Furosemide is a potent high ceiling (loop) diuretic mainly used in the treatment of edematous states associated with cardiac, renal, and hepatic failure, and the treatment of hypertension. Furosemide has been classified as a class IV drug as per the biopharmaceutical classification system (BCS). D-Glucosamine HCl was used to increase the aqueous solubility of furosemide. The objective of the present work is to improve de dissolution profile of furosemide by formation of a physical mixture and a solid dispersion with D-glucosamine HCl. The solid dispersion was prepared by solvent method using acetone/water. The dissolution properties and physicochemical properties of furosemide: D-glucosamine HCl physical mixture and solid dispersion were investigated by dissolution test, X-ray diffractometry, infrared spectrometry, differential scanning calorimetry (DSC), microscopy (SEM) and 35 Cl Nuclear Quadrupole Resonance (NQR). The diuretic activity was proved comparing the solid dispersion with pure furosemide. This study shows that the dissolution rate of furosemide can be enhanced considerably by formulating it with D-glucosamine HCl, as a physical mixture or as a solid dispersion although cristallinity was maintained. Solid dispersion and pure furosemide showed significant increase in diuresis in rats as compared to the control group.

A thorough characterization of the γ, β, and glass phases of deuterated 1,1,2,2 tetrachloroethane (C2D2Cl4) via nuclear quadrupole resonance and Molecular Dynamic Simulations (MDSs) is reported. The presence of molecular reorientations was experimentally observed in the glass phase and in the β phase. In the β phase, and from MDS, these reorientations are attributed to two possible movements, i.e., a 180°  reorientation around the C2 molecular symmetry axis and a reorientation of the molecule between two non-equivalent positions. In the glass phase, the spin-lattice relaxation time T1 is of the order of 16 times lower than in the crystalline phase and varies as T(-1) below 100 K in good agreement with the strong quadrupolar relaxation observed in amorphous materials and in the glassy state of molecular organic systems. The activation energy of molecular reorientations in the glass phase (19 kJ/mol) is comparable to that observed in the glassy crystal of a "molecular cousin" compound, Freon 112 (C2F2Cl4), for the secondary β-relaxation. Moreover, the on-site orientational motion of tetrachloroethane molecules offers a new indirect evidence of the prominent role of such orientational disorder in glassy dynamics.

In this work we present experimental results that allow to characterize different solid modifications found in o-chlorohalobenzenes. Three disordered phases have been found in o-chlorobromobenzene. The stable phase at high temperature (phase I) is also obtained by quenching the sample at 77 K. Slow cooling allow to obtain the low temperature phase III which, on heating, transforms to phase II at 183 K and this, in turns, transforms to phase I at T~210 K. The disorder evidenced through the Nuclear Quadrupole Resonance spectra, is attributed to a random occupation of chlorine and bromine sites. In all phases there is evidence of molecular reorientations out of the benzene ring plane around the pseudo-symmetry axis between the atoms of Cl and Br. In o-chlorofluorobenzene two phases have been found depending on the cooling rate. One phase is disordered due to the random exchange of the occupation of Cl and F sites. In this case, there is also evidence of molecular reorientations out of the benzene ring plane, but in this case the reorientation is around the pseudo-symmetry axis that pass through the C-Cl bonds. Comparisons with the behavior of o-dichlorobenzene are also made.

Polymorphism is of widespread occurrence in the world of molecular crystals. In this work we present experimental results showing the existence of four solid phases in m-chlorofluorobenzene. A glass structure is achieved by quenching the liquid phase at 77K. This glassy state crystallizes in a disordered phase at T∼143K, which in turn transforms to the high-temperature stable phase (phase I) at T∼153K. Depending on the thermal history of the sample, a different ordered phase (phase III) can be obtained. The disorder is attributed to a molecular orientational disorder. There is no evidence of molecular reorientation in any phase. A study of the disorder-order phase transformation kinetics, using nuclear quadrupole resonance, is presented. The results are analyzed following Cahn's theory. Nucleation seems to take place at grain boundaries. Growth rates for different temperatures have been determined.

Pharmaceuticals can exist in many solid forms, which can have different physical and chemical properties. These solid forms include polymorphs, solvates, amorphous, and hydrates. Particularly, hydration process can be quite common since pharmaceutical solids can be in contact with water during manufacturing process and can also be exposed to water during storage. In the present work, it is proved that NQR technique is capable of detecting different hydrated forms not only in the pure raw material but also in the final product (tablets), being in this way a useful technique for quality control. This technique was also used to study the dehydration process from pentahydrate to trihydrate.

