Monohydrate Form Research Articles

Structural investigation of anhydrous nitrofurantion and its monohydrate based on terahertz/Raman vibrational spectroscopy and density functional theory

Anhydrous nitrofurantion and its monohydrated form were characterized and analyzed by using vibrational spectroscopic techniques including terahertz time-domain spectroscopy and Raman spectroscopy at room temperature. The experimental results indicate that both spectroscopic techniques could recognize the above two forms clearly. In terahertz spectra, anhydrous nitrofurantion has absorption peaks at 1.26 and 1.60 THz, while the monohydrated form has three peaks at 0.67, 1.05 and 1.50 THz respectively. Raman spectra also show some differences between the anhydrous nitrofurantion and monohydrated form, but not significant as that of terahertz spectra since Raman-active vibrational modes are mostly from intra-molecular interaction of various functional groups within molecules while terahertz spectra is more sensitive to inter-molecular interaction within various solid-state crystalline forms. Density functional theory was performed to simulate the optimized structures and vibrational modes of these two forms. In addition, the characteristic bands of anhydrous nitrofurantion and its monohydrate are also assigned based on the simulation results from the density functional theory calculation.

X-ray powder diffraction data for three red azo pigments: sodium, barium, and ammonium lithol salts

Lithol reds belong to the group of azo pigments, which were popular artists’ colouring materials in the first half of the twentieth century. These pigments were also used in many branches of industry. Here, we report X-ray powder diffraction data, unit-cell parameters, and space groups for three compounds from this group: sodium (E)-2-((2-hydroxynaphthalen-1-yl)diazenyl)naphthalene-1-sulphonate monohydrate (Na lithol red), monoclinic, space group C2/c, with cell parameters a = 33.343(7), b = 6.667(2), c = 16.397(4) Å, β = 90.83°, V = 3644.51 Å3, Z = 8; barium (E)-2-[(2-hydroxynaphthalen-1-yl)diazenyl]naphthalene-1-sulphonate trihydrate (Ba lithol red), monoclinic, space group P21/m, with cell parameters a = 17.758(9), b = 6.209(4), c = 16.857(8) Å, β = 92.07°, V = 1857.39 Å3, Z = 2; and ammonium (E)-2-[(2-hydroxynaphthalen-1-yl)diazenyl]naphthalene-1-sulphonate monohydrate (NH4 lithol red), monoclinic, space group P2/c, with cell parameters a = 17.721(5), b = 6.428(3), c = 16.911(5) Å, β = 100.31(3)°, V = 1895.31 Å3, and Z = 4. In the first and third cases we synthesised the pigments in their monohydrate form, performed X-ray powder diffraction measurements, and indexed all of the obtained diffraction maxima. In the case of the barium compound, despite many efforts in the course of the synthesis procedure, the powder diffraction patterns of the obtained samples were not of the best quality. Nevertheless, we indexed the best one and found a reliable space group and cell parameters.

Spectroscopic and structural studies of the diosmin monohydrate and anhydrous diosmin

Diosmin, a flavone glycoside frequently used in therapy of various veins diseases in monohydrate form, exhibits poor solubility in water and low bioavailability. Due to the fact that the anhydrous forms of drugs generally have better bioavailability than the corresponding hydrates, the aim of this study was to analyze the conversion of diosmin monohydrate (DSNM) to anhydrous diosmin (DSNA) that occurs upon heating. The mechanism of this transformation was examined as well as advanced structural studies of each form were performed using 13C CP/MAS SSNMR, DSC, FT-IR and PXRD techniques. Spectroscopic findings were supported by CASTEP-DFT calculations of NMR and IR parameters. The pathway of reversible transformation was specified as follows: DSNM upon heating for 24h at temperature up to 110°C losses non-crystalline water and converts into metastable form (DSNM*) that turns into DSNA during heating at temperature 140°C for next 24h. Under room temperature DSNA spontaneously absorbs moisture from air and turns into a DSNM within 72h. The detailed analysis of CP kinetic parameters (T1ρI) revealed presence of metastable, intermediate form of diosmin (DSNM*) and allowed its characterization. The results are essential for further studies comparing dissolution and bioavailability of DSNM and DSNA. The study provided an understanding of the conversion pathway of the diosmin monohydrate into its anhydrate form when it is exposed to increased temperature.

