Liquid-filled hard gelatin capsules : excipient/capsule compatibility studies

Encapsulation of pharmaceutical formulations as liquids or semisolids, within hard gelatin capsules, presents an important oral dosage strategy for poorly water-soluble drugs, resulting in good bioavailability and reproducible drug absorption. In addition, this technology offers an inherently safer process than powder filled capsules and tablets for highly potent or cytotoxic drugs by avoiding dust generation. Here we present a compatibility study of hard gelatin capsules with common excipients in absence of active pharmaceutical

An Overview of the Methylxanthines and their Regulation in the Horse

Caffiene, theophylline and theobromine are naturally occurring members of the methylxanthine family;pentoxfylline, dyphylline and enprofylline are structurally related synthetic pharmaceuticals. Caffiene has predominantly central nervous system effects, theophylline, dyphylline and enprofylline have predominantly bronchodilator effects, while theobromine is associated with diuretic responses. Pentoxfylline is thought to increase red cell deformability and facillitate blood flow through capillary beds. The methylxanthines are not highly potent agents; they are typically administered in gram doses and they tend to have relatively long half-lives. They remain detectable in plasma and urine for relatively long periods. Similarly, traces of the naturally occurring members of this family are not uncommonly identified in forensic samples. In this review we report on the detection, actions, uses and regulatory control of this group of agents in performance horses

Surface Dynamics of Crude and Weathered Oil in the Presence of Dispersants: Laboratory Experiment and Numerical Simulation

Marine oil spills can have dire consequences for the environment. Research on their dynamics is important for the well-being of coastal communities and their economies. Propagation of oil spills is a very complex physical-chemical process. As seen during the Deepwater Horizon event in the Gulf of Mexico during 2010, one of the critical problems remaining for prediction of oil transport and dispersion in the marine environment is the small-scale structure and dynamics of surface oil spills. The laboratory experiments conducted in this work were focused on understanding the differences between the dynamics of crude and weathered oil spills and the effect of dispersants. After deposition on the still water surface, a drop of crude oil quickly spread into a thin slick; while at the same time, a drop of machine (proxy for weathered) oil did not show significant evolution. Subsequent application of dispersant to the crude oil slick resulted in a quick contraction or fragmentation of the slick into narrow wedges and tiny drops. Notably, the slick of machine oil did not show significant change in size or topology after spraying dispersant. An advanced multi-phase, volume of fluid computational fluid dynamics model, incorporating capillary forces, was able to explain some of the features observed in the laboratory experiment. As a result of the laboratory and modeling experiments, the new interpretation of the effect of dispersant on the oil dispersion process including capillary effects has been proposed, which is expected to lead to improved oil spill models and response strategies

Frequency distribution of post race urine pH from Standardbreds compared with Thoroughbreds: research and regulatory significance

The concentration of drugs and drug metabolites in urine samples of racing horses is strongly influenced by urine pH(Tobin, 1981), depending on whether the drugs are weak acids or weak bases. Drugs that are weak acids tend to concentrate in besic urine. In contrast, drugs that are weak bases tend to concentrate in acidic urine. These relationships have a well-established theoretical basis (the Henderson-Hasselbalch relationship) and have been demonstrated repeatedly in experimental animals and man (Tobin, 1981). More recently, evidence suggests that these relationships also occur with clinically and forensically significant agents in equine urine (Wood, et al. 1990; Gerken et al.1991.

Stress corrosion in titanium alloys and other metallic materials

Multiple physical and chemical techniques including mass spectroscopy, atomic absorption spectroscopy, gas chromatography, electron microscopy, optical microscopy, electronic spectroscopy for chemical analysis (ESCA), infrared spectroscopy, nuclear magnetic resonance (NMR), X-ray analysis, conductivity, and isotopic labeling were used in investigating the atomic interactions between organic environments and titanium and titanium oxide surfaces. Key anhydrous environments studied included alcohols, which contain hydrogen; carbon tetrachloride, which does not contain hydrogen; and mixtures of alcohols and halocarbons. Effects of dissolved salts in alcohols were also studied. This program emphasized experiments designed to delineate the conditions necessary rather than sufficient for initiation processes and for propagation processes in Ti SCC

Absence of detectable pharmacological effects after oral administration of isoxsuprine