A spin decoupling method in nuclear quadrupole resonance spin echo experiment is used to detect the proton magnetic resonance absorption spectrum. The behavior of proton resonance in α phase of polycrystalline p-dichlorobenzene as a function of the intensity of the proton decoupling oscillating field (H2) is measured. Good agreement between the experimental resonance frequency and Shirley’s theory for a non-interacting 1/2 spin system is observed. To our knowledge this is the first time the NMR proton frequency dependence on linear polarized excitation field intensity for H2/Ho as high as 1.8 is measured.

Solid-state physical characterization of a pharmaceutical substance is necessary for successful development and approval of the final product. Different physical analytical techniques are available to do so: X-ray diffraction (XRD), IR, Raman, DSC, TG and NMR. Moreover, all of them detect the presence of excipients perturbing the analysis of the pure substance in low doses. In order to study polymorphism and pseudo polymorphism of drug, this paper introduces possible applications of pure nuclear quadrupole resonance, as a non-destructive technique in qualitative and quantitative approaches. Chlorpropamide and diclofenac sodium were used as examples. Unlike the mentioned techniques, the nuclear quadrupole resonance (NQR) signal of pharmaceutical compounds is not perturbed by the presence of solid excipient or other substances unless they possess resonance frequencies in the same frequency range of the compound studied.

p-chlorobromobenzene (PCBB) and p-chloroiodobenzene (PCIB) crystallize in the centrosymmetric space group P21/c, Z=2. Since the molecules do not possess an inversion center, the crystals exhibit orientational disorder, in other words, the electrical dipoles of regularly distributed molecules irregularly point in opposite directions. In this study, the temperature dependence of the nuclear quadrupole resonance (NQR) line shape for PCBB and PCIB and the spin-lattice relaxation time (T1) for PCIB have been measured. Both compounds exhibit an inhomogeneously broadened spectrum, as is expected for this kind of disorder. However, the measured NQR profile strongly depends on temperature, particularly that of PCIB. To explain this behavior, each orientation of the molecular dipoles has been considered as a component of what we call a binary orientational alloy. Within this framework it is shown that the minimum free energy of the system always corresponds to a centrosymmetric array, but that short-range orientational correlations may arise, depending on the difference in binding energy between a parallel and an antiparallel pair of neighboring molecules. In this way, the overall temperature dependence of the experimental profile can be succesfully reproduced if a one-dimensional orientational correlation among molecules is considered. At high temperatures, 180° molecular reorientations completely destroy the short range order and the measured spectra can be reproduced in terms of a pure random disordered model. The presence of molecular reorientations has been inferred from the measured temperature dependence of the nuclear spin-lattice relaxation time. In addition, the effect of short-range orientational correlations on T1(T) has also been calculated and discussed.

A pulsed NQR study of 4,4' dichlorobenzophenone has been performed to get information about dynamic features in its three crystalline phases. The authors found in phases I (T>190 K) and III (T<180 K) a normal thermal behaviour of the NQR frequency and spin-lattice relaxation time. In the intermediate phase II (180 K<T<190 K) the behaviour of the NQR parameters could not be explained with a simple Bayer's model of molecular torsional oscillations. This phase has been previously studied and is a nearly incommensurate one. Furthermore, a thermal hysteresis has been observed in both phase transition temperatures. this thermal hysteresis and the temperature range of the intermediate phase II showed a strong impurity concentration dependence.

Pulsed nuclear quadrupole resonance (NQR) measurements of $^{35}\mathrm{Cl}$ nuclei were performed on 43.5 mol % chlorobenzene solution in pyridine (a) in glassy state (${\mathit{T}}_{\mathit{g}}$=131 K) after quenching in liquid nitrogen and (b) in crystalline precipitate under slow cooling starting from liquid phase. In both cases the NQR line shape, obtained by the fast Fourier transform (FFT) method, consisted of a structure of two peaks, interpreted as contributions of two nonequivalent $^{35}\mathrm{nucleus}$ sites. A theoretical model is proposed for the line-shape analysis and the best-fit parameters yield excellent agreement with experimental spectra. It is suggested that the nonequivalent sites consist of nearly parallel and antiparallel alignment of chlorobenzene and pyridine molecules and that the line-broadening mechanism is due to a random distribution of angular displacements from these positions. Our data are in agreement with Goldstein studies of molecular-relaxation processes related to the changes observed on physical properties of amorphous materials at ${\mathit{T}}_{\mathit{g}}$.

