Conference report: Inaugural Applied Pharmaceutical Analysis: India 2010 conference

The inaugural Applied Pharmaceutical Analysis-India (APA-India) conference was held between 21 and 24 February 2010 in Hyderabad, India. The theme of the 2010 APA-India meeting was "The best of bioanalytical science in India: the role of bioanalysis and absorption, distribution, metabolism and excretion in translational medicine". The conference brought together scientists from across India and the rest of the world to stimulate discussion in the areas of discovery bioanalysis, new technologies, regulated bioanalysis and biotransformation, as applied to pharmaceutical analysis in India, the USA and other parts of the world. A total of 37 podium presentations and three webinars were presented at the 2010 APA-India meeting. The analytical tool of focus was MS with an emphasis on application to the Department of Drug Metabolism and Pharmacokinetics studies in a globalized pharmaceutical industry.     

Pharmaceutical micro-particles give amorphous sucrose higher physical stability

The aim of this study was to explore how pharmaceutical micro-sized filler particles affect the amorphous stability of sucrose in sucrose/filler particle composites produced by freeze-drying. Focus was put on the filler particles' properties crystallinity, hygroscopicity, hydrophobicity, and surface area, and their influence on physical stability of the amorphous phase. The micro-sized filler particles were examined with Blaine permeametry, gas adsorption, pycnometry, gravimetric vapour sorption, X-ray diffraction, and light microscopy before composites of sucrose and micro-sized filler particles were prepared by freeze-drying. The stability of the composites was examined with X-ray diffraction, differential scanning calorimetry (DSC), and microcalorimetry. All composites were amorphous and showed higher stability compared to pure amorphous sucrose, which was evident from a delay in heat and moisture-induced crystallization. However, calcium carbonate and oxazepam micro-sized filler particles lost their ability to stabilize the amorphous sucrose when exposed to humidity. The dry glass transition temperature (T(g)) was higher for the composites, indicating the stabilization was mediated by a reduced molecular mobility of the amorphous phase.     

Pharmaceutical microcalorimetry: applications to long-term stability studies

Calorimetry has been a mainstay of stability analyses for some time in the form of differential scanning microcalorimetry (DSC). This technique exploits high (relatively) temperature studies of pure materials and of formulations to accelerate any degradation or interactions. The behaviour of the material at storage or ambient conditions is then estimated via extrapolation from the Arrhenius equation. Recent developments in isothermal microcalorimetry allow the direct determination of both kinetic and thermodynamic parameters for long, slow reactions from studies conducted at appropriate temperatures and under designated environmental control (pH, pO2, RH etc.). This review introduces the kinetic analysis of microcalorimetric data and, through selected examples, shows applications of the method.Copyright     

A six-sigma approach to stability testing

The following defines stability testing in the diagnostic and pharmaceutical industries as a process which, depending on the manufacturer's current approach, may contain many opportunities for improvement. Statistical thinking and six sigma concepts will enhance stability testing process capability and lead to higher confidence in the data. Tools for set up and the rationale behind them are provided to assist in establishing appropriate criteria and volume of testing.     

Pharmaceutical Common Achievement Test: computer-based testing (CBT)

A six-year course of pharmaceutical education including long-term on-site practical training (pharmacy clerkship) started in the 2006 academic year in Japan. To develop good pharmacists in response to social needs, all university education programs are conducted in accordance with the Model Core Curriculum for Pharmaceutical Education in Japan and the Model Core Curriculum for Pharmacy Practical Experience. In addition to the two core curricula, each university also implements the Pharmaceutical Common Achievement Test, which is a combination of computer-based testing (CBT) and objective structured clinical examination (OSCE). The CBT is primarily used to evaluate the student's knowledge, with the student answering 310 questions chosen randomly from a pool on the computer, essentially based on the contents of the model core curriculum. On the other hand, the OSCE is used to evaluate the skills and attitudes of the student. Only students who pass the Common Achievement Test can move on to a pharmacy clerkship in a clinical setting. We review the history and present status of CBT preparation and outline the CBT. Upon examining the present situation of the CBT, it is required for the pharmaceutical scientists concerned to prepare high-quality problems based on the model core curriculum education system.     

复方奥硝唑栓的稳定性试验

目的:考察复方奥硝唑栓剂在高湿度、高温、光照条件下的稳定性.方法:按中国药典的规定进行影响因素试验,考察其性状、外观、含量、溶出度以及有关物质的变化.结果:本品在高湿(25℃、RH 92.5%、75%)、高温(35℃)务件下其性状、外观、含量、溶出率以及有关物质均符合规定;在光照(4 500±500)Lx条件下,其含量、溶出度及有关物质符合规定,但其颜色由浅黄色变为棕色.结论:本品应在凉暗处保存.     

Formulation and stability testing of photolabile drugs

Exposure of a drug to irradiation can influence the stability of the formulation, leading to changes in the physicochemical properties of the product. The influence of excipients of frequently used stabilizers is often difficult to predict and, therefore, stability testing of the final preparation is important. The selection of a protective packaging must be based on knowledge about the wavelength causing the instability. Details on drug photoreactivity will also be helpful in order to minimize side-effects and/or optimize drug targeting by developing photoresponsive drug delivery systems. This review focuses on practical problems related to formulation and stability testing of photolabile drugs.     

药品稳定性实验研究进展

阐述药品稳定性实验的研究进展。采用插入法和矩阵法设计稳定性实验可减少实验样本数，通过建立方程可预测稳定性实验中药品的含水量。稳定性实验不仅可以为获得批准文号后的各种变更提供依据，同时可减少相关变更的时间和成本。     

Failure of stability prediction for minodronic acid injectable by accelerated stability testing

A liquid formulation containing 0.5 mg/ml minodronic acid, 40 mM, pH 4.5, citrate, and sodium chloride added to adjust the osmolarity of the final formulation was stored in flint glass ampoules at 25, 40, 50, and 60 degrees C. At specified times, the drug potency and pH, and the tendency to generate particulate matter, were measured. Test samples stored at 40 degrees C for 6 months or at 50 and 60 degrees C for 3 months were stable with no potency loss and no particulate increase. However, despite the satisfactory stability at high temperatures, the amount of particulate matter increased when the formulation was stored at 25 degrees C. Scanning electron microscopy-energy dispersive X-ray analysis of the particulate matter revealed that it contains aluminum and phosphorus, the latter thought to be derived from minodronic acid. In contrast, the number of the particulate matter did not increase, when the formulation was stored in either plastic containers or in SiO(2)-treated glass ampoules(.) The spike of minodronic acid solution with aluminum ions led to the particulate generation. These results demonstrate that the particulate matter is a complex of minodronic acid molecules and aluminum ions, which apparently leached from the glass of regular ampoules. Since the particulate generation could not be observed at higher temperatures, it was suggested that the complex formation was exothermic and accelerated testing did not predict the stability in terms of particulate generation.