Experimental and Mechanistic Study of the Heterogeneous Nucleation and Epitaxy of Acetaminophen with Biocompatible Crystalline Substrates

The presence of different heterogeneous surfaces can directly influence the nucleation kinetics, crystal growth, and morphology of active pharmaceutical ingredients (APIs). However, a mechanistic understanding of heterogeneous nucleation remains lacking. Herein, we report the use of biocompatible crystalline heterogeneous surfaces to enhance the nucleation rates of the model API compound acetaminophen (APAP). We also report experimental and computational studies of the epitaxial growth mechanism of APAP on different substrates. Five crystalline substrates, namely, d-galactose (DGAL), the α and β forms of d-mannitol (DMAN), α-lactose monohydrate (LMH), and xylitol (XYL) were selected because they contain a similar functionality: a high density of hydroxyl groups per molecule. We measured the induction times in the presence of the substrates and used the results to rank the substrates based on their ability to enhance the nucleation of APAP. While all selected substrates enhanced the nucleation rates, XYL w...

Thermal properties of iopamidol

Three crystal forms of iopamidol, an iodinated contrast media used in radiology, have been so far elucidated: an anhydrous, a monohydrate and a pentahydrate form (labeled hereafter as W0, W1 and W5, respectively), which showed the occurrence of different conformations, atropisomeric in nature. Specifically, the anhydrous and monohydrate forms contain iopamidol with a “syn” conformation of the two symmetric sidearms, while an “anti” conformation was found in the pentahydrate, making it a conformational (pseudo)-polymorph of the first two. The three crystal forms have been here investigated by means of DSC, variable temperature X-ray powder diffraction and Raman spectroscopy. This study enabled us to highlight the thermal-induced transformations, leading to the discovery of new crystal forms, for a total of four hydrated and four distinct anhydrous phases. In particular, the DSC curve of W0 revealed only a reversible solid–solid transition at around 180 °C before melting, with subsequent degradation above 300 °C. W1, after the loss of lattice water around 100 °C, shows a characteristic split peak at about 250 °C, which is attributed to melting. Below 150 °C, powder diffraction of W1 suffers of minor changes, with a smooth variation of the lattice parameters, in agreement with a progressive loss of water in a reversible event, monitored also by DSC. At variance, W5 evidenced an irreversible loss of water in three distinct steps, for three, one and one H2O molecules each, respectively; subsequent transitions occur at 140 and 180 °C, before melting at 240 °C. Three clearly visible transformations were also detected by variable temperature powder diffraction measurements, where the loss of three molecules of water in a single step, generating a bis-hydrated species (W2), is followed by a second dehydration process leading, above 75 °C, to a new monohydrate phase W1′, different from the known W1 form. The Raman spectra of the three crystal forms, measured upon heating up to 160 °C, evidenced changes in spectral regions of amides that, according to our simulations of the vibrational properties, can be attributed to changes of the hydration properties and, more significantly, in terms of the “syn” and “anti” conformations.

Influence of Solution Composition and Temperature on the Crystal Form of Sodium Dehydroacetate

AbstractThe slurry transformation of sodium dehydroacetate monohydrate with different compositions of water and methanol was investigated. The water content and temperature did not only affect the solubility but also the crystal form of the precipitated material. A new needle hydrate form of sodium dehydroacetate appeared on the surface of the anhydrate when the water content was between 2 % and the critical transformation values which varied with temperature. The results revealed that the needle hydrate was a new form of sodium dehydroacetate monohydrate. A possible explanation for these observations was found in the relationship between the change of water content, the interaction between solute and solvent, and the influence of supersaturation.

