Exploration of statistical dependence between illness parameters using the entropy correlation coefficient

The entropy correlation coefficient (ECC) is a useful tool for measuring statistical dependence between variables. We employed this tool to search for pairs of variables that correlated in the chronic fatigue syndrome (CFS) Computational Challenge dataset. Highly related variables are candidates for data reduction, and novel relationships could lead to hypotheses regarding the pathogenesis of CFS. METHODS: Data for 130 female participants in the Wichita (KS, USA) clinical study [1] was coded into numerical values. Metric data was grouped using Gaussian mixture models; the number of groups was chosen using Bayesian information content. The pair-wise correlation between all variables was computed using the ECC. Significance was estimated from 1000 iterations of a permutation test and a threshold of 0.01 was used to identify significantly correlated variables. RESULTS: The five dimensions of multidimensional fatigue inventory (MFI) were all highly correlated with each other. Seven Short Form (SF)-36 measures, four CFS case-defining symptoms and the Zung self-rating depression scale all correlated with all MFI dimensions. No physiological variables correlate with more than one MFI dimension. MFI, SF-36, CDC symptom inventory, the Zung self-rating depression scale and three Cambridge Neuropsychological Test Automated Battery (CANTAB) measures are highly correlated with CFS disease status. DISCUSSION: Correlations between the five dimensions of MFI are expected since they are measured from the same instrument. The relationship between MFI and Zung depression index has been previously reported. MFI, SF-36, and Centers for Disease Control and Prevention (CDC) symptom inventory are used to classify CFS; it is not surprising that they are correlated with disease status. Only one of the three CANTAB measures that correlate with disease status has been previously found, indicating the ECC identifies relationships not found with other statistical tools. CONCLUSION: The ECC is a useful tool for measuring statistical dependence between variables in clinical and laboratory datasets. The ECC needs to be further studied to gain a better understanding of its meaning for clinical data.     

Lack of correlation between lithium pharmacokinetic parameters obtained from plasma and saliva

One tablet containing 755 mg of lithium tryptophanate (10.8 mEq of lithium) was administered to eight healthy volunteers. The main pharmacokinetic parameters for the group of subjects were estimated. Pharmacokinetic parameters (mean +/- SD) from plasma and saliva were respectively: half life (t1/2) 17 +/- 6 vs. 21.8 +/- 14 h; mean residence time 23.7 +/- 7.4 vs. 24.4 +/- 15.3 h; total clearance 30.6 +/- 9.3 vs. 28.6 +/- 6.2 ml/h/kg; and apparent volume of distribution 0.71 +/- 0.20 vs. 0.84 +/- 0.37 L/kg. Although the mean pharmacokinetic parameters in plasma and saliva were similar, there was no significant correlation between the calculated parameters in the individual subject (p greater than 0.05). The usefulness of monitoring salivary levels of lithium is questionable.     

Physicochemical parameters in biological correlation analysis: meaning and limits

Correlation analysis assumes that the physicochemical factors governing the transport, metabolism and drug-receptor interaction can be factored into hydrophobic-lipophilic component, polarizability and dispersion forces, electronic and steric effects and into indeterminate factors. Using computerized regression analysis, a generalized equation can be formulated to correlate the biological response of a set of compounds with their chemical structures in terms of physicochemical parameters of substituents. In order to explore the scope of each defined physicochemical parameter, correlations between biological effects and some combination of substituent indices are discussed.     

The effects of alginate molecular structure and formulation variables on the physical characteristics of alginate raft systems

A study has been conducted in order to assess the effects of alginate molecular structure and formulation variables on alginate raft strength and dimensions. In addition, the use of texture analysis as a novel means of characterising alginate raft systems has been investigated. Five alginates of known molecular composition were used (LFR 5/60, LF 120M, LF 10/40RB, LF 20/200 and LF 200DL), while two gas-forming agents (sodium and potassium bicarbonate) and two divalent cationic salts (calcium carbonate and zinc carbonate) were studied. The effects of acid strength on raft formation was also investigated. It was noted that the inclusion of divalent cations and the use of the lowest molecular weight alginate sample (LFR 5/60) increased the volume of the resulting rafts. Texture analysis measurements allowed both the maximum breaking strength and the work involved during the rupture process to be quantified. Inclusion of divalent cations (particularly calcium) increased the raft strength, while inclusion of potassium carbonate resulted in stronger rafts than did sodium carbonate. Alginates with higher guluronic acid contents resulted in stronger rafts, with the exception of LFR 5/60 which yielded weaker rafts despite the high G ratio, probably as a result of the lower molecular weight of this material. Raft volume and strength increased with decreasing pH of the raft forming media.     

