A Concise Review Based on Analytical Method Development and Validation of Apremilast in Bulk and Marketed Dosage Form

Apremilast is used for treatment of psoriasis and psoriatic arthritis. It may also be beneficial for other inflammatory diseases relevant to the immune system. The drug functions as a selective enzyme phosphodiesterase 4 (PDE4) inhibitor and avoids the spontaneous development of TNF-alpha from human synovial rheumatoid cells. The present review assesses the different approaches for evaluation of apremilast in bulk material as well as different formulations. A concise review consists of compile and discuss about over 30 methods for analysing apremilast in the biological matrices, the samples of bulk and in different dosage formulations including HPLC, HPTLC, UPLC, LC-MS and UV-spectrophotometry. A concise review represents the compilation and discussion of about more than 30 analytical methods which includes HPLC, HPTLC, UPLC, LC-MS and UV-Spectrophotometry methods implemented for investigation of apremilast in biological matrices, bulk samples and in different dosage formulations. This detailed review will be of great help to the researcher who is working on apremilast. Keywords: Apremilast; Analytical Profile; HPLC; HPTLC; Bioanalytical; Stability indicatin

Dual mechanism model for fluid particle breakup in the entire turbulent spectrum

This work provides an in-depth understanding of different breakup mechanisms for fluid particles in turbulent flows. All the disruptive and cohesive stresses are considered for the entire turbulent energy spectrum and their contributions to the breakup are evaluated. A new modeling framework is presented that bridges across turbulent subranges. The model entails different mechanisms for breakup by abandoning the classical limitation of inertial models. The predictions are validated with experiments encompassing both breakup regimes for droplets stabilized by internal viscosity and interfacial tension down to the micrometer length scale, which covers both the inertial and dissipation subranges. The model performance ensures the reliability of the framework, which involves different mechanisms. It retains the breakup rate for inertial models, improves the predictions for the transition region from inertia to dissipation, and bridges seamlessly to Kolmogorov-sized droplets

Comparison of the Dielectric Response Obtained from Fluorescence Upconversion Measurements and Molecular Dynamics Simulations for Coumarin 153−Apomyoglobin Complexes and Structural Analysis of the Complexes by NMR and Fluorescence Methods

We present a comparison of the dielectric response obtained from fluorescence upconversion experiments and from molecular dynamics simulations of the complexes of coumarin 153 with five apomyoglobins (apoMbs): wild-type horse heart (HH-WT) and those of wild-type sperm whale (SW-WT); its two triple mutants, L29F/H64Q/V68F and H64L/V68F/P88A; and its double mutant, L29F/V68L. Comparisons between experimental and simulated solvation relaxation functions, C(t)s, for the wild-type proteins range from very good to excellent. For the three mutants we investigated, however, agreement between experiment and simulation was considerably inferior. Thus, an NMR study of the complex of the HH-WT complex apoMb, and fluorescence energy transfer and anisotropy studies of the five complexes, were performed to investigate the structures upon which the simulations were based. The NMR measurements confirm our earlier conclusions that the C153 lies in the heme pocket of the HH-WT apoMb. For the wild-type complexes, fluorescence energy transfer measurements provide two rise times, suggesting a definite spatial relationship between the two Trp donors and the C153 acceptor. These results confirm the structural integrity of the wild-type complexes and validate the initial structures used for the molecular dynamics simulations. On the other hand, the three mutants provided single exponential rise times for energy transfer, suggesting that the position of the C153 used in the simulations may have been in error or that the C153 is mobile on the time scale of the energy transfer experiment. Fluorescence anisotropy studies also suggest that the double mutant was not structurally intact. Furthermore, examination of these systems demonstrates the sensitivity of C153 to its environment and permits the observation of differences in the heme pockets. These results point to the importance of structural characterization of modified proteins used in studies of the dielectric response and suggest strategies for performing molecular dynamics simulations of modified proteins

Bistability versus Bimodal Distributions in Gene Regulatory Processes from Population Balance

In recent times, stochastic treatments of gene regulatory processes have appeared in the literature in which a cell exposed to a signaling molecule in its environment triggers the synthesis of a specific protein through a network of intracellular reactions. The stochastic nature of this process leads to a distribution of protein levels in a population of cells as determined by a Fokker-Planck equation. Often instability occurs as a consequence of two (stable) steady state protein levels, one at the low end representing the “off” state, and the other at the high end representing the “on” state for a given concentration of the signaling molecule within a suitable range. A consequence of such bistability has been the appearance of bimodal distributions indicating two different populations, one in the “off” state and the other in the “on” state. The bimodal distribution can come about from stochastic analysis of a single cell. However, the concerted action of the population altering the extracellular concentration in the environment of individual cells and hence their behavior can only be accomplished by an appropriate population balance model which accounts for the reciprocal effects of interaction between the population and its environment. In this study, we show how to formulate a population balance model in which stochastic gene expression in individual cells is incorporated. Interestingly, the simulation of the model shows that bistability is neither sufficient nor necessary for bimodal distributions in a population. The original notion of linking bistability with bimodal distribution from single cell stochastic model is therefore only a special consequence of a population balance model

Crossover between Rayleigh-Taylor Instability and turbulent cascading atomization mechanism in the bag-breakup regime

The question whether liquid atomization (or pulverization) resorts to instability dynamics (through refinements of Rayleigh-Plateau, Rayleigh-Taylor or Kelvin-Helmholtz mechanism) or to turbulent cascades similar to Richardson and Kolmogorov first ideas seems to be still open. In this paper, we report experimental evidences that both mechanisms are needed to explain the spray drop PDF obtained from an industrial nozzle. Instability of Rayleigh-Taylor kind governs the size of the largest droplets while the smallest ones obey a PDF given by a turbulent cascading mechanism resulting in a log-L\'evy stable law of stability parameter close to 1.68. This value, very close to the inverse of the Flory exponent, can be related to a recent model for intermittency modeling stemming from self-avoiding random vortex stretching.Comment: new alpha version (precedent was a draft

Stover Quality Traits for Improvement of Dual-Purpose Sorghum

Twenty four sorghum stovers were investigated with sheep for organic matter digestibility (OMD) and intake (OMI), and for digestible organic matter intake (DOMI) and for relations between laboratory fodder quality traits and these in vivo measurements. Statistically highly significant and nutritionally important differences were found between the stover with OMD differing by 15 percentage units and OMI and DOMI varying 1.6 and 2 times, respectively. For each of the in vivo measurements, chemical (NDF, ADF, ADL) and in vitro (in vitro digestibility, metabolisable energy content) traits were identified which accounted for at least 50% of the variation in the respective traits. Using multiple regression procedures and stringent cross-validation (“blind-predictions”) procedures OMD, OMI and DOMI could be predicted with R2 for comparing observed and predicted values of 0.36, 0.65 and 0.75, respectively. The reported research showed selection for dual purpose sorghum cultivars is promising, and identified and validated simple laboratory traits that can be used for such phenotypin