正交设计法在药物制剂研究中的应用进展

正交设计法(orthogonal design)是一种研究与处理多因素实验的重要数理统计方法,它按照数理统计提供的一系列规格化的正交表来安排试验,以尽可能少的试验次数,获得最满意的试验结果。正交表是合理安排试验和数据分析的主要工具,正交试验的设计主要通过正交表进行。正交表有下述     

应用Excel表格建立正交试验自动数据处理系统

目的:建立方便快捷的正交试验数据自动处理系统.方法:分析正交试验原始数据与最终结果之间内在的函数关系,应用Office的组件之一Excel中强大的函数功能建立自动数据处理系统.结果:建成了一套系统的正交试验数据自动处理表格,只需输入试验的原始数据,便可立即得到所需的正交试验结果.结论:应用Excel强大的计算功能处理烦琐的正交试验数据准确、方便、快捷.     

正交设计法在制剂研究中的应用进展

正交设计法(orthogonaldesign)是一种研究与处理多因素实验的重要数理统计方法,它按照数理统计提供的一系列规格化的正交表来安排试验,以尽可能少的试验次数,获得最满意的试验结果。正交表是合理安排试验和数据分析的主要工具,正交试验的设计主要通过正交表进行。正交表有下述性质[1]:正交性,均衡分散性,齐同可比性,可用于分析交互作用。正交试验的成功与失败,很大程度取决于正交表的选择,一般应考虑因素、水平、实验次数、是否重复以及统计分析方法。研究者可将上述五方面条件进行综合考虑,从而选择最佳正交表。药物制剂品种繁多,剂型全面,…     

无空列正交试验的设计及SPSS软件的数据处理

初步介绍了无空列正交试验的设计原理,并利用SPSS软件进行方差分析,使正交试验能更广泛地运用于药学、药理学试验设计,提高试验的科学性。     

Excel在L_9(3~4)正交试验数据处理改进中的应用

目的:完善L9(34)正交试验数据处理。方法:利用抛物线拟合对符合要求的3点数据进行优化,应用Excel自动计算功能编制算法程序,制成模板保存。结果与结论:L9(34)正交试验数据处理经改进更为完善,改进取得成功,优化结果优于原正交试验数据处理结果。Excel操作简单,功能强大,数据分析精确,可作为L9(34)正交试验数据处理的理想手段。     

2000～2009年我国优秀硕士论文中药物正交试验的统计分析

目的:分析我国药物研究方面硕士研究生对正交试验设计的使用情况与特点.方法:以中国知网中药物研究的优秀硕士论文为材料,对正交试验使用的频次、各类药物中的分布、所涉及的院校、学科、专业、研究内容、正交试验设计表的类别、结果处理等数据进行统计分析.结果:正交试验设计在药物研究的优秀硕士论文中于2000年开始出现,总体呈增加趋...     

正交设计法在药物制剂研究中的应用

正交设计法能使药物制剂研究尽可能减少试验次数，正交表是合理安排试验和数据分析的主要工具，由此可获得满意的试验结果。     

正交设计法在胃膜素、胃蛋白酶联产工艺中提高得率、效价的初步应用

<正> 一、前言: 在生产斗争和科学实验中,为了不断提高产品质量与数量,经常会遇到多因子多指标试验问题。正交设计法(又称正交试验法或正交试验设计法),它同“优选法”一样,是用数学原理合理按排试验,以求用较少的试验次数较快     

在正交试验设计中SAS编程处理的应用

目的：为方便广大医药工作者对正交试验数据的统计分析处理，初步掌握常用的一些正交试验数据处理的编程知识。方法：使用SAS6．12统计软件，列举常用的一些正交试验数据编程处理的程序，并将其结果与用其他统计软件的处理结果进行对比。结果：对于相同的正交试验数据，用SAS编程处理相对要简单，明了，易于套用；且分析结果与其他统计软件的分析结果相同。结论：利用SAS编程进行药学研究中的正交试验数据的分析处理，可使十分繁杂的数据处理工作快速、简单、可行。     

