A novel rapid quantitative analysis of drug migration on tablets using laser induced breakdown spectroscopy

There have been few reports wherein drug migration from the interior to the surface of a tablet has been analyzed quantitatively until now. In this paper, we propose a novel, rapid, quantitative analysis of drug migration in tablets using laser induced breakdown spectroscopy (LIBS). To evaluate drug migration, model tablets containing nicardipine hydrochloride as active pharmaceutical ingredient (API) were prepared by a conventional wet granulation method. Since the color of this API is pale yellow and all excipients are white, we can observe the degree of drug migration by visual inspection in these model tablets. In order to prepare tablets with different degrees of drug migration, the temperature of the drying process after tableting was varied between 50 to 80 °C. Using these manifold tablets, visual inspection, Fourier transform (FT)-IR mapping and LIBS analysis were carried out to evaluate the drug migration in the tablets. While drug migration could be observed using all methods, only LIBS analysis could provide quantitative analysis wherein the average LIBS intensity was correlated with the degree of drug migration obtained from the drying temperature. Moreover, in this work, we compared the sample preparation, data analysis process and measurement time for visual inspection, FT-IR mapping and LIBS analysis. The results of the comparison between these methods demonstrated that LIBS analysis is the simplest and the fastest method for migration monitoring. From the results obtained, we conclude that LIBS analysis is one of most useful process analytical technology (PAT) tools to solve the universal migration problem.     

Single walled carbon nanotube length determination by asymmetrical-flow field-flow fractionation hyphenated to multi-angle laser-light scattering

Asymmetrical flow field-flow fractionation (AFlFFF) hyphenated to multi-angle laser-light scattering (MALS) was evaluated in order to determine single walled carbon nanotube (SWCNT) length distribution. Fractionation conditions were investigated by examining mobile phase ionic strength and pH, channel components and cross-flow rate. Ammonium nitrate-based mobile phase with 10(-5)molL(-1) ionic strength and pH 6 allows the highest sample recovery (89±3%) to be obtained and the lowest loss of the longest SWCNT. A cross-flow rate of 0.9mLmin(-1) leads to avoid any significant membrane-sample interaction. Length was evaluated from gyration radius measured by MALS by comparing SWCNT to prolate ellipsoid. In order to validate the fractionation and the length determination obtained by AFlFFF-MALS, different SWCNT aliquots were collected after fractionation and measured by dynamic light scattering (DLS). AFlFFF is confirmed to operate in normal mode over 100-2000nm length. MALS length determination after fractionation is found to be accurate with 5% RSD. Additionally, a shape analysis was performed by combining gyration and hydrodynamic radii.     

The Weierstrass Subgroup of a Curve has Maximal Rank

We show that the Weierstrass points of the generic curve ofgenus g over an algebraically closed field of characteristic0 generate a group of maximal rank in the Jacobian. 2000 MathematicsSubject Classification 11G30, 14H40, 14H10, 14H55, 14Q05.     

Study of the Lithiated Phenylacetonitrile Monoanions and Dianions Formed According to the Lithiated Base Used (LHMDS, LDA, or n-BuLi). 2. Alkylation and Deuteriation Mechanism Study by Vibrational and NMR Spectroscopy and Quantum Chemistry Calculations

Mechanisms of alkylation by PhCH(2)Cl or CH(3)I in THF and of deuteriation by DCl (4 N in D(2)O) in THF or THF-toluene of lithiated phenylacetonitrile monoanions and dianions obtained with LHMDS, LDA, or n-BuLi are studied by vibrational and NMR spectroscopy and quantum chemistry calculations. Dialkylation of the three dilithio dianions generated with n-BuLi (2.0-2.7 equiv, THF-hexane) depends on their structure: N-lithio (PhCCNLi)(-)Li(+) and (C,N)-dilithio PhCLiCNLi dianions afford PhCR(2)CN (R = PhCH(2), CH(3)) from the intermediate N-lithio monoalkylated monoanion PhCRCNLi 10; C-lithio dianion (PhCLiCN)(-)Li(+) leads to a carbenoid species, the C-lithio monoalkylated nitrile PhCLiRCN 11, which either eliminates carbene Ph-C?-R and different LiCN species or isomerizes to PhCRCNLi in the presence of LiX (X = Cl, I). Dialkylation or dideuteriation of monoanions (monomers, dimers, and heterodimers [PhCHCNLi·LiR'], R' = (SiMe(3))(2)N, (i-Pr)(2)N) obtained with LHMDS or LDA (2.4 equiv, THF) proceeds via a sequential mechanism involving monometalation-monoalkylation (or monodeuteriation) reactions. Some carbene and (LiCNLi)(+) are also observed, and explained by another mechanism implying the C-lithio monoalkylated monoanion PhCLiRCN 9 in the presence of LiX. These results show the ambiphilic behavior of PhCLiRCN as a carbenoid (11) or a carbanion (9) and the importance of LiX formed in situ in the first alkylation step.     