Solid dispersions of Myricetin with enhanced solubility: Formulation, characterization and crystal structure of stability-impeding Myricetin monohydrate crystals

Three solid dispersion forms of Myricetin combined with the Polyvinylpyrrolidone were successfully prepared by spray drying method, and characterized by X-ray powder diffraction, thermal analysis, infrared spectroscopy and optical microscopy. Zeta potential measurements provided indications on solid dispersions stability in aqueous suspension related to their storage at elevated temperature and relative humidity, which depends on the Myricetin load. By increase of Myricetin load, the stability of the solid dispersion is impeded due to growth of Myricetin monohydrate crystals. The amorphous dispersions with 10% and 50% Myricetin load are stable and, compared to pure Myricetin, their aqueous solubility is enhanced by a factor of 47 and 13, respectively. The dispersion with 80% Myricetin load is unstable on storage, and this behavior acts in conjunction with the development of Myricetin monohydrate crystals. Single-crystal X-ray diffraction results obtained for Myricetin monohydrate reveal a structure of an infinite 2D network of hydrogen-bonded molecules involving all six hydroxyl groups of Myricetin. The water molecules are positioned in between the infinite chains, and contribute via H-bonds to robust crystal packing. The calculated needle-like morphology of monohydrate form is in agreement with the optical microscopy results. The study shows that the solid amorphous dispersions with up to 50% Myricetin load are a viable option for achieving substantial solubility improvement of Myricetin, and supports their potential use in pharmaceutical applications.

Lattice energetics and thermochemistry of acridine derivatives and substituted acridinium trifluoromethanesulphonates

The enthalpies and temperatures of melting of eight 9-substituted acridines (alkyl, aryl or alkoxy) (I) and six their 10-methylated-acridinium trifluoromethanesulphonate (II) derivatives were measured by DSC. The enthalpies and temperatures of volatilisation of the first group of compounds were also determined by DSC or obtained by fitting TG curves to the Clausius–Clapeyron relationship. By combining the enthalpies of formation of gaseous acridines or 10-methylacridinium trifluoromethanesulphonate ions, obtained by the DFT method, and the corresponding enthalpies of sublimation and/or crystal lattice enthalpies, the enthalpies of formation of the compounds in the solid phase were predicted. For compounds whose crystal structures are known, experimental enthalpies of sublimation correspond reasonably well to crystal lattice enthalpies predicted theoretically as the sum of electrostatic, dispersive and repulsive interactions. Analysis of crystal lattice enthalpy contributions indicates that dispersive interactions between molecules always predominate in the case of acridine derivatives, whilst the crystal lattices of their quaternary salts are stabilised by electrostatic interactions between ions. Only in the case of 9-bromomethylacridine derivative, which crystallises in the monohydrated form, electrostatic contribution to the crystal lattice energy is significantly higher than in the other investigated acridines.

Density functional study on the tautomerism of pyrano[2,3-d]pyrimidine derivative: intramolecular and intermolecular proton transfer

The proton transfer reaction mechanisms in the anhydrous and monohydrated forms of 7-amino-6-cyano-5-benzene-5H-pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones on the transition state structures have been carried out in the gas phase using the B3LYP density functional method. For the reaction, three possible mechanisms are considered and three pathways are subsequently discussed. Meanwhile, the assistant effects of water molecules in the 1st path, which is considered as the best way of proton transfer, have been discussed in detail with the number of water molecules increasing. Results reveal that water molecules hold a strong catalysis effect on the proton transfer, and the polar solvent is favorable to the stability of complexes.

