A Prodrug Strategy to Reposition Atovaquone as a Long-Acting Injectable for Malaria Chemoprotection.

Recent malaria drug discovery approaches have been extensively focused on the development of oral, smallmolecule inhibitors for disease treatment whereas parenteral routes of administration have been avoided due to limitations in deploying a shelf-stable injectable even though it could be dosed less frequently. However, an updated target candidate profile from Medicines for Malaria Venture (MMV) and stakeholders have advocated for long-acting injectable chemopreventive agents as an important interventive tool to improve malaria prevention. Here, we present strategies for the development of a long-acting, intramuscular, injectable atovaquone prophylactic therapy.

Quantification of the zymogenicity and the substrate-induced activity enhancement of complement factor D.

Complement factor D (FD) is a serine protease present predominantly in the active form in circulation. It is synthesized as a zymogen (pro-FD), but it is continuously converted to FD by circulating active MASP-3. FD is a unique, self-inhibited protease.

Genetic deletion of dopamine D1 receptors increases the sensitivity to cannabinoid CB1 receptor antagonist-precipitated withdrawal when compared with wild-type littermates: studies in female mice repeatedly exposed to the Spice cannabinoid HU-210.

Rationale: The emergence of the consumption of highly potent synthetic cannabinoid receptor agonists (spice drugs) that produce important neurological symptoms has prompted the research on the consequences of acute and chronic use of these new psychoactive substances. Most studies on cannabinoid dependence have been performed in male animals, and there is a need of studies using female subjects.

Objectives: In the present study, we evaluated only in female animals the role of dopamine D1 receptors in the behavioral responses induced by acute and repeated stimulation of cannabinoid CB1 receptors, including the development of physical dependence, since cannabinoid CB1 receptors are co-localized with dopamine D1 receptors on GABAergic neurons projecting to the substantia nigra.

Abrupt cessation of reboxetine along alcohol deprivation results in alcohol intake escalation after reinstatement of drinking.

Major depression (MD) is a frequent comorbidity in alcohol use disorder (AUD) patients. Antidepressant prescription is often limited by poor clinical outcomes or unwanted side effects in comorbid AUD-MD patients. Recent studies suggest that abrupt cessation of selective serotonin reuptake inhibitors antidepressant treatment increases alcohol consumption after an alcohol deprivation period in rats.

Rapid quantitative analysis of magnesium stearate in tablets using laser-induced breakdown spectroscopy.

Purpose: Laser-induced breakdown spectroscopy (LIBS) was evaluated for its potential as a process analytical tool for the rapid determination of magnesium stearate (MgSt) distribution within and between tablets as well as between batches in a typical manufacturing run, and for the comparison of direct-compression and roller-compaction processes.

Methods: These studies were conducted using a prototype instrument and a commercial PharmaLIBS unit, both based on pulsed Nd:YAG laser radiation at 1064 nm. The intensity of a magnesium spectral line either at 517.

Rapid analysis of liquid formulations containing sodium chloride using laser-induced breakdown spectroscopy.

The purpose of this work was to demonstrate the possibilities offered by laser-induced breakdown spectroscopy (LIBS) for the direct and rapid analysis of pharmaceutical liquid formulations. Sodium chloride in solution was chosen as a model compound. A pulsed Nd:YAG laser (1064 nm) was used to produce a gaseous plasma from the liquid sample.

Safety of chewable tablets for children.

New emphasis on pediatric drug development makes the availability of safe, easy-to-use dosage formulations imperative for clinical practice. Chewable tablets are a widely used pediatric dosage form; however, a literature review on the safety of this formulation has not been published. We have, therefore, determined the safety of chewable tablets in the pediatric age group based on the published literature.

A comparison of the availability of tobramycin for inhalation from vented vs unvented nebulizers.

Study Objective: To compare drug output from a vented nebulizer (Pari LC Jet Plus) with a traditional unvented nebulizer (Hudson 1730 T Up-Draft 11) using aerosolized tobramycin, which is frequently used in the treatment of cystic fibrosis.

Design: Six nebulizers of each type were filled with a 4 mL tobramycin (80 mg) solution and were driven by a compressor (Pulmo-Aide). Various inspiratory flows (VI) (0, 5, 10, 15, 20 L/min for the Pari LC Jet Plus and 0, 5, and 10 L/min for the Hudson 1730, all at 40% relative humidity) were directed through each nebulizer.

The choice of jet nebulizer, nebulizing flow, and addition of albuterol affects the output of tobramycin aerosols.

