Solid state nuclear magnetic resonance studies of hydroxypropylmethylcellulose acetyl succinate polymer,a useful carrier in pharmaceutical solid dispersions

Hydroxypropylmethylcellulose (HPMC) acetyl succinate (HPMC-AS) is a key polymer used for the enablement of amorphous solid dispersions (ASDs) in oral solid dosage forms. Choice of the appropriate grade within the material is often made empirically by the manufacturer of small-scale formulations, followed by extensive real time stability. A key factor in understanding and predicting the performance of an ASD is related to the presence of hydrogen (or other) bonds between the polymer and active pharmaceutical ingredient (API), which will increase stability over the parameters captured by miscibility and predicted by the Gordon–Taylor equation. Solid state nuclear magnetic resonance (NMR) is particularly well equipped to probe spatial proximities, for example, between polymer and API; however, in the case of HPMC-AS, these interactions have been sometimes difficult to identity as the carbon-13 NMR spectra assignment is yet to be firmly established. Using feedstock, selectively substituted HPMC polymers, and NMR editing experiments, we propose here a comprehensive understanding of the chemical structure of HPMC-AS and a definitive spectral assignment of the ¹³C NMR spectra of this polymer. The NMR data also capture the molar ratios of the acetate and succinate moieties present in HPMC-AS of various grades without the need for post treatment required by chromatography methods commonly use in pharmacopoeia. This knowledge will allow the prediction and measurement of interactions between polymers and APIs and therefore a rational choice of polymer grade to enhance the solid state stability of ASDs.     

HPLC/PDA/ESI-MS evaluation of saffron (Crocus sativus L.) adulteration

The present study evaluated the reliability of the ISO/TS 3632-2 UV-Vis spectrometric method for saffron classification, making experiments on saffron samples to which were added increasing concentrations of common saffron spice adulterants (safflower, marigold and turmeric). The results showed that the ISO/TS 3632-2 method is not able to detect addition of up to 10-20%, w/w, of saffron adulterants. For additions from 20 to 50%, w/w, of the three adulterants, saffron was classified in a wrong category; addition of higher than 50%, w/w, determined variations in the investigated parameters that did not allow identification of the product as "saffron". In all cases, the method did not permit the recognition of the nature of the adulterant. On the contrary, the specificity of the HPLC/PDA/MS technique allowed the unequivocal identification of adulterant characteristic marker molecules that could be recognized by the values of absorbance and mass. The selection of characteristic ions of each marker molecule has revealed concentrations of up to 5%, w/w, for safflower and marigold and up to 2% for turmeric. In addition, the high dyeing power of turmeric allowed the determination of 2%, w/w, addition using exclusively the HPLC/PDA technique.     

Relativistic DFT calculations of the NMR properties and reactivity of transition metal methane σ-complexes: insights on C-H bond activation

Relativistic ZORA DFT methods have been employed to predict the NMR properties of methane and methyl hydride complexes of rhodium and iridium. Two of these compounds, the rhodium methane and the iridium methyl hydride complexes, have been recently characterized by NMR spectroscopy. Calculations reveal that relativistic effects are largely responsible of the high shielding observed for the proton and carbon resonances of the methane moiety. The key steps for the reaction mechanism of C-H cleavage catalyzed by both compounds have been investigated at the relativistic level. Although the structure of the intermediates and TSs for the Rh and Ir complexes is rather similar, subtle differences in the energetics are responsible of the different catalytic activity of the two complexes.     

Quantum field as a quantum cellular automaton: The Dirac free evolution in one dimension

We present a quantum cellular automaton model in one space-dimension which has the Dirac equation as emergent. This model, a discrete-time and causal unitary evolution of a lattice of quantum systems, is derived from the assumptions of homogeneity, parity and time-reversal invariance.     

Evaluation of N719 amount in TiO2 films for DSSC by thermogravimetric analysis

The aim of this work is to evaluate the amount of N719 dye in TiO₂ films for DSSCs by thermogravimetric analysis coupled with mass spectrometry (TG-MS) in comparison with the traditional method based on the dye extraction in NaOH solutions. The characterization was carried out on TiO₂ films applied on FTO glasses by automatic screen printing method. For all the samples, TG-MS showed three well defined steps. The first, below 100 °C and coupled to an endothermic signal was due to water release. From 200 to about 300 °C, there was the release of CO₂ coming from decarboxylation reaction of N719. The last exothermic step was due to the combustion of organic residues. As the decarboxylation reaction occurs with release of 4 moles of CO₂ per mole of N719, it was used to determine the dye loading of the samples that resulted in the range 7?15 wt% well agreeing the relevant content of dye obtained by desorption with NaOH.     

