Development of Bitter-Taste Masked Instant Jelly Formulations of Diphenhydramine Hydrochloride with Easy-to-Consume Granules.

This study developed easy-to-consume bitter taste-masking granules for the preparation of instant jelly formulations. Composite granules containing diphenhydramine hydrochloride (DPH) and polymers were prepared via spray drying. The taste-masking effect on DPH was evaluated with acceptable linearity between DPH concentration and intensity of bitterness using an electronic tongue sensor. The results indicated that ι-carrageenan could provide the greatest suppression effect on the DPH bitterness among the polymers selected for preparing spray-dried particles (SDPs). The thixotropic index (TI) of ι-carrageenan was higher than that of the other polymers. In addition, two sulfate groups per two galactose molecules in one unit of ι-carrageenan improved interaction with DPH. Compared to κ-carrageenan, the electrostatic interaction with DPH may be stronger. Easy-to-consume SDPs with ι-carrageenan were used to prepare instant jelly formulations. The instant jelly formulation containing DPH with ι-carrageenan (3.0%) met the criteria for texture properties (hardness, adhesiveness, and cohesiveness) for patients with difficulty swallowing, as specified by the Consumer Affairs Agency. Furthermore, instant jelly enhanced the bitter taste suppression of DPH. Overall, using spray-dried granules with ι-carrageenan, this technique for preparing instant jelly formulations is simple and inhibits the bitter taste of drugs, contributing to the development of oral dosage forms suitable for patients of all ages.

A Powderization Process for Encapsulating with Functional Biomaterials Using Nozzleless Electrostatic Atomization.

Powderization of oils has been used as a method to enhance the stability of polyunsaturated fatty acids. Previously, we successfully powderized soybean oil via nozzleless electrostatic atomization. The process of nozzleless electrostatic atomization process was applied to the one-step process of encapsulating oil in wall materials. The encapsulation of oils in powder is dependent on the wall materials. The present study aimed to resolve the behavior of oil encapsulated in particles using a novel method of electrostatic atomization, and to investigate the effect of wall materials on the oil content in the encapsulated formulations. The size of particles surrounding oil was dependent on the type of wall materials used for encapsulation, and the oil content within the encapsulation decreased with increase in particle size. Furthermore, wall materials with higher hydrophobicity increased the oil content within the encapsulation, as more hydrophobic particles could absorb the oil more effectively. PRACTICAL APPLICATION: Nozzleless electrostatic atomization is a new method for preparing encapsulation of oil using various wall materials.

Development of porous particles using dextran as an excipient for enhanced deep lung delivery of rifampicin.

This study aimed to develop a dry powder inhaler (DPI) formulation for enhanced deep lung delivery of rifampicin using dextrans of different molecular weights. Porous particles were formed by a spray-drying method, which was designed based on the Peclet number. The morphology of particles containing both rifampicin and dextran was dependent on the dextran concentration. The D50 values of SDPs containing rifampicin and dextran 40 or 70 at ratios of less than 1:10 were below 5 µm. The specific surface area values of spray-dried particles containing rifampicin and dextran 40 or 70 of more than 1:10 were over 20 m2/g, assuming that an increase in specific surface area was indicative of an increase in the formation ratio of a porous structure. DPI formulations that contained higher amounts of dextran had higher rifampicin contents. Thus, the formulations containing a dextran: rifampicin ratio of 1:20 had approximately 100% drug encapsulation. The formation of the porous particles can be explained by the related Peclet number, which correlates with the viscosity and surface tension of the ethanol-water solution used in preparing the particles. It was noted that the existence ratio of the porous particles increased as the viscosity of the mixed solution was increased. Furthermore, an increase in the proportion of dextran resulted in higher rifampicin loading into the particles and the formation of finer particle fractions (FPF) (<7.0 µm at a rate of 28.3 L/min, <4.8 um at a rate of 60.0 L/min). The formulations containing rifampicin and both dextrans at a ratio of more than 1:10 consisted of approximately 50% FPF at a rate of 28.3 L/min and 60.0 L/min. The results indicate that dextran is suitable to obtain porous particles via spray-drying. Additionally, the existence ratio of the porous particles can be improved by increasing the viscosity of the solution used in the preparation of the particles.

DEM Modelling of Granule Rearrangement and Fracture Behaviours During a Closed-Die Compaction.