Controlled Reactivity of 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene (DBU) in the Selective Synthesis of 1‐(Bromoethynyl)arenes

AbstractThe nucleophilic reactivity of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) was completely controlled by the formation of monohydrate (DBU⋅H2O) in the synthesis of 1‐(bromoethynyl)arenes from 1,1‐dibromoalkenes. Differential reactivity of DBU in protic solvents as compared to aprotic solvents has been explored to prevent the formation of mixtures of products in this reaction. Hydrated DBU is found to be superior to dry DBU, both for the selective synthesis and ease of isolation. In addition, use of DBU⋅H2O as a non‐nucleophilic mild base allowed us to synthesise 1‐(bromoethynyl)arenes via a reaction under solvent‐free conditions. Utilization of DBU⋅H2O as sole reagent also allowed us to isolate the products without column chromatographic purifications.magnified image

Synthesis and structure of heptaaqua{nitrilotris(methylenephosphonato)}(dibarium)sodium monohydrate [Na(H2O)3{μ6-NH(CH2PO3)3}(μ-H2O)3Ba2(H2O)] · H2O

Crystals of the monohydrate form of heptaaqua{nitrilotris(methylenephosphonato)}(dibarium) sodium [Na(H2O)3{µ6-NH(CH2PO3)3}(µ-H2O)3Ba2(H2O)] · H2O are obtained; space group P21/c, Z = 4; a = 13.9117(10) A, b = 11.54030(10) A, and c = 24.1784(17) A, s = 148.785(18)°. The Na atom is coordinated octahedrally by one oxygen atom of a phosphonate group and five water molecules, including two bridging molecules. Ba atoms occupy two inequivalent crystallographic positions with coordination number eight and nine. The coordination spheres of both Ba atoms include two water molecules. Each ligand is bound to one Na atom and five Ba atoms forming three Ba–O–P–O and five Ba–O–P–C–N–C–P–O chelate cycles. In addition to the coordination bonds, molecules, including the solvate water molecule, are involved in hydrogen bonds in the crystal packing.

Plasma Creatine Kinetics After Ingestion of Microencapsulated Creatine Monohydrate with Enhanced Stability in Aqueous Solutions

ABSTRACTCreatine monohydrate represents one of the largest sports supplement markets. Enhancing creatine (CRE) stability in aqueous solutions, such as with microencapsulation, represents innovation potential. Ten physically active male volunteers were randomly assigned in a double-blind design to either placebo (PLA) (3-g maltodextrin; n = 5) or microencapsulated CRE (3-g creatine monohydrate; n = 5) conditions. Experimental conditions involved ingestion of the samples in a 70-mL ready-to-drink format. CRE was delivered in a novel microencapsulation matrix material consisting entirely of hydrolyzed milk protein. Three hours after ingestion, plasma creatine concentrations were unchanged during PLA, and averaged ∼45 μM. During CRE, plasma creatine concentration peaked after 30 min at 101.6 ± 14.9 μM (p < 0.05), representing a 2.3-fold increase over PLA. Thereafter, plasma creatine concentration gradually trended downwards but remained significantly elevated (∼50% above resting levels) 3 hr after ingestion. These results demonstrate that the microencapsulated form of creatine monohydrate reported herein remains bioavailable when delivered in aqueous conditions, and has potential utility in ready-to-drink formulations for creatine supplementation.

Myelography Iodinated Contrast Media. 2. Conformational Versatility of Iopamidol in the Solid State.

The phenomenon of polymorphism is of great relevance in pharmaceutics, since different polymorphs have different physicochemical properties, e.g., solubility, hence, bioavailability. Coupling diffractometric and spectroscopic experiments with thermodynamic analysis and computational work opens to a methodological approach which provides information on both structure and dynamics in the solid as well as in solution. The present work reports on the conformational changes in crystalline iopamidol, which is characterized by atropisomerism, a phenomenon that influences both the solution properties and the distinct crystal phases. The conformation of iopamidol is discussed for three different crystal phases. In the anhydrous and monohydrate crystal forms, iopamidol molecules display a syn conformation of the long branches stemming out from the triiodobenzene ring, while in the pentahydrate phase the anti conformation is found. IR and Raman spectroscopic studies carried out on the three crystal forms, jointly with quantum chemical computations, revealed that the markedly different spectral features can be specifically attributed to the different molecular conformations. Our results on the conformational versatility of iopamidol in different crystalline phases, linking structural and spectroscopic evidence for the solution state and the solid forms, provide a definite protocol for grasping the signals that can be taken as conformational markers. This is the first step for understanding the crystallization mechanism occurring in supersaturated solution of iopamidol molecules.

