Theophylline–gentisic acid (1/1)

In the title 1:1 cocrystal, C7H8N4O2·C7H6O4, the anti-asthmatic drug theophylline (systematic name: 1,3-dimethyl-7H-purine-2,6-dione) and a non-steroidal anti-inflammatory drug, gentisic acid (systematic name: 2,5-dihydroxy­benzoic acid) crystallize together, forming two-dimensional hydrogen-bonded sheets involving N—H⋯O and O—H⋯N hydrogen bonds. The overall crystal packing features π–π stacking inter­actions [centroid–centroid distance = 3.348 (1) Å]. The cocrystal described herein belongs to the class of pharmaceutical cocrystals involving two active pharmaceutical ingredients which has been relatively unexplored to date

N,N-Dimethylpyridin-4-aminium 1-phenyl­cyclo­pentane-1-carboxyl­ate monohydrate

The cation of the title salt, C7H11N2 +·C12H13O2 −·H2O, is planar (r.m.s. deviation = 0.0184 Å). In the crystal, the cation, anion and water mol­ecule are linked by O—H⋯O and N—H⋯O hydrogen bonds, forming a chain running along the a axis

Nitro­furan­toin methanol monosolvate

The anti­biotic nitro­furan­toin {systematic name: (E)-1-[(5-nitro-2-fur­yl)methyl­idene­amino]­imidazolidine-2,4-dione} crys­tallizes as a methanol monosolvate, C8H6N4O5·CH4O. The nitro­furan­toin mol­ecule adopts a nearly planar conformation (r.m.s. deviation = 0.0344 Å). Hydrogen bonds involve the co-operative N—H⋯O—H⋯O heterosynthons between the cyclic imide of nitro­furan­toin and methanol O—H groups. There are also C—H⋯O hydrogen bonds involving the nitro­furan­toin mol­ecules which support the key hydrogen-bonding synthon. The overall crystal packing is further assisted by weak C—H⋯O inter­actions, giving a herringbone pattern

Thermal and in situ x-ray diffraction analysis of a dimorphic co-crystal 1:1 caffeine-glutaric acid

YesSpurred by the enormous interest in co-crystals from the pharmaceutical industry, many novel co-crystals of active pharmaceutical ingredients have been discovered in recent years and this has in turn led to an increasing number of reports on polymorphs of co-crystals. Hence, a thorough characterization and understanding of co-crystal polymorphs is a valuable step during drug development. The purpose of this study is to perform in situ structural analysis and to determine thermodynamic stability of a dimorphic co-crystal system, 1:1 caffeine-glutaric acid (CA-GA, Forms I and II). We performed thermal and structural characterizations by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot-stage microscopy (HSM), slurry and in situ variable temperature X-ray diffraction (VTXRD). For completeness, we have also re-determined crystal structures of CA-GA Forms I and II at 180 K using single crystal X-ray diffraction. Our results revealed that Form II is stable and Form I is metastable at ambient conditions. Further, the results suggest that the dimorphs are enantiotropically related and the transition temperature is estimated to be 79 Celcius degrees.This work was supported by Science and Engineering Research Council of A*STAR (Agency for Science, Technology and Research), Singapore

2-Amino­pyridinium 1-phenyl­cyclo­propane-1-carboxyl­ate

In the title salt, C5H7N2 +·C10H9O2 −, 2-amino­pyridine and 1-phenyl­cyclo­propane-1-carb­oxy­lic acid crystallize together, forming a 2-amino­pyridinium–carboxyl­ate supra­molecular heterosynthon involving two N—H⋯O hydrogen bonds, which in turn dimerizes to form a four-component supra­molecular unit also sustained by N—H⋯O hydrogen bonding. A C—H⋯π inter­action between a pyridine C—H group and the centroid of the phenyl ring of the anion further stabilizes the four-component supra­molecular unit. The overall crystal packing also features C—H⋯O inter­actions

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Impact assessment of waste management options in Singapore

ABSTRACT This paper describes the application of life cycle assessment for evaluating various waste management options in Singapore, a small-island city state. The impact assessment method by SimaPro is carried out for comparing the potential environmental impacts of waste treatment options including landfilling, incineration, recycling, and composting. The inventory data include gases and leachate from landfills, air emissions and energy recovery from incinerators, energy (and emission) savings from recycling, composting gases, and transport pollution. The impact assessment results for climate change, acidification, and ecotoxicity show that the incineration of materials imposes considerable harm to both human health and the environment, especially for the burning of plastics, paper/cardboard, and ferrous metals. The results also show that, although some amount of energy can be derived from the incineration of wastes, these benefits are outweighed by the air pollution (heavy metals and dioxins/furans) that incinerators produce. For Singapore, landfill gases and leachate generate minimal environmental damage because of the nation's policy to landfill only 10% of the total disposed wastes. Land transportation and separation of waste materials also pose minimal environmental damage. However, sea transportation to the landfill could contribute significantly to acidification because of the emissions of sulfur oxides and nitrogen oxides from barges. The composting of horticultural wastes hardly imposes any environmental damage. Out of all the waste strategies, the recycling of wastes offers the best solution for environmental protection and improved human health for the nation. Significant emission savings can be realized through recycling

Understanding the salt-dependent outcome of glycine polymorphic nucleation

10.3390/pharmaceutics13020262Pharmaceutics132Jan-1

Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: I. Effect of formulation variables on the physicochemical properties, drug release and stability of clotrimazole-loaded nanoparticles

10.1088/0957-4484/25/10/105101Nanotechnology2510-NNOT

Growth Behaviors of Two Similar Crystals: The Great Difference

The growth of two structurally similar polar crystals, γ-glycine and dl-alanine, in their aqueous supersaturated solutions in the presence of typical inorganic salts was studied using <i>in situ</i> microscopic observations. Surprisingly, it was found that their growth behaviors largely differ. The most unexpected finding was that the face growth at each of γ-glycine polar <i>c</i> ends is inhibited, while the face growth at each of dl-alanine c ends is accelerated by all the common inorganic salts studied, despite the fact that the structures of the associated faces are strikingly akin. These unusual observations were explained at the molecular level. In particular, the role of the hydrophobic methyl groups exposed at the crystal faces was highlighted, demonstrating an interesting case in which a small variation in crystal face hydrophilicity can lead to a marked difference in face growth behaviors