Hydrochloride Monohydrate Research Articles

New Solid Forms of the Antiviral Drug Arbidol: Crystal Structures, Thermodynamic Stability, and Solubility.

Salts of the antiviral drug Arbidol (umifenovir) with pharmaceutically relevant benzoate and salicylate anions were obtained, and their crystal structures were described. For Arbidol salicylate, an unstable solvate with acetonitrile was also found and characterized. Analysis of the conformational preferences of the Arbidol molecule in the crystal structures showed that it adopts two types of conformations, namely "open" and "closed", both of which correspond to local conformational energy minima of the isolated molecule. Thermal stability of the Arbidol salicylate solvates with chloroform and acetonitrile was analyzed by means of differential scanning calorimetry and thermogravimetric analysis. The standard thermodynamic functions of the salt formation were determined. The Gibbs energy change of the process was found to be negative, indicating that the formation of the salts from individual components is a spontaneous process. The dissolution study of the Arbidol salts performed in aqueous buffer solutions with pH 1.2 and 6.8 showed that both salts dissolve incongruently to form an Arbidol hydrochloride monohydrate at pH 1.2 and an Arbidol base at pH 6.8, respectively.

High-resolution NMR of hydrogen in organic solids by DNP enhanced natural abundance deuterium spectroscopy

We demonstrate that high field (9.4T) dynamic nuclear polarization (DNP) at cryogenic (∼100K) sample temperatures enables the rapid acquisition of natural abundance 1H–2H cross-polarization magic angle spinning (CPMAS) solid-state NMR spectra of organic solids. Spectra were obtained by impregnating substrates with a solution of the stable DNP polarizing agent TEKPol in tetrachloroethane. Tetrachloroethane is a non-solvent for the solids, and the unmodified substrates are then polarized through spin diffusion. High quality natural abundance 2H CPMAS spectra of histidine hydrochloride monohydrate, glycylglycine and theophylline were acquired in less than 2h, providing direct access to hydrogen chemical shifts and quadrupolar couplings. The spectral resolution of the 2H solid-state NMR spectra is comparable to that of 1H spectra obtained with state of the art homonuclear decoupling techniques.

Growth and Characterization of Non-Linear Optical Single Crystal: L-cysteine Hydrochloride Monohydrate

Growth and Characterization of Non-Linear Optical Single Crystal: L-cysteine Hydrochloride Monohydrate

Crystal structure of ziprasidone hydrochloride monohydrate, C21H22Cl2N4OS(H2O)

The crystal structure of ziprasidone hydrochloride monohydrate has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Ziprasidone hydrochloride monohydrate crystallizes in space groupP-1 (#2) witha= 7.250 10(3),b= 10.986 66(8),c= 14.071 87(14) Å,α= 83.4310(4),β= 80.5931(6),γ= 87.1437(6)°,V= 1098.00(1) Å3, andZ= 2. The ziprasidone conformation in the solid state is very close to the minimum energy conformation. The positively-charged nitrogen in the ziprasidone makes a strong hydrogen bond with the chloride anion. The water molecule makes two weaker bonds to the chloride, and acts as an acceptor in an N–H⋯O hydrogen bond. The powder pattern is included in the Powder Diffraction File™as entry 00-064-1492.

Unidirectional growth of large size urea doped l-cysteine hydrochloride monohydrate NLO organic crystal and investigations of its crystalline and optical properties

Organic crystals of urea doped l-cysteine hydrochloride monohydrate have been grown by unidirectional solution growth technique. The crystal grown by this technique has high growth rate as compared to the crystals grown using conventional slow cooling method. This method is ideally suited to grow crystals along a specific direction. The growth process was monitored at regular intervals of time in a time-lapsed manner to estimate the growth rate and also monitor its quality visually. The grown crystal was subjected to different characterizations in order to confirm the phase of the grown crystal, its crystalline perfection and optical properties. The X-ray diffraction confirmed the phase of the crystal. The rocking curve recorded using high resolution X-ray diffraction (HRXRD) technique reveals that the crystal grown using conventional slow cooling method has internal gain boundaries whereas that grown by unidirectional technique has high degree of crystalline perfection. The bonding environment present in the crystal was characterized by FTIR spectroscopy where vibrational frequencies of the different functional groups present were identified. The optical quality of the crystal was characterized using UV–vis-NIR spectrophotometer and Mach–Zehnder interferometer. The nonlinear optical response of the crystal was measured using Kurtz–Perry method and found to be 1.4 times that of a KDP crystal.