Isoxsuprine is reported to be a peripheral vasodilator used in human and veterinary medicine to treat ischaemic vascular disease. In horses, it is generally administered orally to treat navicular disease and other lower limb problems. To deflne the scope and duration of its pharmacological responses after oral administration, 6 horses were dosed with isoxsuprine HCI (1.2 mg/kg bwt) q. 12 h for 8 days and then tested to assess the duration and extent of pharmacological actions. There was no significant difference between isoxsuprine and control treatment values for heart rate, spontaneous activity, sweat production, anal muscle tone, core and skin temperatures, and cutaneous blood flow. The lack of pharmacological effect following oral administration was in sharp contrast to the marked response following i.v. dosing reported in earlier experiments

A GC-MS Method for the Determination of Isoxsuprine in Biological Fluids of the Horse Utilizing Electron Impact Ionization

Isoxsuprine is used to treat navicular disease and other lower-limb problems in the horse. Isoxsuprine is regulated as a class 4 compound by the Association of Racing Commissioners, International (ARCI) and, thus, requires regulatory monitoring. A gas chromatography-mass spectrometry method utilizing electron impact ionization was developed and validated for the quantitation of isoxsuprine in equine plasma or equine urine. The method utilized robotic solid-phase extraction and tri-methyl silyl ether products of derivatization. Products were bis-trimethylsilyl (TMS) isoxsuprine and tris-TMS ritodrine, which released intense quantifier ions m/z 178 for isoxsuprine and m/z 236 for ritodrine that were products of C-C cleavage. To our knowledge, this procedure is faster and more sensitive than other methods in the literature. Concentrations in urine and plasma of isoxsuprine were determined from a calibrator curve that was generated along with unknowns. Ritodrine was used as an internal standard and was, therefore, present in all samples, standards, and blanks. Validation data was also collected. The limit of detection of isoxsuprine in plasma was determined to be 2 ng/mL, the limit of quantitation of isoxsuprine in plasma was determined to be \u3c 5 ng/mL. The mean coefficient of determination for the calibrator curves for plasma was 0.9925 ± 0.0052 and for calibrator curves for urine 0.9904 ± 0.0075. The recovery efficiencies at concentrations of 50, 200, and 300 ng/mL were 76%, 73%, and 76%, respectively, in plasma and 92%, 89% and 91% in urine

Pincer-like Amido Complexes of Platinum, Palladium, and Nickel

The ligands bis(8-quinolinyl)amine (BQAH, 1), (2-pyridin-2-yl-ethyl)-(8-quinolinyl)amine (2-pyridin-2-yl-ethyl-QAH, 2), o-dimethylaminophenyl(8-quinolinyl)amine (o-(NMe_2)Ph-QAH, 3), and 3,5-dimethylphenyl(8-quinolinyl)amine (3,5-Me_2Ph-QAH, 4) have been prepared in high yield from aryl halide and amine precursors by palladium-catalyzed coupling reactions. Deprotonation of 1 with ^nBuLi in toluene affords the lithium amide complex [Li][BQA] (5), whose dimeric solid-state crystal structure is presented. Lithium amide 5 was transmetalated by TlOTf to afford the thallium(I) amido complex [Tl][BQA] (6). An X-ray structural study of 6 shows it to be a 1:1 complex of the BQA ligand and Tl. Entry into the group 10 chemistry of the parent ligand 1 was effected by both protolytic and metathetical strategies. Thus, the divalent chloride complexes (BQA)PtCl (7), (BQA)PdCl (8), and (BQA)NiCl (9) were prepared and fully characterized. An X-ray structural study for each of these three complexes shows them to be well-defined, square-planar complexes in which the auxiliary BQA ligand binds in a planar, ^η3-fashion. For comparison, the reactivity of ligands 2−4 with (COD)PtCl_2 was studied. While reaction with ligand 2 afforded an ill-defined product mixture, ligands 3 and 4 reacted with (COD)PtCl_2 to generate the unusual alkyl complexes (o-(NMe_2)Ph-QA)Pt(1,2-η^2-6-σ-cycloocta-1,4-dienyl) (10) and (3,5-Me_2Ph-QA)Pt(1,2-η^2-6-σ-cycloocta-1,4-dienyl) (11), both of which have been structurally characterized