正交试验优化飞燕草总黄酮提取工艺

目的：优选飞燕草总黄酮最佳提取工艺。方法：采用正交试验优化飞燕草乙醇提取工艺条件,并利用紫外分光光度法测定总黄酮含量。结果：正交试验确定最优提取条件,80%乙醇提取3次,每次1.5h,乙醇用量为10倍药材量。结论：该正交试验优化工艺简便、可行、重现性好。     

Evaluation of the effect of food on the pharmacokinetics of avitriptan

Bioavailability of avitriptan was found to decrease significantly when administered 5 min after a standard high fat meal. The studies described herein were carried out to gain insight into the mechanism of this food effect. A series of studies were conducted in humans to assess the effect of timing of meal, type of meal, gastric pH, change in the formulation and dose on the bioavailability of avitriptan. Avitriptan was administered as a 50 mg capsule under fasted condition and at 30 min, 1, 2 and 4 h after a standard high fat meal. The reduction in avitriptan bioavailability persisted even at 4 h post high fat meal, although as the time interval between the meal and dose increased, the effect of meal tended to decrease. Bioavailability of avitriptan also decreased significantly when the drug was administered after a high protein and a high carbohydrate meal. Elevation in gastric pH caused by food was not found to be responsible for the food-related decrease in bioavailability of avitriptan since ranitidine pretreatment did not lead to a decrease in bioavailability. When administered as a 50 mg ¹⁴C-labeled solution after a standard high fat meal, bioavailability of avitriptan decreased although the decrease was less compared with that observed for a capsule dosage form. Plasma concentrations and cumulative urinary excretion of total radioactivity also decreased in the fed condition, indicating the absorption of avitriptan was affected. The decrease in avitriptan AUC was somewhat more pronounced than the decrease in the exposure to the total radioactivity suggesting a food-related increase in the first-pass metabolism of avitriptan. Effect of the standard high fat meal on avitriptan administered as a 150 mg capsule was similar to that observed at the 50 mg dose. Overall, the results indicate that bioavailability of avitriptan is significantly reduced irrespective of the type of meal, dose and dosage form and the effect persists for as long as 4 h post meal. Thus, it appears that avitriptan absorption and bioavailability are highly sensitive to presence of food in the stomach and any food-related changes in gastric emptying time and gastrointestinal motility. © 1998 John Wiley & Sons, Ltd.     

泽泻功效的方药考辨

泽泻在《神农本草经》中有补益之功,然而《药典》中并无此记载。通过查阅古籍中相关文献对泽泻的功效进行考证,结果发现宋代之前泽泻功效有补益、利水、泄热,从宋代开始,部分医家对泽泻补益的观点提出质疑,明代医家则认为泽泻补益之功源自利水之效,并不能直接补益,清代医家认为泽泻的核心功效为利水,补益是对泽泻功效的过度赞美,无实际临床意义,至此,泽泻补益的说法完全退出主流中医理论的历史舞台。此外,还发现泽泻止泄精的功效历代医籍中均有文献佐证,然而药典中并无此记载。     

Thresholds of carcinogenicity of flavors.

Fifteen compounds approved by the FEMA (Flavor and Extract Manufacturers Association) expert panel as GRAS (Generally Recognized As Safe) and structurally related compounds have been reported to be carcinogenic in rodent studies. The dose response of the 15 compounds in these studies was scrutinized by attempting to plot the percentage of animals with tumors against the dose of the compound on a logarithmic scale in molecules of compound per kg per day (the Rozman scale). Four compounds had either no or an inverse dose response: benzaldehyde, furfural, 3,4-dihydroxycoumarin, and gamma-buterolactone. Three had a response at one dose only: anethole, estragole (2 studies), and isophorone. Obviously, a dose-response curve could not be generated for these 7 compounds. Four compounds had an increasing response at two doses (benzyl acetate, cinnamyl anthranilate, ethyl acrylate, and estragole); three compounds had increasing responses at three doses (citral, 2,4-hexadienal, and pyridine); one compound had increasing responses at four doses (methyl eugenol). The three compounds with three doses fit a linear plot with a correlation coefficient of at least 0.9; the four doses in male rats of methyl eugenol fit a linear plot with a correlation coefficient of 0.999983. The intercept at zero percentage tumors of these linear fits was at least several orders of magnitude greater than the estimated daily dose of these flavoring agents to individuals in the United States. This is interpreted to indicate that these flavoring agents have a clear threshold for carcinogenicity in animals that is well above the levels currently approved for use in foods; consequently, these animal studies should not be a cause for concern for carcinogenicity of these compounds in humans. Rather, the animal studies should be viewed as providing evidence for the safety of these compounds at current levels of human exposure.     

