Quantification of erythromycin in pharmaceutical formulation by transmission Fourier transform infrared spectroscopy

A simple, cost-effective and environmental friendly analytical method was developed for the quantification of erythromycin in tablet formulation using transmission Fourier Transform Infrared (FT-IR) spectroscopy for routine quality control analysis. There is no need of sample preparation except pellet formation for FT-IR analysis. Use of solvent was totally avoided in this method. Calibration was carried out by using simple Beer’s law in the FT-IR region between 1743 and 1697 cm⁻¹. The excellent coefficient of determination (R² = 0.998) was achieved with 0.0247 and 1.14 root mean square error of prediction (RMSEP) and root mean square error of cross validation (RMSECV), respectively. The results of the study revealed that the transmission FT-IR spectroscopy could be effectively used for rapid determination of active ingredients like erythromycin in pharmaceutical formulations to control the quality of finished products.     

Solubility and Stability of Some Pharmaceuticals in Natural Deep Eutectic Solvents-Based Formulations

Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0–30% (w/w) was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid–propyleneglycol could dissolve spironolacton and trimethoprim at a concentration up to 50 and 100 mg/mL, respectively. The results showed that NADES are promising solvents for formulation of poorly water-soluble medicines for the development of parenteral and tube feeding administration of non-water-soluble medicines. The chemical stability and bioavailability of these drug in NADES needs further studies.     

On the Rational Drug Design for Hypertension through NMR Spectroscopy

Antagonists of the AT1receptor (AT1R) are beneficial molecules that can prevent the peptide hormone angiotensin II from binding and activating the specific receptor causing hypertension in pathological states. This review article summarizes the multifaced applications of solid and liquid state high resolution nuclear magnetic resonance (NMR) spectroscopy in antihypertensive commercial drugs that act as AT1R antagonists. The 3D architecture of these compounds is explored through 2D NOESY spectroscopy and their interactions with micelles and lipid bilayers are described using solid state ¹³CP/MAS, ³¹P and ²H static solid state NMR spectroscopy. Due to their hydrophobic character, AT1R antagonists do not exert their optimum profile on the AT1R. Therefore, various vehicles are explored so as to effectively deliver these molecules to the site of action and to enhance their pharmaceutical efficacy. Cyclodextrins and polymers comprise successful examples of effective drug delivery vehicles, widely used for the delivery of hydrophobic drugs to the active site of the receptor. High resolution NMR spectroscopy provides valuable information on the physical-chemical forces that govern these drug:vehicle interactions, knowledge required to get a deeper understanding on the stability of the formed complexes and therefore the appropriateness and usefulness of the drug delivery system. In addition, it provides valuable information on the rational design towards the synthesis of more stable and efficient drug formulations.     

Phytochemical and Biological Evaluation of a Newly Designed Nutraceutical Self-Nanoemulsifying Self-Nanosuspension for Protection and Treatment of Cisplatin Induced Testicular Toxicity in Male Rats

The incorporation of cisplatin (CP) as a cytotoxic antineoplastic agent in most chemotherapeutic protocols is a challenge due to its toxic effect on testicular tissues. Natural compounds present a promising trend in research, so a new nutraceutical formulation (NCF) was designed to diminish CP spermatotoxicity. A combination of three nutraceutical materials, 250 mg Spirulina platensis powder (SP), 25 mg Tribulus terrestris L. extract (TT), and 100 mg fish oil (FO) were formulated in self-nanoemulsifying self-nanosuspension (SNESNS). SP was loaded into the optimized self-nanoemulsifying system (30% FO, 50% span 80/cremophor EL and 20% isopropanol) and mixed with TT aqueous solution to form SNESNS. For the SP, phytochemical profiling revealed the presence of valuable amounts of fatty acids (FAs), amino acids, flavonoids, polyphenols, vitamins, and minerals. Transmission electron microscopy (TEM) and particle size analysis confirmed the formation of nanoemulsion-based nanosuspension upon dilution. Method validation of the phytochemical constituents in NCF has been developed. Furthermore, NCF was biologically evaluated on male Wistar rats and revealed the improvement of spermatozoa, histopathological features, and biochemical markers over the CP and each ingredient group. Our findings suggest the potential of NCF with SNESNS as a delivery system against CP-induced testicular toxicity in male rats.     

Simultaneous densitometric determination of anthelmintic drug albendazole and its metabolite albendazole sulfoxide by HPTLC in human plasma and pharmaceutical formulations

A new, simple, accurate and precise high‐performance thin‐layer chromatographic method has been developed and validated for simultaneous determination of an anthelmintic drug, albendazole, and its active metabolite albendazole, sulfoxide. Planar chromatographic separation was performed on aluminum‐backed layer of silica gel 60G F₂₅₄ using a mixture of toluene–acetonitrile–glacial acetic acid (7.0:2.9:0.1, v /v/v) as the mobile phase. For quantitation, the separated spots were scanned densitometrically at 225 nm. The retention factors (R _f) obtained under the established conditions were 0.76 ± 0.01 and 0.50 ± 0.01 and the regression plots were linear (r ² ≥ 0.9997) in the concentration ranges 50–350 and 100–700 ng/band for albendazole and albendazole sulfoxide, respectively. The method was validated for linearity, specificity, accuracy (recovery) and precision, repeatability, stability and robustness. The limit of detection and limit of quantitation found were 9.84 and 29.81 ng/band for albendazole and 21.60 and 65.45 ng/band for albendazole sulfoxide, respectively. For plasma samples, solid‐phase extraction of analytes yielded mean extraction recoveries of 87.59 and 87.13% for albendazole and albendazole sulfoxide, respectively. The method was successfully applied for the analysis of albendazole in pharmaceutical formulations with accuracy ≥99.32%.     

