Subcritical water extraction and determination of nifedipine in pharmaceutical formulations

A rapid and simple continuous method for the extraction of nifedipine from tablets was developed by using pressurized hot water at 150 degrees C. This is the first time that subcritical water was applied to the extraction of low-polarity compounds in pharmaceutical analysis. The method is based on the increment in solubility of nifedipine in subcritical water. Extraction temperature and static and dynamic extraction time were optimized in order to reach quantitative extraction of the drug from the tablets. After extraction, the drug was determined by spectrophotometry by measuring absorbance at 338 nm. Accuracy and precision of the method were determined by analysis of 10 synthetic samples of pharmaceutical formulations prepared with common tablet excipients. Recovery was found to be 99.2% with a relative standard deviation of 1.9%, which indicates that the excipients of the formulation do not interfere in the determination. The method was applied to the determination of the drug content uniformity in tablets.     

Hermitian Curvature and Plurisubharmonicity of Energy on Teichmüller Space

Let M be a closed Riemann surface, N a Riemannian manifold of Hermitian non-positive curvature, f : M → N a continuous map, and E the function on the Teichmüller space of M that assigns to a complex structure on M the energy of the harmonic map homotopic to f. We show that E is a plurisubharmonic function on the Teichmüller space of M. If N has strictly negative Hermitian curvature, we characterize the directions in which the complex Hessian of E vanishes.     

Predicting the reaction mechanism of nucleophilic substitutions at carbonyl and thiocarbonyl centres of esters and thioesters

In nucleophilic substitution reactions at carbonyl centres, there are two possible channels. The first one occurs when the attack of nucleophilic agents takes place simultaneously with the departure of the nucleofuge. This process is named as concerted. The second possibility is the formation of a reaction intermediate, typically a tetrahedral intermediate from which the nucleofuge departs after passing through a second transition state. This second mechanism is defined as stepwise. Whether a concerted or stepwise mechanism is to be expected for a given reaction depends on several factors. Among these determinants are the nucleophilicity of the attacking group, the leaving group ability of the nucleofuge, and the solvent, which affects both the stability of the intermediate or the transition states involved. The role of the electrophilic centre can however become an important factor that can determine the reaction mechanism. In this work we show that the group nucleophilic Fukui function model may be used to rationalize and to predict the reaction mechanism of the title compounds towards alicyclic amines. In general, when the electrophilic carbon centre is attached to the soft sulfur atom, the reaction mechanism is predicted to follow a stepwise route. When the electrophilic carbon atom is attached to a harder oxygen centre, the reaction mechanism is determined by chemical substitution at the nucleofuge moiety. Experimental verification for a set of four substrates is presented. Copyright © 2012 John Wiley & Sons, Ltd.     

Nonparametric significance tests for imperfect repair

Given the failure history for $K\ge 2$ independent and identical repairable systems, a nonparametric procedure is presented to test the null hypothesis of minimal repair (MR) against the alternative of imperfect repair. The main idea is that, under non-harmful (harmful) repair, systems that failed later (earlier) are more reliable than those that have failed (later). This fact allows one, at any moment in time, to rank the systems from more to less reliable and, hence, to define a vector that counts how many times the system ranked $r$ failed. When all the systems are time-truncated at the same time $T$, it is shown that, under the null hypothesis of MR, the vector of counts follows a multinomial distribution with class probabilities $p_r=K^{-1}$ for $r=1,\dots ,K$. The test proceeds by computing a chi-bar squared test statistic similar to the one used to test one-sided alternatives in the multinomial setup, which allows us to compute $p$-values using either asymptotic theory or a straightforward Monte Carlo simulation using the null multinomial distribution. Extension to the case of different truncation times is also discussed. The procedure is applied to two real datasets regarding equipment used in the mining industry.