The measurement of situational influences of smoking

Two experiments were conducted to examine procedures for assessing the relationships between various environmental stimuli and smoking. Fourteen students not desiring to quit smoking, who smoked more than 10 cigarettes per day, were recruited in Experiment I to participate in a study to monitor smoking and were instructed to smoke normally during the measurement period. Situations in which smoking occured were rated on a smoking questionnaire and continuously monitored by self-monitoring techniques. Correlational procedures indicated a high test-retest reliability over a two week period for repeated presentation of the smoking questionnaire, with low to moderate relationships between the scale and the self-monitored smoking behavior. Analysis of the self-monitoring records indicated consistent relationships between smoking and temporal variables, and moderate relationships with environmental events. No significant changes in smoking rates were found as a function of self-monitoring. In Experiment II, the self-monitoring procedures used in Experiment I were evaluated in terms of possible controlling effects and measurement reliability. Nine students were recruited and instructed not to change their smoking behavior. No significant changes in smoking rates were found as a function of self-monitoring. Percent agreement reliability between the smoker and a participant observer in the natural environment indicated smoking could be self-monitored reliably.     

Reversibility of the Effects of Cyclophosphamide on Collagen: Biochemical Studies on Skin and Granulation Tissue and Determination of Thermal Stability of Tail Tendons of Rats

Abstract Granulation tissue was produced in rats by subcutaneous implantation of viscose cellulose sponges. Treatment with cyclophosphamide in a dose of 10 mg/kg/day for 14 days caused an increase in acid soluble OH-proline and a decrease in alpha/beta ratio of acid soluble collagen of granulation tissue. Forty-two days of continuous cyclophosphamide treatment caused a decrease in dry weight, in free OH-proline, and in salt soluble OH-proline in granulation tissue. These findings are in accordance with previous observations of a decreased collagen synthesis and an inhibited collagen degradation in granulation tissue after cyclophosphamide treatment. In skin, the only change after cyclophosphamide was a decrease in total content of OH-proline and an increase in alpha/beta ratio of acid soluble collagen after 42 days of treatment. No effect of the subcutaneous sponge implantation was observed on the collagen variables in the skin. In comparison with unstarved controls, a reduction in dry weight and in free OH-proline in granulation tissue, as well as an increase in salt soluble OH-proline in the skin were observed 28 days after a 14-day treatment with cyclophosphamide. These observations indicate a sustained effect of cyclophosphamide on collagen 28 days after cessation of treatment. In addition the thermal stability of rat tail tendons was decreased 28 days after withdrawal of cyclophosphamide to the same extent as after starvation for 42 days and after 42 days of continuous cyclophosphamide treatment. It is concluded that the cyclophosphamide-induced collagen alterations, which may be of importance in the anti-inñammatory action of cyclophosphamide, are only in part reversible, 28 days after cessation of 14 days of cyclophosphamide treatment.     

Study of the bioavailability of different formulations of 8-methoxypsoralen in the dog

The absolute bioavailability of 8-methoxypsoralen in gelatin capsules and as a solution was studied in dogs. A dose of 2 mg kg-1 was given. Both for the solution and the gelatin capsules, a large variation in bioavailability was found between the different dogs. For the gelatin capsules in 1 dog out of 4 an absolute bioavailability of more than 100 per cent was found; for the solution a bioavailability of more than 100 per cent was found in all 4 dogs. Resorption was more rapid and bioavailability higher for the solution than for the gelatin capsules. Relative bioavailability of an emulsion and of a solution of 8-methoxypsoralen was studied in 2 dogs. A faster resorption and a higher bioavailability were found for the solution.     