Nanostructure protein repellant amphiphilic copolymer coatings with optimized surface energy by Inductively Excited Low Pressure Plasma

Statistically designed amphiphilic copolymer coatings were deposited onto Thermanox, Si wafer, and quartz crystal microbalance (QCM) substrates via Plasma Enhanced Chemical Vapor Deposition of 1H,1H,2H,2H-perfluorodecyl acrylate and diethylene glycol vinyl ether in an Inductively Excited Low Pressure Plasma reactor. Plasma deposited amphiphilic coatings were characterized by Field Emission Scanning Electron Microscopy, X-ray Photoelectron Spectroscopy, Atomic Force Microscopy, and Water Contact Angle techniques. The surface energy of the coatings can be adjusted between 12 and 70 mJ/m(2). The roughness of the coatings can be tailored depending on the plasma mode used. A very smooth coating was deposited with a CW (continuous wave) power, whereas a rougher surface with R(a) in the range of 2 to 12 nm was deposited with the PW (pulsed wave) mode. The nanometer scale roughness of amphiphilic PFDA-co-DEGVE coatings was found to be in the range of the size of the two proteins namely BSA and lysozyme used to examine for the antifouling properties of the surfaces. The results show that the statistically designed surfaces, presenting a surface energy around 25 mJ/m(2), present no adhesion with respect to both proteins measured by QCM.     

Improved postharvest quality in patagonian squash (Cucurbita moschata) coated with radiation depolymerized chitosan

Different molecular weight chitosans were evaluated on the decay of coated Anquito squashes (Cucurbita moschata) as well as the maintenance of the fruit quality along five storage months. The original chitosan (Mw=391 kDa, 83% DD), was depolymerized by gamma radiation. Apart from chain scission, other chemical changes were not detected by FTIR or UV–vis analyses. The molecular weight characterization of chitosans was done by size exclusion chromatography with dual light scattering and concentration detection (SEC-MALLS-RI). The coating effectiveness was evaluated on the following parameters: fungal decay incidence, weight loss, firmness, total reducing sugar, soluble solid, flesh color, carotene content, pH and titratable acidity. No sign of fungal decay was observed in squashes coated with 122 and 56 kDa chitosans, which were also the most effective treatments in reducing the weight loss. The chitosan with Mw=122 kDa was also the best treatment considering firmness, internal aspect, sugar and carotene content. Then, radiation degraded chitosan was better in C. moschata preservation than the original chitosan.     

The Wehrl entropy has Gaussian optimizers

We determine the minimum Wehrl entropy among the quantum states with a given von Neumann entropy and prove that it is achieved by thermal Gaussian states. This result determines the relation between the von Neumann and the Wehrl entropies. The key idea is proving that the quantum-classical channel that associates with a quantum state its Husimi Q representation is asymptotically equivalent to the Gaussian quantum-limited amplifier with infinite amplification parameter. This equivalence also permits to determine the \(p\rightarrow q\) norms of the aforementioned quantum-classical channel in the two particular cases of one mode and \(p=q\) and prove that they are achieved by thermal Gaussian states. The same equivalence permits to prove that the Husimi Q representation of a one-mode passive state (i.e., a state diagonal in the Fock basis with eigenvalues decreasing as the energy increases) majorizes the Husimi Q representation of any other one-mode state with the same spectrum, i.e., it maximizes any convex functional.     

Parabens Permeation through Biological Membranes: A Comparative Study Using Franz Cell Diffusion System and Biomimetic Liquid Chromatography

Parabens (PBs) are used as preservatives to extend the shelf life of various foodstuffs, and pharmaceutical and cosmetic preparations. In this work, the membrane barrier passage potential of a subset of seven parabens, i.e., methyl-, ethyl-, propyl- isopropyl, butyl, isobutyl, and benzyl paraben, along with their parent compound, p-hydroxy benzoic acid, were studied. Thus, the Franz cell diffusion (FDC) method, biomimetic liquid chromatography (BLC), and in silico prediction were performed to evaluate the soundness of both describing their permeation through the skin. While BLC allowed the achievement of a full scale of affinity for membrane phospholipids of the PBs under research, the permeation of parabens through Franz diffusion cells having a carbon chain > ethyl could not be measured in a fully aqueous medium, i.e., permeation enhancer-free conditions. Our results support that BLC and in silico prediction alone can occasionally be misleading in the permeability potential assessment of these preservatives, emphasizing the need for a multi-technique and integrated experimental approach.