The use of inhaled antibiotics in the treatment of cystic fibrosis has become widespread despite controversy in the literature as to the appropriate dosing regimen and its effectiveness. This study compared two tobramycin (T) preparations (one with and one without the addition of albuterol) using two different jet nebulizers in order to determine if drug output would be affected. Using calibrated flows from a dry compressed gas source of 6 and 8 L/min as well as a specific compressor (Pulmo-Aide), the Hudson 1720 nebulizer was compared with the newer disposable Hudson 1730.

A comparison of pulmonary availability between Ventolin (albuterol) nebules and Ventolin (albuterol) Respirator Solution.

The two most common albuterol preparations used for nebulization are: (1) Ventolin (albuterol) respirator solution (Glaxo Canada Inc; Montreal, Canada) of which 2.5 mg (0.5 mL) is diluted with 2 mL of normal saline solution, and (2) the preservative-free, prediluted Ventolin (albuterol) Nebules PF (Glaxo) (2.

Aerosolized L-693,989 for Pneumocystis carinii prophylaxis in rats.

Water-soluble pneumocandin L-693,989, a potent antipneumocystis agent in the rat model for Pneumocystis carinii pneumonia (PCP), inhibits P. carinii cyst development and effectively prevents the development of PCP when used as a prophylactic agent (D. M.

Physiological disposition of aerosolized MK-679 in rats.

[14C]MK-679, a potent antagonist of leukotriene D4, was suspended in freon under pressure and sprayed into rat lungs through a tracheal cannula. The particle size of the drug was 1 to 5 microns, and the mean dose was 98.8 +/- 4.

Solid-state phase transitions initiated by water vapor sorption of crystalline L-660,711, a leukotriene D4 receptor antagonist.

Significant water vapor sorption at room temperature by the crystalline and lyophilized forms of L-660,711, a potent, selective leukotriene D4 receptor antagonist, has been measured and shown to produce increasingly more nonflowing, semisolid masses with increasing relative humidity. Thermal analysis, SEM, powder X-ray diffraction, solid-state NMR, and thermomicroscopic measurements reveal that water vapor sorbed at room temperature converts the crystalline form to a noncrystalline form resembling the lyophilized sample. Evidence is presented to indicate that L-660,711 has surface active properties with a critical micellization concentration of approximately 1 x 10(-4) M and an ability to form thermotropic and lyotropic mesomorphic phases when the crystal is heated above 80 degrees C in the anhydrous state; it is lyophilized from aqueous solution, and it is exposed to relative humidities at and above 12%, at room temperature.

Effect of compressional force on tablets containing cellulosic disintegrators I: Dimensionless disintegration values.

Spray-dried lactose tablets containing cellulosic disintegrators or microcrystalline cellulose were compressed at different compressional forces. USP disintegration times were measured as a function of pH and compressional force. Two dimensionless quantities were derived from the experimentally determined disintegration times, and their utility in the study of tablet formulations was demonstrated.

Phosphorescence studies of the interaction of myelin basic protein with phosphatidylserine vesicles.

Phosphorescence from the lone tryptophan residue has been studied to monitor the interaction of myelin basic protein with phosphatidylserine vesicles. Spectral shifts in the phosphorescence of the protein in a glycerol-buffer (70:30 w/w) solvent at low temperature are consistent with fluorescence data obtained under ambient conditions, indicating that the tryptophan side chain is exposed to the solvent in the free protein but is buried on interaction with a lipid bilayer. Measurements of the phosphorescence intensity and lifetime as a function of temperature reveal a marked protection of the tryptophan to thermally induced quenching in the presence of phosphatidylserine vesicles.

Phase diagrams for impure lipid systems. Application to lipid/anaesthetic mixtures.

A physical model is presented to describe theoretically the temperature-dependent interactions of lipid bilayers with small molecules such as anaesthetics. Based on an earlier model, a triangular lattice in which each site is occupied by a single lipid chain is constructed and the small (anaesthetic) molecules are assumed to occupy interstitial sites in the centre of each lattice triangle. The phase characteristics of such lipid/anaesthetic mixtures are described in terms of the interaction parameters between lipid-lipid, lipid-anaesthetic and anaesthetic-anaesthetic molecules.

Alteration of the erythrocyte ultrastructure and blood viscosity by morphine.

The effects of acute morphine administration on intact erythrocytes and on their flow properties were studied by measuring the mean cell volume, cell geometry, and whole blood and plasma viscosities. Morphine caused a small (2-7%) increase in mean cell volume. Changes in cell geometry were found to be time dependent and most pronounced in concave portions of the red cells.