Torsemide Crystalline Salts with a Significant Spring-Parachute Effect.

Torsemide is a long acting pyridine sulfonylurea diuretic. Torsemide hydrochloride is widely used now, there are only a few organic acid salts reported. Cocrystallization with organic acids is an effective way to improve its solubility. Here, we reported maleate and phthalate of torsemide, in which the organic acid lost a proton transferring to the pyridine of torsemide, and torsemide interacted with organic acid through N+ - H⋯O- hydrogen bond to form salts crystal. Surprisingly, maleate showed a clear "spring" pattern in apparent solubility, whereas phthalate had a "spring-parachute" effect. Both crystalline salts kept a higher solubility than torsemide without falling. The "spring-parachute" effect of crystalline salts promoted rapid dissolution of torsemide and kept a high concentration, thereby increasing its bioavailability.

Enantiospecific crystallisation behaviour of malic acid in mechanochemical reactions with vinpocetine.

We report an intriguing example of enantioselectivity in the formation of new multicomponent crystalline solid containing vinpocetine and malic acid. Several experimental data sets confirmed that the multicomponent system presents a clear enantiospecific crystallisation behaviour both in the solid-state and in solution: only the system consisting of vinpocetine and L-malic acid produces a free-flowing solid consisting of a new crystalline form, while the experiments with D-malic acid produced an amorphous and often deliquescent material. The new vinpocetine-L-malic system crystallizes in the monoclinic space group of P21 and in a 1:1 molar ratio, where the two molecules are linked through intermolecular hydrogen bonds in the asymmetric unit. The vinpocetine-DL-malic system was partially crystalline (with also traces of unreacted vinpocetine) with diffraction peaks corresponding to those of vinpocetine-L-malic acid. Solid-state NMR experiments revealed strong ionic interactions in all the three systems. However, while vinpocetine-L-malic acid system was a pure and crystalline phase, the other two systems persistently showed the presence of unreacted vinpocetine. This resulted in a significant worsening of the dissolution profile with respect to the pure vinpocetine-L-malic crystalline salt, whose dissolution kinetics appeared superior.

Flower-inspired bionic sodium alginate hydrogel evaporator enhancing solar desalination performance.

Improving the desalination performance of the solar evaporator is the core of promoting the application of sustainable solar desalination technology. In this study, a flower-inspired bionic evaporator was successfully prepared, the bundled of black hollow sodium alginate hydrogel tubes were fixed vertically to form a flower structure with branched hydrogel tubes at the top. The prepared black flower hydrogel evaporator showed the excellent evaporation rate of 3.2 kg m-2 h-1, and the salt crystallization phenomenon during solar desalination was effectively suppressed. Three-dimensional flower configuration of the hydrogel tube with the appropriate length could increase the effective evaporation area and accelerate the evaporation process. Moreover, the hollow hydrogel network structure exhibited the stable water supply capacity to promote salt ions exchange at the evaporation interface, thereby inhibiting salt crystallization phenomenon. This study proved that constructing a 3D-shaped evaporator is an effective way to subversively improve the solar desalination performance for application.

Preparation of a crystalline salt of indomethacin and tromethamine by hot melt extrusion technology.

Although salt formation is the most ubiquitous and effective method of increasing the solubility and dissolution rates of acidic and basic drugs, it consumes large quantities of organic solvents and is a batch process. Herein, we show that the dissolution rate of indomethacin (a poorly water-soluble drug) can be increased by using hot melt extrusion of a 1:1 (mol/mol) indomethacin:tromethamine mixture to form a highly crystalline salt, the physicochemical properties of which are investigated in detail. Specifically, pH-solubility studies demonstrated that this salt exhibited a maximal solubility of 19.34 mg/mL (>1000 times that of pure indomethacin) at pH 8.19. A solvent evaporation technique was also used for salt formation. Spectroscopic analyses (infrared, nuclear magnetic resonance) of both; demonstrated, in situ salt formation with proton transfer. Powder X-ray diffraction and differential scanning calorimetry confirmed the crystalline nature of salts formed by both methods. Even though a number of amorphous salts of acidic drugs have been reported, the formation of a crystalline salt of an acidic drug by hot melt extrusion is completely unprecedented, which makes this study an important benchmark for the pharmaceutical production industry.

Performance comparison between crystalline and co-amorphous salts of indomethacin-lysine.

The introduction of a highly water soluble amino acid as co-amorphous co-former has previously been shown to significantly improve the dissolution rate of poorly water soluble drugs. In this work, dry ball milling (DBM) and liquid assisted grinding (LAG) were used to prepare different physical forms of salts of indomethacin (IND) with the amino acid lysine (LYS), allowing the direct comparison of their solid-state properties to their in vitro performance. X-ray powder diffraction and Fourier-transformed infrared spectroscopy showed that DBM experiments led to the formation of a fully co-amorphous salt, while LAG resulted in a crystalline salt. Differential scanning calorimetry showed that the samples prepared by DBM had a single glass transition temperature (Tg) of approx. 100°C for the co-amorphous salt, while a new melting point (223°C) was obtained for the crystalline salt prepared by LAG. Intrinsic dissolution and powder dissolution studies demonstrated an increased dissolution rate of the drug in the co-amorphous salt compared to pure amorphous IND and also the crystalline drug-LYS salt. Furthermore, the co-amorphous IND-LYS salt presented long term physical stability in dry conditions at 25°C and 40°C. Overall, it has been shown that the co-amorphous form of a salt has a superior performance in comparison to a crystalline salt.

Study on Prevalence of lodine Deficiency Disorder and Salt Consumption Patterns in Jammu Region.

RESEARCH QUESTION: What is the situation of iodine deficiency disorder (IDD) and salt consumption in Jammu region? HYPOTHESIS: The prevalence of IDD has decreased markedly as a result of medical as well as socio-economic factors. OBJECTIVE: To assess the magnitude of IDD in Jammu region and also assess the salt consumption patterns in the region. DESIGN: Cross-sectional study. SETTING: Primary schools in both urban and rural areas. STUDY TOOLS: Clinical examination of study population for goiter, laboratory assessment of casual urine sample for urinary iodine estimation of I(2) content of salt samples collected from sub-samples of study population. PARTICIPANTS: School children in the age group of 6-12 years were selected for study using WHO 30-cluster methodology, urine samples were collected from 15% of selected children and salt samples from 5% of sub-sample. ETHICAL CONCERN: No ethical issues were involved. RESULTS: An overall goiter prevalence of 11.98% was observed in the region. Females had a prevalence of 16.1% and males 10.1%. The median urinary iodine excretion in the region was 96.5 mug/l (range: 29.0-190.0 mug/l). Forty-nine percent of subjects had biochemical iodine deficiency with 6.7% having moderate and 42.53% mild iodine deficiency. In Jammu region, 74.47% of households consume powdered salt with 98.17% powdered salt samples having an I(2) content of greater than 15 ppm. CONCLUSION: Iodine deficiency remains a public health problem in the region, though the region seems to be in a state of nutritional transition from iodine deficiency to iodine sufficiency.