Fabrication of microparticle protein delivery systems based on calcium alginate

Microparticle protein delivery systems based on calcium alginate were fabricated using a very convenient method, i.e. directly shredding the protein-loaded calcium alginate beads into microparticles in a commercial food processor for 3 min. Bovine serum albumin (BSA) as a model protein was encapsulated in the calcium alginate microparticles. The obtained protein-loaded microparticles were then coated with chitosan. This fabrication method offered high encapsulation efficiency and a high particle yield. Compared with beads, the microparticles exhibited a faster release rate in the initial release stage. By comparing the release profiles of uncoated beads/microparticles and chitosan-coated beads/microparticles, it was found that the releases from chitosan-coated beads/microparticles were slower. To examine whether the loaded protein denatured during the microparticle fabrication, trypsin was encapsulated in the calcium alginate microparticles and the bioactivity of trypsin released from the microparticles was measured.     

Chemical and technological delivery systems for idebenone: a review of literature production

Introduction: Idebenone (IDE) is an antioxidant compound, structurally related to coenzyme Q10. Its therapeutic potential is growing in different application areas, as demonstrated by the number of experimental works and patents produced in very recent years.

Areas covered: Cyclodextrin inclusion complexes, liposomes, microemulsions, prodrugs, polymeric and lipid nanoparticles have been explored to achieve different goals, such as topical administration, brain targeting or increasing the bioavailability of this highly lipophilic drug. This review summarizes the results of works published in the last 20 years for the delivery and targeting of this drug.

Expert opinion: A direct comparison of the different carrier systems is not easy and could not even be significant, due to the large variables existing among them. However, the different forms of delivery can help increase idebenone solubility, stability and biochemical activity. Further studies will be developed in order to improve the controlled release and targeting of idebenone.     

Application of chitosan/alginate nanoparticle in oral drug delivery systems: prospects and challenges

Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g. ulcerative colitis and colorectal cancer), as they improve therapeutic efficiency and reduce systemic toxicity. Chitosan/alginate nanoparticles (CANPs) show strong electrostatic interaction between the carboxyl group of alginates and the amino group of chitosan which leads to shrinkage and gel formation at low pH, thereby protecting the drugs from the gastrointestinal tract (GIT) and aggressive gastric environment. Meanwhile, CANPs as biocompatible polymer, show intestinal mucosal adhesion, which could extend the retention time of drugs on inflammatory sites. Recently, CANPs have attracted increasing interest as colon-targeted oral drug delivery system for intestinal diseases. The purpose of this review is to summarize the application and treatment of CANPs in intestinal diseases and insulin delivery. And then provide a future perspective of the potential and development direction of CANPs as colon-targeted ODDSs.     

TEG参数与急性脑梗死患者病情进展的关系分析

目的 探讨血栓弹力图(TEG)参数与急性脑梗死患者病情进展的关系.方法 选择106例急性脑梗死患者作为观察组,按照美国国立卫生研究院卒中量表(NIHSS)评分将患者分成轻度组(NIHSS评分<6分,44例)、中度组(NIHSS评分6～16分,32例)、重度组(NIHSS评分>16分,30例);并选取同期46例健康者作为...     

Production of BSA-loaded alginate microcapsules: Influence of spray dryer parameters on the microcapsule characteristics and BSA release

The aim of this study was to optimize the production of BSA-loaded alginate microcapsules by spray drying and to study the release of bovine serum albumin fraction V (BSA) under gastric simulated conditions. Microcapsule yield, BSA release, microcapsule size and size distribution were characterized following the application of different production parameters including inlet air temperature, inlet air pressure and liquid feed rate. The microcapsules were incubated in 0.1?N HCl and BSA release was quantified over time. The yields were higher with the pressure of 3?bar compared to 4?bar and with a feed rate of 0.45 vs. 0.2?ml s^?1. A high feed rate (0.45 vs. 0.2?ml s^?1) allows one to obtain microcapsules with a low BSA release (p?=?0.0327). The increase of the atomizer inlet temperature leads to microcapsules with a higher BSA release (p?=?0.0230). A higher air pressure of 4?bar compared to 3?bar resulted in a lower microcapsule size (2.55 vs. 2.80?µm) and led to a narrower size distribution (0.92 vs. 1.07). In conclusion, the spray dryer parameters influenced the alginate microcapsule characteristics as well as subsequent protein release into a simulated gastric medium.     