Novel access to 1,4-benzodiazepin-2-ones via the Buchwald reaction and application to the synthesis of novel heterocyclics

A new two step strategy for the preparation of 1,4-benzodiazepin-2-ones has been developed starting from the 2-halogenobenzophenone under Buchwald conditions (Pd(OAc)₂, XantPhos, Cs₂CO₃, dioxane 100 °C). This strategy has been extended to two 2-halogeno-3-benzoyl-azines (pyridines, pyridazines).     

Solid-state 17O NMR study of α-d-glucose: exploring new frontiers in isotopic labeling,sensitivity enhancement,and NMR crystallography

We report synthesis and solid-state ¹⁷O NMR characterization of α-d-glucose for which all six oxygen atoms are site-specifically ¹⁷O-labeled. Solid-state ¹⁷O NMR spectra were recorded for α-d-glucose/NaCl/H₂O (2/1/1) cocrystals under static and magic-angle-spinning (MAS) conditions at five moderate, high, and ultrahigh magnetic fields: 14.1, 16.4, 18.8, 21.1, and 35.2 T. Complete ¹⁷O chemical shift (CS) and quadrupolar coupling (QC) tensors were determined for each of the six oxygen-containing functional groups in α-d-glucose. Paramagnetic Cu(ii) doping was found to significantly shorten the spin–lattice relaxation times for both ¹H and ¹⁷O nuclei in these compounds. A combination of the paramagnetic Cu(ii) doping, new CPMAS CryoProbe technology, and apodization weighted sampling led to a sensitivity boost for solid-state ¹⁷O NMR by a factor of 6–8, which made it possible to acquire high-quality 2D ¹⁷O multiple-quantum (MQ) MAS spectra for carbohydrate compounds. The unprecedented spectral resolution offered by 2D ¹⁷O MQMAS spectra permitted detection of a key structural difference for a single hydrogen bond between two types of crystallographically distinct α-d-glucose molecules. This work represents the first case where all oxygen-containing functional groups in a carbohydrate molecule are site-specifically ¹⁷O-labeled and fully characterized by solid-state ¹⁷O NMR. Gauge Including Projector Augmented Waves (GIPAW) DFT calculations were performed to aid ¹⁷O and ¹³C NMR signal assignments for a complex crystal structure where there are six crystallographically distinct α-d-glucose molecules in the asymmetric unit.

We report the first “total synthesis” of ¹⁷O-labeled d-glucose and its solid-state ¹⁷O NMR characterization with unprecedented sensitivity and resolution.     

Longitudinal relaxation spectra of the transverse Ising model close to Tc

The correlative effects of the nature of the interaction and of the method of calculation on the shape of the longitudinal relaxation function (LRF) for the transverse Ising model are analysed. The LRF is calculated in two ways: (i) its continued fraction representation within the three pole approximation (TPA); and (ii) the resolution of kinetic equations derived for the correlation functions beyond the random phase approximation (RPA). The effects of the nature of the interaction on the LRF spectral characteristics are investigated using an interaction made of three variable contributions: uniaxial dipolar, isotropic infinite range and anisotropic nearest-neighbour interactions. Contrary to the TPA, the kinetic-equation-method (KEM) leads to LRF's exhibiting a three peak structure for every q-value except q = 0 (q = 0_⊥ if the interaction is of dipolar nature) whatever the interaction. The approximations underlying both methods are specified and discussed. Comments on recent neutron scattering experiments on Li Tb_pY_1-pF₄ by Youngblood et al. are made.     

Optimization of the separation of Vinca alkaloids by nonaqueous capillary electrophoresis

A rapid method for the determination of Vinca alkaloids by nonaqueous capillary electrophoresis with diode array detection has been developed. A group of 11 alkaloids (catharanthine, vinorelbine, anhydrovinblastine, vinflunine, vindoline, 4-O-deacetylvinorelbine, 4-O-deacetylvinflunine, vindesine, vinblastine, 4'-deoxy-20',20'-difluorovinblastine, vincristine) could be readily separated within 10 min. The compounds were separated using a capillary of 38 cm effective length, a running buffer composed of 50 mM ammonium acetate and 0.6 M acetic acid in a methanol-acetonitrile (75:25, v/v) mixture. A constant voltage of 25 kV with a ramp time of 1 min and a 344.7 x 10(3) Pa pressure, applied simultaneously to inlet and outlet buffer vials, were used during sample analysis. Five of these alkaloids were selected for optimization of the separation and for validation studies with respect to specificity, linearity, range, limits of quantification and detection and then accuracy. The feasibility of the assay was demonstrated by analyzing a commercial sample of vinorelbine (Navelbine, ampoule at 10 mg/ml of vinorelbine base). The results were compared with a high-performance liquid chromatography method.     

Crystal Structure of a p-Benzylcalix[5]arene- pyridine Complex

p-Benzylcalix[5]arene.3py (py = pyridine) (1) crystallizes in the triclinic space group P1, a = 10.641(3), b = 13.975(3), c = 24.052(12) Å, = 94.60(4), = 91.51(4), = 111.46(2)°, V = 3312(4) ų, Z = 2. Refinement led to a final conventional R value of 0.065 for 5457 reflections. The calixarene is in a distorted cone conformation. Two pyridine molecules are hydrogen bonded to phenolic oxygen atoms and one of them is included in the hydrophobic cavity of the neighboring calixarene molecule along the a axis.