维生素B_(12)注射液稳定性的研究

作者用恒温加速试验法研究了维生素B_(12)注射液的稳定性。结果表明:该注射液的稳定性在pH值4.80左右较好,加络合剂可增加其稳定性,有效期为5年。     

Effects of storage time and temperature on the properties of two self-etching systems

OBJECTIVES: To evaluate the micro-shear bond strength to enamel and dentin, pH and hardness of two self-etching adhesives over a period of 60 weeks storage at different temperatures. MATERIALS AND METHODS: Two self-etching systems, an all-in-one adhesive, Clearfil Tri-S Bond (TS) and a two-step adhesive, Clearfil SE Bond (SE) were used in this study (both by Kuraray Medical, Osaka, Japan). Their micro-shear bond strengths to enamel and dentin were measured. The materials were then stored at 4, 23 or 37 degrees C. Their bond strengths were measured again after 1, 4, 16 and 60 weeks and compared to the base line. The nano-indentation hardness of the polymerized bonding, pH of SE primer and TS were also measured at the baseline and after 60 weeks of storage at three different temperatures. Bond-strength and hardness data were analyzed using ANOVA and post hoc tests at the significance level of 0.05. RESULTS: Two-way ANOVA analysis showed that both storage conditions and material type had significant effects on bond strength to enamel or dentin but the interactions of these factors were not significant for any of the substrates. One-way ANOVA post hoc tests revealed that the bond strength of adhesives stored at 37 degrees C significantly decreased during the storage period; with the earliest significant decreases observed at 4 weeks for TS and at 16 weeks for SE. After 60 weeks of storage, the hardness obtained for SE bonding resin was not significantly different with that at the baseline for 4, 23 and 37 degrees C groups, but there was a significant decrease observed in hardness for TS stored at 37 degrees C, compared to that at the baseline. The pH of both self-etching materials decreased when they were stored at 37 degrees C. CONCLUSION: Storage time and temperature significantly affected the bond strength of both materials through the time dependent hydrolysis and other changes that are likely to occur in the water-containing self-etching agents at high temperatures.     

Test for batch-to-batch variation in stability analysis

We propose several statistical tests for batch-to-batch variation in the stability analysis of a drug product and present applications with data from new drug application stability and marketing stability analyses.     

Aamar-e-Advia (shelf-lives) of drugs in Unani system of medicine: A conceptual review

In an era of globalization and increased global demand for herbal medicines, it is essential to ensure the quality and consistency of drugs. Changes in the quality of an herbal product over time should be detectable. The assessments of chemical quality and therapeutic efficacy of herbal drugs are necessary to establish their shelf-lives. Thus, stability testing is needed to establish standards for herbal products. Unani medicine has its own conceptual framework for studying health and disease. The mode of treatment includes Ilaj bit Tadbeer (regimental therapy), Ilaj bil Ghiza (dietotherapy), Ilaj bil Dawa (pharmacotherapy) and Ilaj bil Yad/Jarahat (surgery) as a final option. Ilaj bil Dawa is the most used mode of treatment. The drugs include either crude drugs prepared from plant, animal and mineral sources, called Mufrad (single) drugs or various formulations prepared from these crude drugs, called Murakkab (compound) drugs. To date, stability studies have been carried out on compound drugs, whereas only a few single drugs had had their stability tested. These studies are needed to understand how the quality of an herbal drug varies over the time when it is prepared and consumed. This may also help to standardize procedures for manufacturing compound formulations ab initio. The present study reviews the concept of Aamar-e-Advia (shelf-lives) described in the literature of the Unani system of medicine. Further, various factors that are considered important to assess the shelf-life of Unani drugs are discussed in the context of contemporary protocols for shelf-life assessment.     

10%苯巴比妥钠注射液贮存期预测

The shelf-life of 10% sodium phenobarbital injection(containing propylene glycol 60%) has been predicted by accelerated stability test with the classical isothermal method (at 100, 90, 80 and 70℃). The data was treated with regressive calculation, and the shelf-life calculated with three different methods (regressive calculation, average activation energy calculation and graphical plotting).The values obtained from these three methods were approximately equal, and also coincided with the value obtained from samples reserved for observation at room temperature. The shelf-life was 1.05 years at 25℃, and 2.03 years at 20℃.     