An extension of implicit Monte Carlo diffusion: Multigroup and the difference formulation

Implicit Monte Carlo (IMC) and Implicit Monte Carlo Diffusion (IMD) are approaches to the numerical solution of the equations of radiative transfer. IMD was previously derived and numerically tested on grey, or frequency-integrated problems [1]. In this research, we extend Implicit Monte Carlo Diffusion (IMD) to account for frequency dependence, and we implement the difference formulation [2] as a source manipulation variance reduction technique. We derive the relevant probability distributions and present the frequency dependent IMD algorithm, with and without the difference formulation. The IMD code with and without the difference formulation was tested using both grey and frequency dependent benchmark problems. The Su and Olson semi-analytic Marshak wave benchmark was used to demonstrate the validity of the code for grey problems [3]. The Su and Olson semi-analytic picket fence benchmark was used for the frequency dependent problems [4]. The frequency dependent IMD algorithm reproduces the results of both Su and Olson benchmark problems. Frequency group refinement studies indicate that the computational cost of refining the group structure is likely less than that of group refinement in deterministic solutions of the radiation diffusion methods. Our results show that applying the difference formulation to the IMD algorithm can result in an overall increase in the figure of merit for frequency dependent problems. However, the creation of negatively weighted particles from the difference formulation can cause significant numerical instabilities in regions of the problem with sharp spatial gradients in the solution. An adaptive implementation of the difference formulation may be necessary to focus its use in regions that are at or near thermal equilibrium.     

Optimal control for reinitialization in finite element level set methods

A new optimal control problem that incorporates the residual of the Eikonal equation into its objective is presented. The formulation of the state equation is based on the level set transport equation but extended by an additional source term, correcting the solution so as to minimize the objective functional. The method enforces the constraint so that the interface cannot be displaced at least in the continuous setting. The system of first‐order optimality conditions is derived, linearized, and solved numerically. The control also prevents numerical instabilities, so that no additional stabilization techniques are required. This approach offers the flexibility to include other desired design criteria into the objective functional. The methodology is evaluated numerically in three different examples and compared with other PDE‐based reinitialization techniques. Copyright © 2016 John Wiley & Sons, Ltd.     

Higher-order streamfunction-vorticity formulation of 2D steady-state Navier-Stokes equations

Based on regular boundary element method and a kind of linearity invariance under homotopy, a kind of numerical scheme of 2D steady-state Navier-Stokes equation in streamfunction-vorticity formulation is described. The flow inside a square cavity is used to illustrate this numerical scheme.     

Substructuring preconditioners for the three fields domain decomposition method

We study a class of preconditioners based on substructuring, for the discrete Steklov-Poincaré operator arising in the three fields formulation of domain decomposition in two dimensions. Under extremely general assumptions on the discretization spaces involved, an upper bound is provided on the condition number of the preconditioned system, which is shown to grow at most as ( and denoting, respectively, the diameter and the discretization mesh-size of the subdomains). Extensive numerical tests--performed on both a plain and a stabilized version of the method--confirm the optimality of such bound.

     

Equilibrium schemes for scalar conservation laws with stiff sources

We consider a simple model case of stiff source terms in hyperbolic conservation laws, namely, the case of scalar conservation laws with a zeroth order source with low regularity. It is well known that a direct treatment of the source term by finite volume schemes gives unsatisfactory results for both the reduced CFL condition and refined meshes required because of the lack of accuracy on equilibrium states. The source term should be taken into account in the upwinding and discretized at the nodes of the grid. In order to solve numerically the problem, we introduce a so-called equilibrium schemes with the properties that (i) the maximum principle holds true; (ii) discrete entropy inequalities are satisfied; (iii) steady state solutions of the problem are maintained. One of the difficulties in studying the convergence is that there are no estimates for this problem. We therefore introduce a kinetic interpretation of upwinding taking into account the source terms. Based on the kinetic formulation we give a new convergence proof that only uses property (ii) in order to ensure desired compactness framework for a family of approximate solutions and that relies on minimal assumptions. The computational efficiency of our equilibrium schemes is demonstrated by numerical tests that show that, in comparison with an usual upwind scheme, the corresponding equilibrium version is far more accurate. Furthermore, numerical computations show that equilibrium schemes enable us to treat efficiently the sources with singularities and oscillating coefficients.