Production of BSA-loaded alginate microcapsules: influence of spray dryer parameters on the microcapsule characteristics and BSA release

The aim of this study was to optimize the production of BSA-loaded alginate microcapsules by spray drying and to study the release of bovine serum albumin fraction V (BSA) under gastric simulated conditions. Microcapsule yield, BSA release, microcapsule size and size distribution were characterized following the application of different production parameters including inlet air temperature, inlet air pressure and liquid feed rate. The microcapsules were incubated in 0.1 N HCl and BSA release was quantified over time. The yields were higher with the pressure of 3 bar compared to 4 bar and with a feed rate of 0.45 vs. 0.2 ml s(-1). A high feed rate (0.45 vs. 0.2 ml s(-1)) allows one to obtain microcapsules with a low BSA release (p = 0.0327). The increase of the atomizer inlet temperature leads to microcapsules with a higher BSA release (p = 0.0230). A higher air pressure of 4 bar compared to 3 bar resulted in a lower microcapsule size (2.55 vs. 2.80 microm) and led to a narrower size distribution (0.92 vs. 1.07). In conclusion, the spray dryer parameters influenced the alginate microcapsule characteristics as well as subsequent protein release into a simulated gastric medium.     

Production of BSA-loaded alginate microcapsules: Influence of spray dryer parameters on the microcapsule characteristics and BSA release

The aim of this study was to optimize the production of BSA-loaded alginate microcapsules by spray drying and to study the release of bovine serum albumin fraction V (BSA) under gastric simulated conditions. Microcapsule yield, BSA release, microcapsule size and size distribution were characterized following the application of different production parameters including inlet air temperature, inlet air pressure and liquid feed rate. The microcapsules were incubated in 0.1?N HCl and BSA release was quantified over time. The yields were higher with the pressure of 3?bar compared to 4?bar and with a feed rate of 0.45 vs. 0.2?ml?s^?1. A high feed rate (0.45 vs. 0.2?ml?s^?1) allows one to obtain microcapsules with a low BSA release (p?=?0.0327). The increase of the atomizer inlet temperature leads to microcapsules with a higher BSA release (p?=?0.0230). A higher air pressure of 4?bar compared to 3?bar resulted in a lower microcapsule size (2.55 vs. 2.80?µm) and led to a narrower size distribution (0.92 vs. 1.07). In conclusion, the spray dryer parameters influenced the alginate microcapsule characteristics as well as subsequent protein release into a simulated gastric medium.     

硅橡胶质量参数与氟尿嘧啶植入剂释放度的相关性研究

目的 分析硅橡胶分子量及黏度特性对氟尿嘧啶植入剂释放度的影响。方法 依据GN/T21863-2008标准和《中国药典》对不同批号硅橡胶的分子量分布和黏度进行检测,记录数均分子量、分子量分布和黏度,采用相同制剂工艺制备20份不同硅橡胶的小试样品,依据国家药品标准WS1-（X-103）-2005Z对小试样品的释放度进行检测,以数均分子量（X₁）、分子量分布（X₂）和黏度（X₃）作为X变量,以120 h释放度结果作为Y变量,使用Minitab 16.0软件进行多元回归分析,确定硅橡胶关键质量参数。结果 多元回归分析表明,数均分子量和黏度参数是关键质量参数（P<0.05）,分子量分布为非关键质量参数（P>0.05）;120 h释放度的线性回归方程：Y=-0.3+3.76 X₁+0.267X₃。结论 硅橡胶数均分子量和黏度是影响氟尿嘧啶植入剂释放度的关键质量参数,产品生产过程中应依据制剂工艺参数对硅橡胶的制备进行严格控制,从而最大程度降低硅橡胶对产品质量稳定性造成的影响。     

Sustained release of antineoplastic drugs from chitosan-reinforced alginate microparticle drug delivery systems

Alginate based microparticle drug delivery systems were prepared for the sustained release of antineoplastic drugs. Two drugs, 5-fluorouracil (5-FU) and tegafur, were encapsulated into the microparticles. The drug loaded microparticles were fabricated using a very convenient method under very mild conditions, i.e., directly shredding the drug loaded beads into microparticles in a commercial food processor. The mean sizes of the obtained microparticles were between 100 and 200 μm. To effectively sustain the drug release, alginate microparticles were reinforced by chitosan during gelation. The drug release from the chitosan-reinforced alginate microparticles was obviously slower than that from the unreinforced microparticles. The effect of the reinforcement conditions on the drug release property of the microparticles was studied, and the optimized concentration of chitosan solution for reinforcement was identified. The effects of drug feeding concentration and pH value of the release medium on the drug release were investigated.     

Clinical trials: relevance of correlation between treatment responses

Objective: Trials that do not allow rejection of the null hypothesis of no treatment effect may have had an inappropriate design. Trials are virtually never assessed for correlation between responses to different treatment modalities. Methods: Using a hypothetical example and several published studies we examine the influence of correlation levels between treatment modalities on the sensitivity of testing. Results: The level of correlation between responses to different treatment modalities is a major determinant of the sensitivity both of crossover and parallel group clinical trials. Conclusions: It is very relevant to assess a priori correlation levels between responses to the different treatment modalities of a trial. If a negative correlation is anticipated, a crossover design is likely to lack sensitivity. If a positive correlation is anticipated a parallel-group design seems less appropriate, because it would lack the extra sensitivity of accounting for the positive correlation. Both designs would seem suitable for approximately zero correlations (e.g. comparison vs baseline or vs placebo under the assumption that the number of placebo responders is negligible). Received: 10 July 1995/Accepted in revised form: 6 September 1995     