药物在室内自然光照射下的贮存期预测方法研究

以己酸孕酮注射液为例,研究了药物在自然光和不同灯光照射下的含量变化规律,预测了药物在室内自然光照射下的贮存期。找出了不同光源对药物稳定性影响的等效数量关系,使在今后的研究中可以用灯光为光源预测药物在室内自然光照射下的贮存期。己酸孕酮注射液在光照试验中含量变化服从零级反应规律:C=C₀-K(Et),在室内自然光照射下的贮存期约为1.9年。     

APS（黄芪多糖）脂质体的制备、稳定性和免疫促进作用

用均匀设计法设置6因素10水平考察了APS脂质体制备条件，通过计算机处理结果选出适合于大规模工业化生产的最佳制备条件。APS脂质体20℃贮存期为1.46年。90％以上的微粒直径小于1μm,40℃放置三个月，粒径仍未改变，通过检测APS脂质体对小鼠中性粒细胞蚕噬作用，血清溶血素水平和迟发型超敏反应的影响，发现APS脂质体有较强的免疫促进作用。本项研究建立了APS脂质体生产和临床应用的基础。     

A Bayesian Approach to Setting the Release Limits for Critical Quality Attributes

To ensure the safety, efficacy, and quality, regulatory authorities require that multiple critical quality attributes of a drug must conform to certain specification limits. Manufacturers must establish a set of release limits for drug substance or final drug product batches, so that the released drug product batches remain within the specification limits during the whole shelf-life. Various statistical methods have been proposed to determine the release limits such that the probability of out-of-specification at the end of shelf-life will be controlled under a desirable level. Stringent release limits result in tight quality control of the drug quality, thus protecting consumer's risk. On the other hand, overly tight release limits may cause unnecessary rejection of a good batch of drug substance or drug product, resulting increased manufacturer's risk. Therefore, the release limits should be constructed to control both the consumer's risk of releasing a bad batch to the market and the manufacturer's risk of rejecting a good batch. Since the pharmaceutical release procedure is complex and usually consists of many quality-control steps, a holistic strategy for risk management shall be established. In this article, we propose a Bayesian approach for determining the release limits for critical quality attributes to keep the balance of both types of risks in the situation of multiple process steps and storage conditions. The proposed method is easy to implement and can be used to control the risks of intermediate steps as well as the holistic risk of a multi-step drug release process.     

Ultrasonication and encapsulation of Butcher broom (Ruscus Hyrcanus L.) extract and its bioactive effects on qualitative properties,oxidative stability and shelf life of cake

Three solvents of pure-water (PW), 50:50 ethanol-water (EW) and pure-ethanol (PE) were used to obtain phytochemicals of Butcher's broom (Ruscus Hyrcanus L) leaves (BBL) separately with 10% concentrations (w/w) at 20 °C for 48 h. Since the extract yield of EW was higher than other solvents, therefore 100, 300, 500 and 700 mg/L of BBL were macerated separately at similar conditions and ultrasonicated in 37 kHz at 35 °C for 35 min. The yield of ultrasound assisted extraction (UAE) of EW had significantly (P ≤ 0.05) higher DPPH, ferric reducing antioxidant power (FRAP), phenolic, anthocyanin and flavonoids than EW extract before sonication at each BBL concentration. Then the yield of UAE at 700 mg/L was nano-capsulated (NC) with the mixture of (50:50) maltodextrin/gum Arabic (MD/GA). The NC efficiency and the coated-particle sizes were 80.48% and 95.17 nm, respectively. Furthermore, the scanning electron microscopy (SEM) and test of Fourier-transform infrared spectroscopy (FTIR) confirmed successful encapsulation and interactions between the final extract yield and coating layer of MD/GA. The UAE extracts of 700 mg/L with and without encapsulation were separately added into the prepared cake dough at 0.7%. Analysis of baked cakes during 45-day storage at 20 °C showed that thiobarbituric acid, peroxide values, yeast, mold and total viable count of NC-samples were significantly (P ≤ 0.05) lower than non-capsulated UAE-sample and control (cake without any extract). The MD/GA layer of NC-sample could protect the BBL phytochemicals and extend the shelf life of cake significantly longer (without negative quality indictors) due to its stable coating at 150 °C baking temperature.     

Effect of pH, ionic strength and oxygen burden on the chemical stability of EPC/cholesterol liposomes under accelerated conditions: Part 1: Lipid hydrolysis

The accelerated stability of purified egg phosphatidylcholine (EPC)/cholesterol liposomes was studied under various formulation conditions using a 2³ factorial experimental design. The three factors included in the study were pH, ionic strength of the buffer and the headspace oxygen content in the container. The results showed that lipid hydrolysis followed pseudo first-order kinetics. Data analysis using factorial design revealed that pH of the buffer was the predominant factor influencing the rate of lipid hydrolysis. Neither the ionic strength of the buffer, nor the presence of oxygen in the headspace of the container significantly affected the EPC hydrolysis. The hydrolysis rate of EPC at pH 4.0 buffer was at least 1.75 times greater than that at pH 4.8. A prediction based on the Arrhenius equation suggests that the EPC/cholesterol liposomes should be formulated in a buffer with pH equal to or greater than 4.2 in order to have a shelf-life longer than 1 year at 5°C.