Modeling of quantitative relationships between physicochemical properties of active pharmaceutical ingredients and tensile strength of tablets using a boosted tree

Objectives: The aim of this study was to explore the potential of boosted tree (BT) to develop a correlation model between active pharmaceutical ingredient (API) characteristics and a tensile strength (TS) of tablets as critical quality attributes.

Methods: First, we evaluated 81 kinds of API characteristics, such as particle size distribution, bulk density, tapped density, Hausner ratio, moisture content, elastic recovery, molecular weight, and partition coefficient. Next, we prepared tablets containing 50% API, 49% microcrystalline cellulose, and 1% magnesium stearate using direct compression at 6, 8, and 10?kN, and measured TS. Then, we applied BT to our dataset to develop a correlation model. Finally, the constructed BT model was validated using k-fold cross-validation.

Results: Results showed that the BT model achieved high-performance statistics, whereas multiple regression analysis resulted in poor estimations. Sensitivity analysis of the BT model revealed that diameter of powder particles at the 10th percentile of the cumulative percentage size distribution was the most crucial factor for TS. In addition, the influences of moisture content, partition coefficients, and modal diameter were appreciably meaningful factors.

Conclusions: This study demonstrates that BT model could provide comprehensive understanding of the latent structure underlying APIs and TS of tablets.     

Visualization of TiO2 Reduction Behavior in Molten Salt Electrolysis

Metallurgical and Materials Transactions B - An in situ observation technique of the TiO2 interfacial behavior in molten LiCl-KCl electrolysis was developed. The variation of the thin TiO2...     

Acoustic recognition of counterions in ion-exchange resins

In a coupled acoustic-gravity field, particles are aggregated at a particular position determined by their acoustic properties, such as density and compressibility. The observation of the aggregation of cation-exchange resin particles in this field has confirmed that the types of countercations strongly affect the behavior of the particles. Detailed analyses have revealed that the different behavior comes not from the density of the resins but from their compressibility as far as H+- and NBu4+-form cation-exchange resins are concerned. Since these resins are aggregated at the different positions, we can gain information of counterions from aggregation coordinates. Counterions can thus be recognized through the observation of the aggregation behavior of resin particles in the field without chemical analyses routinely employed in ion-exchange studies.     

Atmospheric outflow of anthropogenic semivolatile organic compounds from East Asia in spring 2004

To estimate the emissions of anthropogenic semivolatile organic compounds (SOCs) from East Asia and to identify unique SOC molecular markers in Asian air masses, high-volume air samples were collected on the island of Okinawa, Japan between 22 March and 2 May 2004. Contributions from different source regions (China, Japan, the Koreas, Russia, and ocean/local) were estimated by use of source region impact factors (SRIFs). Elevated concentrations of hexachlorobenzene (HCB), hexachlorcyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), and particulate-phase polycyclic aromatic hydrocarbons (PAHs) were attributed to air masses from China. A large proportion of the variation in the current-use pesticides, gas-phase PAHs, and polychlorinated biphenyl (PCB) concentrations was explained by meteorology. Chlordanes showed a technical mixture profile and similar concentrations regardless of source region. alpha/gamma HCH and trans/cis chlordane ratios did not vary significantly with different source regions and had regional averages of 2.5 +/- 1.0 and 1.2 +/- 0.3, respectively. Particulate-phase PAH concentrations were significantly correlated (p value < 0.05) with other incomplete combustion byproduct concentrations, including elemental mercury (Hg0), CO, NOx, black carbon, submicrometer aerosols, and SO2. By use of measured PAH, CO, and black carbon concentrations and estimated CO and black carbon emission inventories, the emission of six carcinogenic particulate-phase PAHs was estimated to be 1518-4179 metric tons/year for Asia and 778-1728 metric tons/year for China, respectively. These results confirm that East Asian outflow contains significant emissions of carcinogenic particulate-phase PAHs.     

