Erratum to: Multiple Response Optimization of a HPLC Method for the Determination of Enantiomeric Purity of S-Ofloxacin

The aim of the study was to develop a new HPLC method for direct chiral separation of Ofloxacin enantiomers using polar non-aqueous mobile phase by application of response surface methodology. Rotatable central composite design (CCD) with eight factorial points, six axial points and six replications in central point was used to evaluate the influence of three independent variables (concentration of methanol, diethylamine and flow rate) on the output responses (capacity factor of first peak, tailing factors of both the enantiomers, resolution between the Ofloxacin enantiomers, retention time of the last peak and chromatographic optimization function). Further, CCD data were combined with multiple response optimization in order to obtain a set of optimal experimental conditions (% methanol/hexane/acetonitrile-43.33/10/46.62 (v/v), % acetic acid/diethylamine-0.4/0.2 and flow rate as 1.4 mL min⁻¹) leading to the most desirable compromise between resolution and analysis time. The method demonstrated good correlation between observed and predicted responses. The developed method was validated according to ICH guidelines and applied for quantitative analysis of two commercially available tablets Zenoflox (Ofloxacin) and Glevo (Levofloxacin). Good agreement was found between the assay results and the label claim of the marketed formulations by showing good %recovery and %CV. The study resulted in a better chromatographic system for the determination of Ofloxacin enantiomers.

     

Slope stability analysis using fracture mechanics approach

The analysis of slope failure is complicated due to its mechanism as well as the geological history of the slope. In classical slope stability analysis, the slope failure is assessed using the basic continuum mechanics or the limit equilibrium approach. This analysis, however, must be slightly modified when tension cracks exist at the upper edge of the slope. From post-mortem analyses of slope failures in the past, it was found that tension cracks had some considerable importance affecting the failure mechanism of the slope.Some attempts had also been directed in the past towards simple vertical cut slopes with tension cracks. Terzaghi [40]. Using an elasto-plastic model and a few analytical assumptions, Terzaghi [40] obtained an expression for a critical height of a vertical cut slope. However, since the stress distribution is changing during crack propagation, the failure mechanism cannot in principle conjecture from a static (undisturbed) stress field alone. In this report, a unified numerical approach combining Finite Element Method (FEM), fracture mechanics and remeshing technique is used to model the failure analysis of vertical cut slopes with tension cracks. Using this approach, the crack can be extended incrementally under a certain energy based failure criterion (Strain Energy Density criterion - SED) while taking into account the existing stress singularity field in the vicinity of the crack-tip.The use of fracture mechanics in soils, however, poses some difficulties in obtaining its relevant parameters due to the granular structure of soil. Because of its granular structure, the shear strength of soil depends on cohesion and the applied confining pressure making the determination of fracture parameters in soil difficult. These relevant parameters are not yet available in literature and hence, certain assumptions and interpolations had to be made in obtaining these parameters. Future research direction in this area is badly needed. Using a certain set of soil properties and crack geometry, a series of curves relating parameters S (Strain Energy Density Factor) and a non-dimensional variable N ( = H/C - slope height vs. crack distance from edge ratio) for vertical cut slopes can be constructed through numerous parametric studies. These curves can serve as a quick guide to obtain the critical height for a given vertical cut slope geometry with tension cracks.     

Multiple Response Optimization of a HPLC Method for the Determination of Enantiomeric Purity of S-Ofloxacin