Synthesis and characterization of a novel hollow nanoparticle-based SnS crystal product with microcluster-like 3D network hierarchitectures

SnS is an important semiconductor and its performance depends greatly on its morphology and 3D architecture. So the synthesis for it with specific structures has been widely paid attention. Herein, a novel hollow nanoparticle-based SnS crystal product with microcluster-like 3D network hierarchitectures was developed, via a template-assisted solvothermal route in diethylene glycol (DEG) solvent, followed by annealing in N2 atmosphere and subsequent corrosion of template by dilute acid. CaCO3 nanoparticles were used as the template, SnCl2 as the tin source, thiourea and l-cysteine hydrochloride monohydrate (Cys) as two different sulfur sources for a comparison study. Results show that successful fabrication of the hollow-structured SnS product mentioned above was achieved only in the case of using Cys as the sulfur source, mainly due to much stronger adhesion of Cys on CaCO3 template and microcluster-like stacking patterns of CaCO3 nanoparticles in DEG solvent. This novel 3D hierarchical SnS product owns 1–5 times higher specific surface area, unique hollow nanostructure units with rich mesopores inside the shells, and scattering-enhanced absorption in UV–vis light region, as against those previously reported micro-scale tin sulfide 3D hierarchitectures assembled by nanopetals, nanosheets, nanorods, nanobelts, etc. So it should have much more extensive and promising applications.

The molecular structure and vibrational, 1H and 13C NMR spectra of lidocaine hydrochloride monohydrate

The structure, vibrational and NMR spectra of the local anesthetic drug lidocaine hydrochloride monohydrate salt were investigated by B3LYP/6-311G∗∗ calculations. The lidocaine·HCl·H2O salt is predicted to have the gauche structure as the predominant form at ambient temperature with NCCN and CNCC torsional angles of 110° and −123° as compared to 10° and −64°, respectively in the base lidocaine. The repulsive interaction between the two N–H bonds destabilized the gauche structure of lidocaine·HCl·H2O salt. The analysis of the observed vibrational spectra is consistent with the presence of the lidocaine salt in only one gauche conformation at room temperature. The 1H and 13C NMR spectra of lidocaine·HCl·H2O were interpreted by experimental and DFT calculated chemical shifts of the lidocaine salt. The RMSD between experimental and theoretical 1H and 13C chemical shifts for lidocaine·HCl·H2O is 2.32 and 8.21ppm, respectively.

Safety and Efficacy of a Needle-free Powder Lidocaine Delivery System in Pediatric Patients Undergoing Venipuncture or Peripheral Venous Cannulation: Randomized Double-blind COMFORT-004 Trial