Unveiling multiple solid-state transitions in pharmaceutical solid dosage forms using multi-series hyperspectral imaging and different curve resolution approaches

Solid-state transitions at the surface of pharmaceutical solid dosage forms (SDF) were monitored using multi-series hyperspectral imaging (HSI) along with Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS) and Parallel Factor Analysis (PARAFAC and PARAFAC2). First, the solid-state transformation due to the dehydration of the monohydrate forms of piroxicam and lactose to their respective anhydrate counterparts in tablets were monitored using temperature series NIR-HSI. PARAFAC and MCR-ALS solutions were hampered by the lack of strict trilinearity of the pixels among the unfolded series NIR-images (three-way array) and due to rotational ambiguity (augmented matrix), respectively, while PARAFAC2 resolved satisfactorily the profile of the corresponding compounds in the pixels in the series NIR-images. Next, the amorphous-to-crystalline transitions were monitored in solid dispersion of indomethacin with polyvinylpyrrolidone using time series MIR-HSI. MCR-ALS properly resolved the known solid-state forms of the drug in the pixels of the series MIR-images, while PARAFAC and PARAFAC2 failed to properly resolve all the drug forms in the series MIR-images due to i) strict trilinearity leak in the three-way array and ii) the mandatory constant cross-product AkTAk over the k series MIR-images (A is the loadings of the shift mode), respectively. The highlighting of the advantages and limitation of the corresponding curve resolution methods stressed their potential applicability when handling multi-series HSI to study solid-state transitions in pharmaceutical SDFs.

Hydrogen-bonding synthons in lamotrigine salts: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium 2-[(2-carboxyphenyl)disulfanyl]benzoate in its monohydrate and anhydrous forms.

Lamotrigine is a drug used in the treatment of epilepsy and related convulsive diseases. The drug in its free form is rather inadequate for pharmacological use due to poor absorption by the patient, which limits its bioavailability. On the other hand, the lamotrigine molecule is an excellent hydrogen-bonding agent and this has been exploited intensively in the search for better formulations. The formulation presently commercialized (under the brand name Lamictal) is rather complex and includes a number of anions in addition to the active pharmaceutical ingredient (API). The title salts of lamotrigine, namely 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium 2-[(2-carboxyphenyl)disulfanyl]benzoate monohydrate, C9H8Cl2N5+·C14H9O4S2-·H2O, (I), and the anhydrate, C9H8Cl2N5+·C14H9O4S2-, (II), contain a lamotriginium cation (L), a hydrogen dithiodibenzoate monoanion (D) and, in the case of (I), a disordered solvent water molecule. Both L and D present their usual configurations severely twisted around their central C-C and S-S bonds, respectively. The supramolecular structure generated by the many available donor and acceptor sites is characterized by a planar antisymmetric motif of the form D-L-L-D, i.e. the structural building block. Although this characteristic motif is extremely similar in both structures, its conformation involves different donors and acceptors in its R22(8) central L-L homosynthon. The lateral R22(8) D-L heterosynthons are, on the other hand, identical. These substructures are further connected by strong hydrogen bonds into broad two-dimensional structures, in turn weakly linked to each other. Even if the homo- and heterosynthons in (I) and (II) are rather frequent in lamotrigine structural chemistry, the composite tetrameric synthon appears to be much less common. The occurrence of these motifs among lamotrigine salts and cocrystals is analyzed.

