs were used with hydroxypropyl methylcellulose (E15LV) and glycerin solutions along with viscosity matching. Fenofibrate, a model poorly water-soluble drug, was micronized and surface modified via fluid energy milling. Significant decreases in film DT, measured using 3 different methods, were observed due to the addition of SDIs. Percentage reduction in DT was a strong function of SDI amount, and thinner films disintegrated faster. Films with either higher SDI concentrations (>9%) or films under 80 μm, exhibited fast DT (<180 s, European Pharmacopeia). All thin films (50-60 μm) exhibited immediate release (>80% in 10 min). All films achieved good content uniformity, except for those with the lowest amount of SDI, attributed to insufficient viscosity and thickness nonuniformity due to the SDI. Finally, all films achieved adequate mechanical properties, notwithstanding minor negative impact of SDIs.     

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.