PurposeThe goal of this study was to determine if a lidocaine hydrochloride monohydrate powder intradermal system designed to provide cutaneous analgesia is efficacious, safe, and tolerable for pediatric subjects compared with a sham placebo system. MethodsCOMFORT-004, A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Confirm the Effectiveness and Safety of ALGRX 3268 in Pediatric Subjects, was a single-dose, parallel group study of children undergoing venipuncture or peripheral venous cannulation at the antecubital fossa or back of the hand. Included were subjects (3–18 years) in 3 age groups: 3–7, 8–12, and 13–18 years. Excluded were those with recent similar procedures or with implantable devices or skin pathologies at the anatomical site, insufficient cognitive skills, or allergies to local anesthetics or adhesives. Subjects were randomized to receive the needle-free powder lidocaine delivery system (active system, 0.5 mg of lidocaine/21 ± 1 bar of pressure [n = 269]) or sham placebo (n = 266) 1–3 minutes before venipuncture or peripheral venous cannulation. Analgesic efficacy was assessed patient self-report of venous access pain (Wong-Baker FACES Pain Rating Scale [3–18 years] and visual analog scale [VAS; 8–18 years]) and parental observational VAS. Safety assessments included adverse events (AEs) and relationship to study treatment. Skin signs and symptoms were graded numerically. Wong-Baker FACES scores, VAS, and parental VAS were analyzed by using an ANOVA model. Responder ratings and success rates were compared by using a Cochran-Mantel-Haenszel test stratified according to center, age group, and body site. FindingsThe active system group had significantly (P = 0.0022) less pain compared with the sham placebo in all age groups combined according to the modified Wong-Baker FACES scale. Secondary efficacy analyses found that the active system resulted in less pain as assessed by subjects’ VAS pain assessments aged 8–18 years (P = 0.1856), responder analysis (P = 0.054), and parents’ VAS assessments (P = 0.002). Venous procedures were successful in 95.5% and 96.2% of the active system and sham placebo groups, respectively. Treatment-emergent AEs, most commonly nausea and/or emesis, were not significant between groups. There were no serious AEs. The active system group had significantly more minor erythema and hemorrhage/petechiae. ImplicationsThe needle-free powder lidocaine delivery system was well tolerated and produced superior analgesia compared with sham placebo when administered 1–3 minutes before pediatric venipuncture or peripheral venous cannulation. Treatment-related AEs occurred primarily at the administration site and were infrequent, generally mild, and resolved without sequelae. ClinicalTrials.gov identifier: NCT00140088.

Re-analysis results using medians of the data from the JaCVAM-organized international validation study of the in vivo rat alkaline comet assay

The data from the JaCVAM-organized international validation study of the in vivo rat alkaline comet assay were reported and analyzed statistically using the simple means of % tail DNA. However, OECD test guideline TG 489 recommends use of the median for data analysis due to the hierarchical nature of the data. Comparison between the simple mean approach and the median based approach for positive/negative/equivocal chemical calls was conducted using the % tail DNA data for the 40 chemicals tested in the JaCVAM-organized international validation study of the in vivo rat alkaline comet assay, using liver and stomach as target organs. In the liver, two genotoxic chemicals, o-anisidine and 9-aminoacridine hydrochloride monohydrate, were positive using the median based approach but negative using the simple mean approach, and two genotoxic chemicals, 2-acetylaminofluorene and busulfan were equivocal using the median based approach but negative using the simple mean approach. In contrast, cadmium chloride (genotoxic carcinogen) was equivocal in both organs using the median based approach, while positive and equivocal in liver and stomach, respectively, using the simple mean approach. Two data sets of sodium arsenite showed equivocal and negative results for liver using the median based approach, although both data sets were equivocal using the simple mean approach. Overall, there are no large differences in terms of the genotoxic call between both approaches. However, the median based approach recommended in OECD TG 489 has an advantage toward higher precision within the groups treated with a test chemical, whereas the approach might show the lower values for the effect.

Sibutramine, a serotonin–norepinephrine reuptake inhibitor, causes fibrosis in rats

Sibutramine hydrochloride monohydrate is a weight loss agent indicated for the treatment of obesity. Although it has been banned from most markets, studies are still relevant as it is often a hidden ingredient in herbal and over the counter slimming products. Sibutramine induces liver fibrosis with steatosis in female Sprague-Dawley rats fed a high-energy diet without significant weight gain. In this study, using the same animal model, the effect of Sibutramine on lung morphology was investigated using histological evaluation of the terminal bronchiole and transmission electron microscopy evaluation of the respiratory tissue. From these results Sibutramine was found to induce lung fibrosis in Sprague-Dawley rats as increased collagen synthesis, mast cell accumulation and aggregates of Bronchus Associated Lymphoid Tissue (BALT) in the terminal bronchiole as well as increased collagen deposition in the respiratory tissue was seen.