Comparing of the crystal structure and spectroscopic properties of some stilbazolium dyes with enlarged π-conjugated system I. Chromophores with p-dimethylamino group

A comparative study of the structures and spectroscopic properties of two styrylquinolinium dyes: 4-{(E)-2-[4-(dimethylamino)naphthalen-1-yl]ethenyl}-1-methylquinolinium iodide in an anhydrous (Structure I), and monohydrate (Strucuture II) forms and the newly synthesized dye 4-{(E)-2-[4-(dimethylamino)naphthalen-1-yl]ethenyl}-1-pentylquinolinium bromide dihydrate (III) has been conducted by single crystal X-ray diffraction, IR- and Raman spectroscopy, UV–Vis, steady-state and time-resolved fluorescence spectroscopy, 1H and 13C NMR spectroscopy, and TG/DTA analyses. The structures I, II and III belong to a monoclinic system, space groups P21/c, P21/n, and C2/c, respectively. In all of the crystal structures the molecules in the asymmetric unit are in an E configuration and the naphthyl and quinolinium aromatic rings are nearly planar. The angle between the mean planes of the aromatic rings is in the range 1.43–3.65°. Calculated BLA (Bond Lengths Alternation) parameters are close to the optimal. Solvatochromism in 12 organic solvents has been investigated by using absorption and emission spectroscopy. Reversal in solvatochromic behavior of the absorption spectra has been observed. The data in solutions indicate a significant charge transfer (CT) band shifting up to 84 nm, corresponding to a great molecular first hyperpolarizability values, and very large Stokes shift up to 245 nm. The average lifetime of the fluorescence of the dye III, determined from the measured data by multi-order exponential decay curve fitting as 34.71 ns in benzene and 2.98 ns in DMSO.

Relative bioavailability of copper in tribasic copper chloride to copper in copper sulfate for laying hens based on egg yolk and feather copper concentrations

This experiment was conducted to determine the relative bioavailability (RBV) of Cu in tribasic copper chloride (TBCC) to Cu in copper sulfate (monohydrate form; CuSO4·H2 O) for layer diets based on egg yolk and feather Cu concentrations. A total of 252, 72-wk-old Hy-Line Brown laying hens were allotted to 1 of 7 treatments with 6 replicates consisting of 6 hens per replicate in a completely randomized design. Hens were fed corn-soybean meal-based basal diets supplemented with 0 (basal), 100, 200, or 300 mg/kg Cu from CuSO4 or TBCC for 4 wk. Results indicated that egg production, egg weight, and egg mass were not affected by dietary treatments. However, increasing inclusion levels of Cu in diets from CuSO4 decreased (P < 0.05) feed conversion ratio (FCR), whereas increasing inclusion levels of Cu in diets from TBCC did not affect FCR, indicating significant interaction (P < 0.05). Increasing inclusion levels of Cu from TBCC or CuSO4 increased (P < 0.05) Cu concentrations of egg yolk and feathers. Feather Cu concentrations were greater (P < 0.01) for hens fed diets containing CuSO4 than for hens fed diets containing TBCC. The values for the RBV of Cu in TBCC to Cu in CuSO4 based on log10 transformed egg yolk and feather Cu concentrations were 107.4% and 69.5%, respectively. These values for the RBV of Cu in TBCC did not differ from Cu in CuSO4 (100%). The RBV measured in egg yolk did not differ from the RBV measured in feather. In conclusion, the RBV of Cu in TBCC to Cu in CuSO4 can be determined using Cu concentrations of egg yolk and feathers although the values depend largely on target tissues of laying hens. For a practical application, however, the RBV value of Cu in TBCC to Cu in CuSO4 could be 88.5% when the RBV values determined using egg yolk and feather Cu concentrations were averaged.

Comprehensive morpho-constitutional analysis of urinary stones improves etiological diagnosis and therapeutic strategy of nephrolithiasis