Assessment of Value and Applications of In Vitro Testing of Topical Dermatological Drug Products

The FDA recently issued a guidance covering practices of scaleup and post approval changes with semisolids (SUPAC-SS). This guidance outlines the steps that must be taken by a company to maintain certification of its semisolid dermatological products after quantitative changes have been made in their compositions and/or after changes have been made in the sourcing of their key ingredients, in their processing, in their batch sizes, and/or after their site of manufacture has been relocated. A key element within the guidance is a release test to be used to determine if the diffusional release of a drug found in a formulation is the same after changes have been made to the formulation as it was prior to implementing the changes. The AAPS-FDA sponsored workshop was set up to explore this qualifying test. The stated aims of the workshop were: a) to illustrate the methodology and techniques of in vitro release testing, b) to show the sensitivity of in vitro release with respect to manufacturing variables and to variations in components and composition (of specific formulations), c) to recognize in vitro release testing as a useful procedure for SUPAC documentation, d) to highlight and evaluate other applications of in vitro release testing, e) to explore the degree to which in vitro release testing and bioavailability may be related, and f) to evaluate the role of in vitro release testing of topical dosage forms as a tool to improve product quality.     

Efficacy of and adverse effects of disopyramide

Summary The efficacy of disopyramide compared to placebo for exercise induced ventricular arrhythmias was tested in a double-blind randomized controlled clinical trial with cross-over design in 14 patients with coronary heart disease. Disopyramide was given as ordinary capsules (q.i.d.) or as a slow release preparation (b.i.d.) in a total dose of 600 mg per day. The placebo preparations were identical looking capsules and tablets. Each treatment period lasted one week. Efficacy was assessed by a standardized exercise test on a bicycle ergometer and a 6-h Holter monitoring at the end of each period.Plasma levels of disopyramide, measured in conjunction with exercise test, fell within therapeutic range, with a mean value of 7.9 and 8.9 µmol/l for capsules and slow release tablets, respectively.Disopyramide gave a marked and significant reduction of ventricular ectopic beats both at rest and during and after exercise. There was also a significant decrease in the number of ectopic beats recorded on tape during treatment periods compared to during placebo periods. There were no differences between the two preparations with respect to antiarrhythmic effect.Only mild side-effects, mainly mild anticholinergic symptoms, similar for both preparations were reported. No significant cardiovascular changes (heart rate and blood pressure response) were observed.     

Effects of different rates of absorption of two benzodiazepins on subjective and objective parameters

Summary Two benzodiazepins with different rates of absorption have been compared in a double-blind cross over study in six healthy subjects using single doses of diazepam (Valium) 2, 5 and 10 mg and oxazepam (Sobril) 15, 25 and 50 mg. Further, oxazepam formulations with different rates of absorption have been compared in 8 healthy subjects. Lastly, the diurnal variation in serum levels during long-term therapy with the benzodiazepins has been followed up in a pilot study in hospital. Drug influence was assessed at intervals and showed that the quantitative and qualitative subjective effects as well as the alteration of reaction time and hand steadiness were more pronounced during the rising phase than in the constant plateau or falling phase of serum drug concentrations. Rapidity of increase in concentration appeared more important than the absolute level. Diazepam has the faster rate of absorption and had a significantly (p<0.05–0.001) greater influence at 30 min, and usually at 90 min, too, than oxazepam or the placebo. Oxazepam, even when administered as a formulation with near-maximal absorption rate, still had not high enough a rate of absorption to produce the distinctly identifiable onset of reactions characteristic of diazepam and did not give noticeable prolongation of reaction time or increased hand unsteadiness even at its maximal serum concentrations. The separate pilot study showed that relatively large diurnal variations in serum concentrations might occur during continuous treatment for more than four weeks and that a preparation with a high rate of absorption (diazepam) could still produce a subjectively apparent experience after each individual dose. It seems reasonable to assume that the risk of abuse, and equally also one of the factors increasing the risk of habituation to psycho-pharmaceutical drugs, is related to subjectively experienced effects, which, as shown above, depend to a large extent on the rate of absorption. For maintenance treatment a steady serum level adapted to the individual is probably to be preferred, while in acute treatment, for example, of attacks of anxiety, a compound with rapid absorption is required, and the therapeutic advantages must then be weighed against the greater risk of abuse.