Synthesis of diethyl (aryl)(4-oxopiperidin-1-yl)methylphosphonates

The Kabachnik–Fields reaction of 4-piperidone hydrochloride monohydrate, an aromatic aldehyde and triethyl phosphite in the presence of triethylamine and magnesium perchlorate affords diethyl (aryl)(4-oxopiperidin-1-yl)methylphosphonates in moderate yields.

OPC-28326, a selective peripheral vasodilator with angiogenic activity, mitigates postinfarction cardiac remodeling.

Although OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, was developed as a selective peripheral vasodilator with α2-adrenergic antagonist properties, it also reportedly exhibits angiogenic activity in an ischemic leg model. The purpose of this study was to examine the effect of OPC-28326 on the architectural dynamics and function of the infarcted left ventricle during the chronic stage of myocardial infarction. Myocardial infarction was induced in male C3H/He mice, after which the mice were randomly assigned into two groups: a control group receiving a normal diet and an OPC group whose diet contained 0.05% OPC-28326. The survival rate among the mice (n = 18 in each group) 4 wk postinfarction was significantly greater in the OPC than control group (83 vs. 44%; P < 0.05), and left ventricular remodeling and dysfunction were significantly mitigated. Histologically, infarct wall thickness was significantly greater in the OPC group, due in part to an abundance of nonmyocyte components, including blood vessels and myofibroblasts. Five days postinfarction, Ki-67-positive proliferating cells were more abundant in the granulation tissue in the OPC group, and there were fewer apoptotic cells. These effects were accompanied by activation of myocardial Akt and endothelial nitric oxide synthase. Hypoxia within the infarct issue, assessed using pimonidazole staining, was markedly attenuated in the OPC group. In summary, OPC-28326 increased the nonmyocyte population in infarct tissue by increasing proliferation and reducing apoptosis, thereby altering the tissue dynamics such that wall stress was reduced, which might have contributed to a mitigation of postinfarction cardiac remodeling and dysfunction.

Detection of bisphenol A based on conducting binder supported hydrophobic 1,10-PhenanNTf2 ionic liquid onto flat silver electrode by electrochemical approaches

The synthesis of room-temperature stable ionic liquids was obtained via metathesis reaction, which was accomplished by the reaction 1,10-Phenanthroline monohydrate hydrochloride with lithium-bis(trifluoromethane)sulfonamide in water (shortly, 1,10-PhenanNTf2). The prepared 1,10-PhenanNTf2 was characterized in details with various conventional methods. Finally, it was mixed with conducting binders and deposited on flat-silver electrode (AgE) to result in a sensor that has a fast response to bisphenol A (BPA) in the phosphate buffer phase (PBP). Features include high sensitivity, low-sample volume, reliability, reproducibility, ease of integration, long-term stability, and enhanced electrochemical responses. The calibration plot is linear (r2=0.9789) over the 0.1nM–0.1mM BPA concentration range. The sensitivity is ∼1.485μAμMcm−2, and the detection limit is 0.09±0.01nM (at a signal-to-noise-ratio, SNR of 3). We believe that the developed approach significantly opens up a simple, fast, highly sensitive, and environment-friendly path to fabricate ionic liquid based chemical sensors with broad application prospects.

Spectroscopic and theoretical studies of bis(dimethylphenyl betaine) hydrochloride monohydrate

Bis(dimethylphenyl betaine) hydrochloride monohydrate was prepared and characterized by FTIR, Raman spectroscopes, and B3LYP/6-311++G(d,p) calculations. In the optimized structure of the complex, two betaine moieties are joined by a very strong asymmetric hydrogen bond with an O⋯O distance of 2.439Å. The water molecule is H-bonded to one oxygen atom of dimethylphenyl betaine and chloride anion via O(w)⋯O(2) and O(w)⋯Cl distances of 3.099 and 3.167Å, respectively. The potential energy distributions (PED) were used for the assignments of IR and Raman frequencies in the experimental and calculated spectra of the title compound. Chloride anion interacts electrostatically with N+ atoms.