The closed-die compaction behaviour of D-mannitol granules has been simulated by the discrete element method (DEM) to investigate the granule rearrangement and fracture behaviour during compaction which affects the compactibility of the tablet. The D-mannitol granules produced in a fluidized bed were modelled as agglomerates of primary particles connected by linear spring bonds. The validity of the model granule used in the DEM simulation was demonstrated by comparing to the experimental results of a uniaxial compression test. During uniaxial compression, the numerical results of the force-displacement curve corresponded reasonably well to the experimental data. The closed-die compaction of the modelled granules was carried out to investigate the rearrangement and fracture behaviours of the granule at different upper platen velocities. The forces during closed-die compaction calculated by DEM fluctuated in the low-pressure region due to the rearrangement of granules. A Heckel analysis showed that the force fluctuation occurred at the initial bending region of the Heckel plot, which represents the granule rearrangement and fracture. Furthermore, the upper platen velocity affected the trend of compaction forces, which can lead to compaction failure due to capping. These results could contribute to designing the appropriate granules during closed-die compaction.

Inhibition of Photodegradation of Highly Dispersed Folic Acid Nanoparticles by the Antioxidant Effect of Transglycosylated Rutin.

We developed highly dispersible and photostable nanoparticles of vitamin, folic acid (FA). FA was wet bead milled with milling and dispersing adjuvants and transglycosylated compounds such as α-glucosyl hesperidin (Hesperidin-G) and rutin (Rutin-G), which solubilized FA. The milled slurries of FA particles with transglycosylated compounds consisted of nanosized particles with a median diameter of <100 nm. The lyophilized formulations of these slurries retained their nanometer size after resuspension in water with no aggregation. The apparent solubility of FA in these formulations was 100-fold higher than that of untreated FA. The solubilizing effect of Rutin-G may affect the particle size reduction and dispersibility of FA. The photostability results showed that the strong antioxidant activity of Rutin-G substantially increased the photostability of FA solution. On the basis of these results, bead milling of FA with Rutin-G is a promising technique for developing highly dispersible, photostable nanoparticle FA formulations.

Numerical evaluation of the capping tendency of microcrystalline cellulose tablets during a diametrical compression test.

Capping is one of the major problems that occur during the tabletting process in the pharmaceutical industry. This study provided an effective method for evaluating the capping tendency during diametrical compression test using the finite element method (FEM). In experiments, tablets of microcrystalline cellulose (MCC) were compacted with a single tabletting machine, and the capping tendency was determined by visual inspection of the tablet after a diametrical compression test. By comparing the effects of double-radius and single-radius concave punch shapes on the capping tendency, it was observed that the capping tendency of double-radius tablets occurred at a lower compaction force compared with single-radius tablets. Using FEM, we investigated the variation in plastic strain within tablets during the diametrical compression test and visualised it using the output variable actively yielding (AC YIELD) of ABAQUS. For both single-radius and double-radius tablets, a capping tendency is indicated if the variation in plastic strain was initiated from the centre of tablets, while capping does not occur if the variation began from the periphery of tablets. The compaction force estimated by the FEM analysis at which the capping tendency was observed was in reasonable agreement with the experimental results.

Kinetics of co-crystal formation with caffeine and citric acid via liquid-assisted grinding analyzed using the distinct element method.

The kinetics of co-crystal formation of caffeine (CF) with citric acid (CTA) was evaluated. Ball milling of CF and CTA in molar ratios of 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, and 1:4 was performed by the liquid-assisted grinding (LAG) method. The samples were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Two types of co-crystals (co-crystal-1, a 1:1 CF-CTA co-crystal; and co-crystal-2, a new co-crystal form) were obtained. The kinetic characteristics of this new co-crystal formation were assessed by calculating the ball impact energy and force using the distinct element method (DEM) simulations. The results indicated that co-crystal-2 creation occurred under a condition in which the ball impact force exceeded a certain threshold value. Moreover, the total ball impact energy was positively correlated with co-crystal formation, exhibiting a higher ball impact force than the threshold value. The kinetics of co-crystal-2 formation was almost consistent with the Jander equation. Consequently, co-crystal-2 formation could be explained according to a three-dimensional diffusion mechanism.

Absorption improvement of tranilast by forming highly soluble nano-size composite structures associated with α-glucosyl rutin via spray drying.