The aim of the study was to develop a new HPLC method for direct chiral separation of Ofloxacin enantiomers using polar non-aqueous mobile phase by application of response surface methodology. Rotatable central composite design (CCD) with eight factorial points, six axial points and six replications in central point was used to evaluate the influence of three independent variables (concentration of methanol, diethylamine and flow rate) on the output responses (capacity factor of first peak, tailing factors of both the enantiomers, resolution between the Ofloxacin enantiomers, retention time of the last peak and chromatographic optimization function). Further, CCD data were combined with multiple response optimization in order to obtain a set of optimal experimental conditions (% methanol/hexane/acetonitrile-43.33/10/46.62 (v/v), % acetic acid/diethylamine-0.4/0.2 and flow rate as 1.4 mL min^?1) leading to the most desirable compromise between resolution and analysis time. The method demonstrated good correlation between observed and predicted responses. The developed method was validated according to ICH guidelines and applied for quantitative analysis of two commercially available tablets Zenoflox (Ofloxacin) and Glevo (Levofloxacin). Good agreement was found between the assay results and the label claim of the marketed formulations by showing good %recovery and %CV. The study resulted in a better chromatographic system for the determination of Ofloxacin enantiomers.     

An improved HPLC method with the aid of a chemometric protocol: simultaneous analysis of amlodipine and atorvastatin in pharmaceutical formulations

Statistical experimental design and Derringer's desirability function were applied to develop an improved RP-HPLC method for the simultaneous analysis of amlodipine and atorvastatin in pharmaceutical formulations. Four independent factors were considered: acetonitrile content in the mobile phase; buffer pH; buffer concentration; and flow rate. The preliminary screening step was carried out, according to a 2(4-1) fractional factorial design, to identify the significant factors affecting the analysis time response. Then central composite design was applied for a response surface study, in order to examine in depth the effects of the most important factors. Subsequently, Derringer's desirability function was employed to simultaneously optimize the six responses: retention factor of first peak; two resolutions; and three retention times, each having a different target. This procedure allowed deduction of two separate optimum conditions, intended for the analysis of quality control and plasma samples, within the experimental domain. The predicted optimum for the quality control samples was: methanol-acetonitrile-15 mM K(2)HPO(4) buffer (pH 5.33) (10:42.08:47.92, v/v/v) as the mobile phase and 1.12 mL/min as the flow rate. The method using this optimized condition showed higher sensitivity and shorter analysis time than the previously published reports. The optimized assay condition was validated according to International Conference on Harmonization guidelines.     

Ultrasound-promoted regioselective and stereoselective synthesis of novel spiroindanedionepyrrolizidines by multicomponent 1,3-dipolar cycloaddition of azomethine ylides

A series of novel spiroindanedionepyrrolizidines have been synthesized by multicomponent 1,3-dipolar cycloaddition of a variety of (E)-3-aryl-1-(thiophen-2-yl)prop-2-en-1-ones with unstabilized azomethine ylides generated from ninhydrin and l-proline. The reactions were highly regioselective and stereoselective and were conducted with both conventional heating and ultrasonic irradiation conditions. In general, milder conditions, and moderate improvement in rates, reaction times, and yields were observed when the reactions were performed under ultrasonic conditions. The regioselective and stereoselective nature of the products was established by use of single-crystal X-ray structure and spectroscopic techniques.     

Direct Chiral HPLC Method for the Simultaneous Determination of Warfarin Enantiomers and Its Impurities in Raw Material and Pharmaceutical Formulation: Application of Chemometric Protocol

Warfarin is a well-known anticoagulant agent that occurs in two enantiomers, (R)-(+)-warfarin and (S)-(?)-warfarin, in which 4-hydroxycoumarin and benzalacetone are commonly found as impurities. Due to the lack of analytical reports for the simultaneous estimation on warfarin and its impurities in bulk drug and pharmaceuticals, we aim at the simultaneous estimation and optimization of the chromatographic separation of warfarin and its related substances employing experimental design. Central composite design was employed to evaluate the influence of two independent variables (concentration of organic modifier and flow rate) on the output responses: capacity factor (k ₁), resolution of the peak (Rs _3,4), and retention time of the last peak (tR ₅), as well as to model these responses. Further, the central composite design results were combined in a multicriteria decision-making approach in order to obtain a set of optimal experimental conditions leading to the most desirable compromise between resolution and analysis time.