Poly(amide-imide) bearing imidazole groups/sulfonated polyimide blends for low humidity and medium temperature proton exchange membranes

A poly(amide-imide) (PAI) bearing imidazole groups on the polymer chain was synthesized via direct polycondensation of a synthesized diacid-diimide and 4,4′-(1,4-Phenylenediisopropylidene) bisaniline (PDBA). Diacide-diimide was synthesized by the condensation of an amino acid compound, (S)-(+)-Histidine hydrochloride monohydrate and 3,3′,4,4′-Benzophenone tetracarboxylic dianhydride (BTDA). On the other hand, a sulfonated polyimide (SPI) was also synthesized by the solution imidization of sulfonated, (4,4-diaminostilbene-2,2-disulfonic acid) (DSDSA) and non-sulfonated, 4,4′-(1,4-Phenylenediisopropylidene) bisaniline (PDBA) diamines in reaction with a six-membered naphthalene base dianhydride, 1,4,5,8-Naphthalenetetracarboxylic dianhydride (NTDA). A strong and flexible SPI membrane with good uniformity and proper thermal and mechanical properties was achieved. The SPI was then blended with different amounts of PAI and doped with phosphoric acid (PA), in order to investigate the blending influence of PAI in PA-doped blend membranes compared to the pure SPI membrane. It was found that a proper amount of PAI could effectively improve the water uptake, IEC and proton conductivity of the PA doped SPI/PAI membranes. Nevertheless the excess PAI negatively affected the membrane properties. The pure SPI with an IEC of 1.76 meq.g−1 showed a proton conductivity of 29.4 mS cm−1 at 120 °C, while PA doped SPI/PAI-10 % (w/w) as the most optimal PAI containing sample, with an IEC of 2.23, showed a proton conductivity of 69.7 mS cm−1 at 140 °C. The proton conductivity measurements were performed at 40 % relative humidity.

In vivo comet assay of acrylonitrile, 9-aminoacridine hydrochloride monohydrate and ethanol in rats

As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay, we examined the ability of acrylonitrile, 9-aminoacridine hydrochloride monohydrate (9-AA), and ethanol to induce DNA damage in the liver and glandular stomach of male rats. Acrylonitrile is a genotoxic carcinogen, 9-AA is a genotoxic non-carcinogen, and ethanol is a non-genotoxic carcinogen. Positive results were obtained in the liver cells of male rats treated with known genotoxic compounds, acrylonitrile and 9-AA.

ChemInform Abstract: Molecular Perspectives on Solid‐State Phase Transformation and Chemical Reactivity of Drugs: Metoclopramide as an Example

AbstractReview: 117 refs.

Vibrational and thermal analyses of multicomponent crystal forms of the anti-HIV drugs lamivudine and zalcitabine

