Nicotine has been shown to affect attentional and mnemonic processes. However, whether these effects are due to changes in perceptual and/or motor aspects of the tasks is not at all clear. This study tested the hypothesis that nicotine from cigarette smoking has differential effects on perceptual and motor processes, as reflected by event-related potentials (ERPs) and reaction times (RTs), respectively, and that perceptual effects may be specific to changes in working memory. ERPs. RTs and performance accuracy were recorded from smokers and nonsmokers during a serial-probe recognition memory task in which lists of words or "memory sets" were followed by a probe word that was either in-set or out-of-set. Smokers were tested in a "smoking" and a 12-h "deprived" condition. Smoking-smokers and deprived-smokers exhibited fast RTs to in-set and out-of-set probes relative to a group of nonsmokers. They exhibited even faster RTs when the inset probe word matched the first or last item in the memory set. Thus, smokers as a group showed enhanced primacy and recency effects suggesting that smoking specifically facilitates processes related to the motor output aspects of working memory. Different effects characterized the electrophysiology. Larger P300s were recorded to in-set compared to out-of-set probes by both subject groups. Smoking smokers exhibited enhanced P300s to both types of probes. When smokers abstained for 12 h (deprived smokers), the differences in P300 amplitude were reduced but not eliminated. Smoking smokers exhibited faster P300 latencies to in-set probes, while deprived smokers showed delayed latencies relative to nonsmokers. Primacy and recency P300 effects characterized nonsmokers and deprived smokers. However, this relationship was reversed in the Smoking condition. These results support the hypotheses that nicotine has distinct effects on memory-related perceptual and motor aspects of working memory. The increase in efficiency of the memory search with nicotine is consistent with the functional role of the cholinergic system in maintaining a state "appropriate for efficient information processing."
Clarithromycin (CAM) is known to be poorly water-soluble and acid-labile drug. Various alkalizers such as MgO, Na2CO3, Na2HPO4 and NaHCO3 were utilized to modulate the microenvironmental pH (pHM) and to improve the low stability and solubility of CAM in a crystalline-solid dispersion system (CSD). Polyvinylpyrrolidone (PVP K-30) and hydroxypropylmethylcellulose (HPMC) 4000-based CSDs containing alkalizers were prepared by cosolvent precipitation followed by evaporation process. The dried-CSDs mixed with microcrystalline cellulose, 2% croscarmellose sodium, and 1% magnesium stearate was then directly compressed into tablet. A dissolution test was carried out in 900 mL of pH 5.0 buffer solutions at 37 °C with a 50 rpm paddle speed. pHM, surface morphology, and structural behaviors were investigated. The dissolution rates of CAM in CSD containing alkalizers were improved. The drug in CSD remained crystalline as observed by differential scanning calorimetry and powder X-ray diffraction. Scanning electron microscopy revealed nearly identical images regardless of the sorts and amounts of carriers. PVP-based CSD tablet without alkalizer showed greater drug release, while HPMC-based CSD tablet without alkalizer retarded drug release due to its greater swelling capability. However, when the alkalizers were added in CSD tablet, the drug release was sharply increased. NaHCO3 induced the most rapid drug release while MgO retarded drug dissolution. Alkalizers in CSD also could maintain the pHM of the tablet above pH 5 under acidic conditions. The use of pH modifiers in CSDs could provide a useful method to improve the dissolution rate and stability of CAM via modulation of pHM without changing drug crystallinity.
The objective of this study was to design and evaluate an orodispersible film (ODF) composed of aripiprazole (ARP), prepared using a conventional solvent casting technique, and to fuse a three-dimensional (3D) printing technique with a hot-melt extrusion (HME) filament. Klucel® LF (hydroxypropyl cellulose, HPC) and PE-05JPS® (polyvinyl alcohol, PVA) were used as backbone polymers for 3D printing and solvent casting. HPC-, PVA-, and ARP-loaded filaments were applied for 3D printing using HME. The physicochemical and mechanical properties of the 3D printing filaments and films were optimized based on the composition of the polymers and the processing parameters. The crystalline states of drug and drug-loaded formulations were investigated using differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). The dissolution and disintegration of the 3D-printed films were faster than those of solvent-cast films. HPC-3D printed film was fully disintegrated within 45 ± 3.5 s. The dissolution rate of HPC films reached 80% within 30 min at pH 1.2 and pH 4.0 USP buffer. There was a difference in the dissolution rate of about 5 to 10% compared to PVA films at the same sampling time. The root mean square of the roughness (Rq) values of each sample were evaluated using atomic force microscopy. The higher the Rq value, the rougher the surface, and the larger the surface area, the more salivary fluid penetrated the film, resulting in faster drug release and disintegration. Specifically, The HPC 3D-printed film showed the highest Rq value (102.868 nm) and average surface roughness (85.007 nm). The puncture strength of 3D-printed films had desirable strength with HPC (0.65 ± 0.27 N/mm2) and PVA (0.93 ± 0.15 N/mm2) to prevent deformation compared to those of marketed film products (over 0.34 N/mm2). In conclusion, combining polymer selection and 3D printing technology could innovatively design ODFs composed of ARP to solve the unmet medical needs of psychiatric patients.
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