Tranilast (TL) composite particles with α-glucosyl rutin (Rutin-G) were developed to improve the solubility and oral bioavailability of TL. Composite formulation of TL/Rutin-G was prepared using the spray-drying method, and their physicochemical properties were evaluated with respect to the morphology, particle size distribution, solubility and crystallinity. The nanostructure formation of Rutin-G was characterized by dynamic light scattering and transmission electron microscopy when Rutin-G or TL/Rutin-G spray-dried particles (SDPs) were introduced into water. A pharmacokinetic study was also performed to assess the improvement of oral absorption in rats. TL/Rutin-G SDPs were spherical particles with a diameter of 5.5µm. Even in the acidic condition, the remarkable improvement in solubility of TL was achieved, as evidenced by a 32.2-fold increase in solubility compared with untreated TL. The median size of Rutin-G nanostructures in water was 2nm. The formation of Rutin-G nanostructures and their drug inclusion properties may enhance the solubility and dissolution behavior of TL. A drastic increase was found in the exposure of TL in rats, with an increase in Cmax and AUC values of 114- and 36.4-fold, respectively, compared with those of untreated TL. These findings indicated that a TL formulation spray-dried with Rutin-G could enhance its solubility and absorption and thus its therapeutic properties.

Optimised mounting conditions for poly (ether sulfone) in radiation detection.

Poly (ether sulfone) (PES) is a candidate for use as a scintillation material in radiation detection. Its characteristics, such as its emission spectrum and its effective refractive index (based on the emission spectrum), directly affect the propagation of light generated to external photodetectors. It is also important to examine the presence of background radiation sources in manufactured PES. Here, we optimise the optical coupling and surface treatment of the PES, and characterise its background. Optical grease was used to enhance the optical coupling between the PES and the photodetector; absorption by the grease of short-wavelength light emitted from PES was negligible. Diffuse reflection induced by surface roughening increased the light yield for PES, despite the high effective refractive index. Background radiation derived from the PES sample and its impurities was negligible above the ambient, natural level. Overall, these results serve to optimise the mounting conditions for PES in radiation detection.

Poly (ether sulfone) as a scintillation material for radiation detection.

Considerable attention has been drawn to the advantages of using aromatic ring polymers for scintillation materials in radiation detection. Thus, it is important to identify and characterise those with the best potential. Here, we characterise poly (ether sulfone) (PES), which is an amber-coloured transparent resin that possesses sulfur as a main component and has a density of 1.37 g/cm(3). PES emits short-wavelength light with a 350-nm maximum. By taking into account its emission spectrum, we demonstrate that its effective refractive index is 1.74. Light yield distributions generated by (137)Cs and (207)Bi radioactive sources were obtained. PES has a light yield that is 2.21 times that of poly (ethylene terephthalate), and 0.31 times that of poly (ethylene naphthalate). The energy response to 5,486 keV alpha particles emitted from (241)Am was 546 ± 81 keV electron equivalents (keVee), while the energy resolution was 17.0 ± 0.1%. The energy response to 6,118 keV alpha particles emitted from (252)Cf was 598 ± 83 keVee, while the energy resolution was 16.0 ± 0.1%. Overall, PES has potential for use as a scintillation material in radiation detection.

Mechanism of wavelength conversion in polystyrene doped with benzoxanthene: emergence of a complex.

Fluorescent guest molecules doped in polymers have been used to convert ultraviolet light into visible light for applications ranging from optical fibres to filters for the cultivation of plants. The wavelength conversion process involves the absorption of light at short wavelengths followed by fluorescence emission at a longer wavelength. However, a precise understanding of the light conversion remains unclear. Here we show light responses for a purified polystyrene base substrates doped with fluorescent benzoxanthene in concentrations varied over four orders of magnitude. The shape of the excitation spectrum for fluorescence emission changes significantly with the concentration of the benzoxanthene, indicating formation of a base substrate/fluorescent molecule complex. Furthermore, the wavelength conversion light yield increases in three stages depending on the nature of the complex. These findings identify a mechanism that will have many applications in wavelength conversion materials.

Optimized mounting of a polyethylene naphthalate scintillation material in a radiation detector.

Polyethylene naphthalate (PEN) has great potential as a scintillation material for radiation detection. Here the optimum mounting conditions to maximize the light collection efficiency from PEN in a radiation detector are discussed. To this end, we have determined light yields emitted from irradiated PEN for various optical couplings between the substrate and the photodetector, and for various substrate surface treatments. The results demonstrate that light extraction from PEN is more sensitive to the optical couplings due to its high refractive index. We also assessed the extent of radioactive impurities in PEN as background sources and found that the impurities are equivalent to the environmental background level.

SPICE-NIRS microbeam: a focused vertical system for proton irradiation of a single cell for radiobiological research.