The vibrational and thermal characterizations of four multicomponent molecular crystals of lamivudine, namely, lamivudine hydrochloride anhydrate (1), lamivudine hydrochloride monohydrate (2), lamivudine duplex I (3), with a 8:2:2:1:4 lamivudine:maleic acid:HCl:(CH3)2CHOH:H2O stoichiometry, being all three more soluble in water than the commercial solid form of lamivudine, and lamivudine maleate (4), have been performed here by infrared (IR) and Raman spectroscopy, differential scanning calorimetry (DSC), and thermogravimetry (TG). Furthermore, the vibrational spectra of zalcitabine hydrochloride (5), isostructural to 1 but with a methylene moiety in the 3′-position of the five-membered ring instead of sulfur in lamivudine, have also been measured in order to point out the role of this molecular substitution and conformation in the vibrational modes of the salts. In fact, scattering bands at the high frequency range relative to CH stretching modes are not superimposable in the Raman spectra of 1 and 5, even though these crystal forms are assembled with the same molecular conformation and intermolecular packing. At the same time, the structural similarity between 1 and 5 can be reflected in their IR spectra, as in the carbonyl and iminium stretching bands shifted to lower frequencies as consequence of their hydrogen bonding engagement. Furthermore, a scattering band at 3057cm−1 is observed only in the Raman spectra of crystal forms present with their 5′-CH2OH moiety in–gauche conformation, namely, 2–4. It is absent in the Raman spectra of 1 and 5 whose 5′-CH2OH moiety adopts +gauche conformation. In–gauche conformation, the 5′-OH oxygen is pointed toward one of the two aromatic CH hydrogens. Consequently, there is formation of an intramolecular hydrogen bond between them, shifting the aromatic CH stretching band to a lower frequency. The DFT calculations have also revealed in-phase and out-of-phase couplings of the two aromatic CH stretchings in the Raman spectra of 1, which is without intramolecular hydrogen bond due to +gauche conformation of 5′-CH2OH moiety. Both coupled vibrational modes are observed in the corresponding experimental spectrum as a single peak because of their similar frequencies. On contrary, aromatic CH stretching modes are not coupled in 2 due to the intramolecular hydrogen bond, resulting in resolution of the Raman bands. Thermal events in DSC and TG curves of 1 and 2 are also in agreement with crystal stoichiometry as observed from single-crystal X-ray diffraction analysis.

English

Grapefruit (Citrus Paradise, family Rutaceae) is a citrus fruit that is low in calories and rich in dietary fibers. Sibutramine (Sibutramine hydrochloride monohydrate) is an anti-obesity drug that enhances satiety. The effect of grapefruit juice and sibutramine on body weight and neurotransmitters controlling appetite was investigated in obese rats. &nbsp;Rats were assigned to two dietary groups for 3 weeks; control group (n=6) was fed commercial standard pellets diet and obese group (n=24) was fed cafeteria diet (hypercaloric diet consisting of highly palatable food). The effect of sibutramine and grapefruit juice was studied on obese rats. Statistical difference and interactions were evaluated through one-way analysis of variance test (one-way ANOVA) followed by Dunnett&rsquo;s test was used for means of different groups. For all statistical tests done, a 0.05 level of probability was used as the criterion for significance. Grapefruit juice produced its weight reduction effect after 1 week of administration and lasted till the end of the experiment and did not affect brain neurotransmitters. Sibutramine produced its weight reduction effect after 1 week of administration and lasted for only 2 weeks and produced an increase in brain noradrenaline while grapefruit juice produced its effect from the first week till the end of the study. It can be concluded that grapefruit juice is better than sibutramine since its effect lasted till the end of the experiment and also did not affect brain noradrenaline. &nbsp;Key words: Obesity, sibutramine, grapefruit juice, cafeteria diet.

Development and validation of sensitive kinetic spectrophotometric method for the determination of moxifloxacin antibiotic in pure and commercial tablets

New, accurate, sensitive and reliable kinetic spectrophotometric method for the assay of moxifloxacin hydrochloride (MOXF) in pure form and pharmaceutical formulations has been developed. The method involves the oxidative coupling reaction of MOXF with 3-methyl-2-benzothiazolinone hydrazone hydrochloride monohydrate (MBTH) in the presence of Ce(IV) in an acidic medium to form colored product with lambda max at 623 and 660nm. The reaction is followed spectrophotometrically by measuring the increase in absorbance at 623nm as a function of time. The initial rate and fixed time methods were adopted for constructing the calibration curves. The linearity range was found to be 1.89–40.0μgmL−1 for initial rate and fixed time methods. The limit of detection for initial rate and fixed time methods is 0.644 and 0.043μgmL−1, respectively. Molar absorptivity for the method was found to be 0.89×104Lmol−1cm−1. Statistical treatment of the experimental results indicates that the methods are precise and accurate. The proposed method has been applied successfully for the estimation of moxifloxacin hydrochloride in tablet dosage form with no interference from the excipients. The results are compared with the official method.