The generalized use of physical methods, X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) decisively improved urinary stone analysis by allowing to accurately identify the chemical nature, crystalline phases and relative proportions of stone constituents. Such compositional analysis is sufficient to identify stone diseases involving a single specific component such as cystine, 2,8-dihydroxyadenine (DHA), struvite, uric acid, ammonium hydrogen urate or a drug. However, for common calcium nephrolithiasis, which represents by far the largest part of urinary stones throughout the world, the simple identification of calcium oxalate (CaOx) and/or calcium phosphate (CaP) as constituents provides incomplete etiologic information because a same elemental stone composition may result from different lithogenic processes. A more comprehensive method combining careful morphologic examination of the surface and the section of stones with detailed FTIR analysis of the nature, location, crystalline phases and a respective proportion of stone constituents, therefore termed ‘morpho-constitutional’ analysis, as used in our laboratory for four decades provides more complete etiologic information. In common idiopathic CaOx nephrolithiasis, the predominance of the monohydrate form (COM) was shown to be associated with elevated urine Ox concentration, whereas the dihydrate form (COD) was associated with hypercalciuria, thus orienting dietary and/or pharmacological intervention. A major contribution of the method is to immediately orient the diagnosis of rare, but severe, diseases leading to a loss of renal function, when stone analysis reveals a peculiar morphology of common constituents. The most salient examples are the type Ic morphology of COM stones, pathognomonic of primary hyperoxaluria, type Ie morphology, which is highly suggestive of absorptive hyperoxaluria as seen in inflammatory bowel diseases and pathologies inducing steatorrhea, type IIId morphology of ammonium urate stones, which orientates towards chronic diarrhea with dietary imbalance and loss of electrolytes, and type IVa2 morphology of carbapatite, specific of distal renal tubular acidosis of congenital or acquired origin, and distinctive aspect of 2,8-DHA stones. In conclusion, the proposed morpho-constitutional method should be recommended for routine stone analysis, inasmuch as it is simple, rapid, reliable, clinically relevant and cost-effective.

Crystalluria analysis improves significantly etiologic diagnosis and therapeutic monitoring of nephrolithiasis

The search for crystalluria and morphologic analysis of urinary crystals is of interest in the diagnostic evaluation and assessment of efficacy of therapeutic strategies in stone formers. In common calcium oxalate (CaOx) nephrolithiasis, identification of the monohydrate or dihydrate form of CaOx orients toward hyperoxaluria or hypercalciuria as the main lithogenic mechanism, respectively. An unusual high abundance of crystals exclusively made of CaOx monohydrate is highly suggestive of primary hyperoxaluria, the most severe of all types of renal stone diseases. The identification of crystal species such as struvite, cystine, 2,8-dihydroxyadenine, which are not found in normal urine, is indicative of specific pathological conditions, namely, infection stones and hereditary diseases such as cystinuria and dihydroxyadeninuria. Such diseases expose to progressive loss of renal function unless they are prevented by specific therapeutic measures. The presence of crystals made of drugs may entail the risk of kidney dysfunction because of crystallization of the drug or its metabolites. Serial determination of crystalluria, which reflects the activity of stone disease and its response to therapeutic measures, is of major interest in the follow-up of patients suffering from nephrolithiasis. It should be more largely used in clinical practice in most stone formers, still more for the surveillance of patients affected by severe, hereditary renal stone diseases such as primary hyperoxaluria, cystinuria, and dihydroxyadeninuria, where determination of the global crystal volume allows assessing the efficacy of therapeutic measures and optimizing the medical management of the patients.

Acoustic emission during the solvent mediated cooling crystallization of citric acid

The potential of Acoustic Emission (AE) for controlling crystallization processes is investigated. The sensing technology is successfully applied to monitor the batch cooling crystallization of citric acid (CA) in water. The solvent-mediated phase transition between the anhydrous and the monohydrated forms of CA is clearly detected from the recorded acoustic measurements. A tremendous amount of acoustic data is recorded by the equipment, and the analysis of the data is focused on the evaluation of AE as a new sensor for monitoring the basic steps of the crystallization processes (i.e., nucleation, growth, phase transition, etc.) A time- and frequency-domain analysis is presented which shows the wealth of the technique. It is finally concluded that AE allows very early detection of nucleation events, provides a means of monitoring the development of the crystallization process and allows monitoring phase transition phenomena obtained through cooling. It is thus suggested that acoustic emission could be valuable in the development of new crystallization monitoring and control strategies: this is all the more interesting that the acoustic piezo-sensor is non-intrusive and does not require any sampling of the slurry, two features which are of tremendous importance in the field of cooling crystallization processes.