阻塞性睡眠呼吸暂停综合征患者炎症细胞水平与睡眠呼吸监测参数的相关性分析

目的分析阻塞性睡眠呼吸暂停综合征(OSAS)患者炎症细胞水平与睡眠呼吸监测参数的相关性。方法 114例OSAS患者根据睡眠呼吸暂停低通气指数(AHI)分为轻度(16例)、中度(29例)和重度(69例)三组;另选取60例健康体检者作为对照组。比较各组白细胞、淋巴细胞、单核细胞、中性粒细胞、嗜酸性粒细胞及嗜碱性粒细胞计数,并分析睡眠呼吸监测指标与炎症细胞水平的相关性。结果四组间的白细胞计数、单核细胞计数、中性粒细胞计数差异有统计学意义(P<0.05);与对照组相比,重度组白细胞计数、中性粒细胞计数增加(P<0.05);与轻-中度组相比,重度组单核细胞计数、嗜酸性粒细胞计数增加(P<0.05)。OSAS患者AHI与最低血氧饱和度呈负相关(r=-0.660,P<0.05),而与氧饱和度<90%的时间、氧减指数、白细胞计数、单核细胞计数、中性粒细胞计数均呈正相关(r=0.755、0.885、0.206、0.213、0.200,P<0.05);最低血氧饱和度与白细胞计数、中性粒细胞计数呈负相关(r=-0.162、-0.177,P<0.05)。结论重度OSA...     

The influence of technological parameters on the physicochemical properties of blank PLGA nanoparticles

In this work, PLGA nanoparticles were prepared by an emulsification-diffusion technique. The main objective was to optimize the preparation of formulations by evaluating the influence of the technological parameters on the physicochemical properties of PLGA nanoparticles. The effects of variations in polymer and emulsifier concentrations, and homogenization duration, rate and type on the particle size distribution, surface charge and morphology of nanoparticles were assessed. The smallest nanoparticles (177.53 +/- 2.78 nm) were obtained with a 2% PLGA (w/v) concentration in the organic phase and 3% PVA (w/v) in the aqueous phase and were prepared by an emulsification-diffusion method via ultrasonic homogenization at a power of 80 W applied for 30 s. It was observed that nanoparticles prepared by Ultra Turrax were more spherical but larger. In addition, increasing the PVA concentration in the aqueous phase, increasing the PLGA concentration in the organic phase and increasing the homogenization rate decreased the zeta potential values of PLGA nanoparticles.     

Rheological characterization and turbidity of riboflavin-photosensitized changes in alginate/GDL systems.

Riboflavin (RF) in combination with light, in the wavelength range of 310-800 nm, is used to induce degradation of alginic acid gels. Light irradiation of alginate solutions in the presence of RF under aerobic conditions causes scission of the polymer chains. In the development process of a new drug delivery system, RF photosensitized degradation of alginic acid gels is studied by monitoring changes in the turbidity and rheological parameters of alginate/glucono-delta-lactone (GDL) systems with different concentrations of GDL. Addition of GDL induces gel formation of the samples by gradually lowering the pH-value of the system. The turbidity is measured and the cloud point determined. The turbidity starts to increase after shorter times with enhanced concentration of GDL. Enhanced viscoelasticity is detected with increasing GDL concentration in the post-gel regime, but small differences are detected at the gel point. The incipient gel is 'soft' and has an open structure independent on the GDL concentration. In the post-gel regime solid-like behavior is observed, this is more distinct for the systems with high GDL concentrations. The effect of photosensitized RF on alginate/GDL systems decreases with increasing amount of GDL in the system. The same trend is detected whether the systems are irradiated in the pre-gel or in the post-gel regime.     

Industrial perspective of gastroretentive drug delivery systems: physicochemical, biopharmaceutical, technological and regulatory consideration

INTRODUCTION: Gastroretentive drug delivery systems (GRDDS) can overcome drawbacks associated with oral drug delivery, by defeating natural physiological principles. Various gastroretentive technologies have been developed in the past, but few of them achieved success on the market. AREAS COVERED: This review is focused on the key concepts required to make a high-quality drug product available in a timely and economical manner. EXPERT OPINION: Pharmacotherapy of various disease states can be amended by drug repurposing through GRDDS. Assessment of the effect of the fed and fasted condition on product performance should be necessary during initial development phases. Dual working technology would be a possible way to overcome drawbacks associated with different GRDDS. Before development of a drug product, the principles of scale up and process validation must be considered to improve the quality and market availability of GRDDS. Knowledge of all regulatory aspects will help to deliver a product to the market within a reasonable timeframe and in a cost-effective manner.