Abstract Pulsed NQR has been used to get information about the two phase transitions (PT) in 4,4'-di-chlorobenzophenone. The measurements of the NQR spectrum and spin-lattice relaxation suggest that the PT's correspond to a normal-incommensurate and to the lock-in of a commensurate structure at lower temperature. Strong hysteresis has been observed, which could be assigned to memory effects produced by defect migrations.

Pulsed nuclear quadrupole resonance (NQR) has been used to get information about the nature of the molecular dynamics in two crystalline phases of 4,4'-dichlorobiphenyl sulphone. This work includes detailed experimental measurements of the NQR frequency, spin-lattice relaxation time, and line intensity temperature behavior in the range of temperature where a possible normal-to-incommensurate phase transition occurs. The experimental results show the existence of strong precursor effects to the normal-incommensurate phase transition within the range 185--140 K.

The molecular structure of 2,4,5-trichlorobenzenesulfonyl chloride has been determined by X-ray diffraction methods. The compound is orthorhombic,Aba2, witha=16.253(12),b=17.016(9),c=7.146(5) Å,V=1976(5) Å3,Z=8,D=1.88 kg·mm−3, (MoKα)=0.7107 Å,μ=136.8 cm−1,F(000)=1104. Data were obtained at room temperature; the finalR is 0.029 for 854 independent reflections. The substituted benzene ring is planar within experimental accuracy, the dihedral angle with the C(1)-S(1)-Cl(1) plane being 66.0(5)°. The compound has normal bond lengths and angles; some short intramolecular distances account for the maintenance of the rigid benzene frame. No significatively short intermolecular distances have been found. Confirmation of the oscillatory character of the semiexternal molecular motions operating above 180 K is accounted for.

Pulsed NQR spectroscopy was used to search for a structural phase transition from a normal to an incommensurate phase and others in 4,4′-dichlorobiphenyl sulphone. The experimental results show the existence of a structural phase transition to an incommensurate phase at 150 K and another transition to a possible commensurate phase at 110 K.

physica status solidi (a)Volume 91, Issue 2 p. K97-K99 Short Note Possible Incommensurate Structure in 4,4′-Dichlorobiphenyl Sulphone as Studied by the 35Cl Nuclei NQR† J. Corbero, J. Corbero Facultad de Matemática, Astronía y Física, Universidad Nacional de Córdoba Search for more papers by this authorD. J. Pusiol, D. J. Pusiol Facultad de Matemática, Astronía y Física, Universidad Nacional de Córdoba Consejo Nacional de Investigaciones Científicas y TécnicasSearch for more papers by this authorA. E. Wolfenson, A. E. Wolfenson Consejo Nacional de Investigaciones Científicas y TécnicasSearch for more papers by this authorA. H. Brunetti, A. H. Brunetti Facultad de Matemática, Astronía y Física, Universidad Nacional de Córdoba Consejo Nacional de Investigaciones Científicas y TécnicasSearch for more papers by this author J. Corbero, J. Corbero Facultad de Matemática, Astronía y Física, Universidad Nacional de Córdoba Search for more papers by this authorD. J. Pusiol, D. J. Pusiol Facultad de Matemática, Astronía y Física, Universidad Nacional de Córdoba Consejo Nacional de Investigaciones Científicas y TécnicasSearch for more papers by this authorA. E. Wolfenson, A. E. Wolfenson Consejo Nacional de Investigaciones Científicas y TécnicasSearch for more papers by this authorA. H. Brunetti, A. H. Brunetti Facultad de Matemática, Astronía y Física, Universidad Nacional de Córdoba Consejo Nacional de Investigaciones Científicas y TécnicasSearch for more papers by this author First published: 16 October 1985 https://doi.org/10.1002/pssa.2210910248Citations: 15 † Dedicated to Prof. Dr. Dr. h. c. Dr. E. h. P. GÖRLICH on the occasion of his 80th birthday ‡ Laprida 854, 5000 Córdoba, Argentina. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume91, Issue216 October 1985Pages K97-K99 RelatedInformation