The Single Particle Irradiation system to Cell (SPICE) facility at the National Institute of Radiological Sciences (NIRS) is a focused vertical microbeam system designed to irradiate the nuclei of adhesive mammalian cells with a defined number of 3.4 MeV protons. The approximately 2-µm diameter proton beam is focused with a magnetic quadrupole triplet lens and traverses the cells contained in dishes from bottom to top. All procedures for irradiation, such as cell image capturing, cell recognition and position calculation, are automated. The most distinctive characteristic of the system is its stability and high throughput; i.e. 3000 cells in a 5 mm × 5 mm area in a single dish can be routinely irradiated by the 2-µm beam within 15 min (the maximum irradiation speed is 400 cells/min). The number of protons can be set as low as one, at a precision measured by CR-39 detectors to be 99.0%. A variety of targeting modes such as fractional population targeting mode, multi-position targeting mode for nucleus irradiation and cytoplasm targeting mode are available. As an example of multi-position targeting irradiation of mammalian cells, five fluorescent spots in a cell nucleus were demonstrated using the γ-H2AX immune-staining technique. The SPICE performance modes described in this paper are in routine use. SPICE is a joint-use research facility of NIRS and its beam times are distributed for collaborative research.

Specific activity and activity ratios of radionuclides in soil collected about 20 km from the Fukushima Daiichi Nuclear Power Plant: Radionuclide release to the south and southwest.

Soil samples at different depths (0-2, 5-7 and 10-12cm) were collected from J Village, about 20km south of Fukushima Daiichi Nuclear Power Plant (FNPP) to determine their radionuclide specific activities and activity ratios. The concentrations and activity ratios of (131)I, (134, 136, 137)Cs and (129m)Te were obtained, but only trace amounts of (95)Nb, (110m)Ag and (140)La were detected which were too low to provide accurate concentrations. Radionuclides such as (95)Zr, (103, 106)Ru and (140)Ba that were found in Chernobyl fallout, were not found in these soil samples. This suggests that noble gasses and volatile radionuclides predominated in the releases from FNPP to the terrestrial environment. The average activity ratios of (131)I/(137)Cs, (134)Cs/(137)Cs, (136)Cs/(137)Cs and (129m)Te/(137)Cs were 55, 0.90, 0.22 and 4.0 (corrected to March 11, 2011) in the 0-2cm soil samples of April 20 and 28, 2011.

Diffusion behavior in a liquid-liquid interfacial crystallization by molecular dynamics simulations.

Interfacial crystallization, such as surface crystallization in solution (solid-liquid) and liquid-liquid crystallization, gives us an asymmetric reaction field and is a technique for morphology control of crystals. In the liquid-liquid crystallization, the concentration distribution of solute ions and solvent molecules at the liquid-liquid interface directly relates to nucleation, crystal growth, and crystal morphology. Nonequilibrium molecular dynamics (MD) simulations have been performed at interfaces in NaCl solution/1-butanol and KCl solution/1-butanol system in order to clarify diffusion behavior of solute ions and solvent molecules. As simulation results, the hydrated solute ions were dehydrated with the diffusion of water from solution phase into 1-butanol phase. The different dehydration behaviors between NaCl and KCl solution can be also obtained from MD simulation results. Aggregated ions or clusters were formed by the dehydration near the solution/1-butanol interface. By comparison on the normalized number of total solute ions, the size and number of generated cluster in KCl solution/1-butanol interface are larger than those in the NaCl system. This originates in the difference hydration structures in the each solute ion.

[Preliminary survey for communicating risk in medical exposure--perception of risk among nurses working in radiology].

A questionnaire survey was conducted on radiation risk and medical exposure, particularly in applications involving children. The survey was targeted at nurses (170 females) engaged in important roles in communicating risk regarding medical exposure. The questionnaire survey yielded the following findings. 1) A significant number of respondents associated the word "radiation" with "cancer treatment," "exposure," and "X-ray pictures." Perceptions about "food exposure" differed between respondents with children and those without. 2) Among the potential health problems posed by radiation, "effects on children," "cancer and leukemia," and "genetic effects" were perceived as the most worrisome. Significant differences in perception were noted regarding infertility between respondents with children and those without. 3) Concerning the effects of medical exposure on fetuses/children, only 10 percent of all respondents replied that they were not anxious about negative effects in either case. Among the respondents who felt uneasy about these aspects, most tended to assess exposed parts, doses, damage potentially suffered, timing of occurrence, and uncertainty, based on their professional experience and knowledge, to rationally distinguish acceptable risks from unacceptable ones and to limit concern to the unacceptable aspects.