A Dietary Oxysterol, 7-Ketocholesterol,Exacerbates Imiquimod-Induced Psoriasis-like Dermatitis in Steatohepatitic Mice

Patients with psoriasis are at a higher risk of developing nonalcoholic fatty liver disease. We previously identified an oxidized derivative of cholesterol, 7-ketocholesterol (7KC), in diet-induced steatohepatitic mice. Here, we investigated whether 7KC exacerbates psoriasis-like dermatitis by accelerating steatohepatitis in mice. A high-fat/high-cholesterol/high-sucrose/bile salt diet (nonalcoholic steatohepatitis (NASH) diet) with or without 0.0125% 7KC was fed to C57BL/6 mice (7KC or control group) for three weeks to induce steatohepatitis. A 5% imiquimod cream was then applied to the ears and dorsal skin for four days to induce psoriasis-like dermatitis. Hepatic lipid accumulation and inflammatory cell infiltration were exacerbated in the 7KC group compared with the control group after three weeks. Serum tumor necrosis factor-α (TNF-α) levels were also elevated in the 7KC group (108.5 ± 9.8 vs. 83.1 ± 13.1 pg/mL, p < 0.005). Imiquimod cream increased the psoriasis area severity index (PASI) score in mice in the 7KC group (9.14 ± 0.75 vs. 5.17 ± 1.17, p < 0.0001). Additionally, Tnfa, Il23a, Il17a, and Il22 mRNA levels in the dorsal lesion were significantly upregulated. Finally, Th17 cell differentiation and the TNF signaling pathway were enhanced in the dorsal lesions and liver of mice in the 7KC group. These data suggest that steatohepatitis and psoriasis are linked by a potent, diet-related factor.     

High performance electron negative resist,chloromethylated polystyrene. A study on molecular parameters

High sensitivity and high contrast electron negative resist, chloromethylated polystyrene (CMS) was developed for direct writing electron beam lithography with 1-μm resolution. The resist shows excellent lithographic performances such as high plasma-etching durability and negligible “post polymerization effect”. A series of CMS covering a wide range of M?_w, 6,800–560,000, were synthesized by the chloromethylation of nearly monodisperse polystyrenes. The effects of molecular parameters on sensitivity and resolution were investigated. The chloromethylation remarkably improved the reactivity of polystyrene, but which was saturated above 40% of chloromethylation ratio. About 100 times higher sensitivity could be achieved as compared with the starting material. As the increase of chloromethylation ratio (CR) gradually broadened the molecular weight distribution (MWD), the optimum CR was evaluated to be about 40%. In the above range of M?_w, the sensitivity varies from 39 to 0.4 μC/cm, whereas the γ-value varies from 3.0 to 1.4. A sharp edge profile was obtained in developed pattern of CMS resist because of its relatively high glass-transition temperature (68–115°C) compared with commercial resists and the suitable selection of a developer. The resolution of CMS was compared with the structually related polymers synthesized from polystyrene with a broader MWD or vinylbenzylchloride and poly(chloroethylvinylether) (CEVE). These polymers show significantly lower resolution than CMS, which indicates the importance of MWD and T_g in electron negative resist.     

Benzopyrazine-fused tetracene derivatives: Thin-film formation at the crystalline mesophase for solution-processed hole transporting devices

Benzopyrazine-fused tetracene (TBPy) and its disulfide (TBPyS) bearing alkoxy groups (OCH₃, OC₈H₁₇) were designed and synthesized to obtain π-expanded tetracene derivatives. These derivatives are featured with long-wavelength light absorption property (λ_onset: up to 820 nm), photooxidative stability (half-lives (τ_1/2): 11 times longer than tetracene), and solubility for solution process. The methoxy compounds (TBPy-C1 and TBPyS-C1) were used for single-crystal X-ray crystallographic analysis and single-crystal organic field-effect transistor (OFET) devices showing relationship between packing structures and hole mobilities. The octyloxy compounds (TBPy-C8 and TBPyS-C8) were investigated on solution-processed thin-film formation and hole transport property in thin-film OFET devices. Crystalline mesophase of TBPy-C8 and TBPyS-C8 was characterized by differential scanning calorimetry analysis showing endothermic peaks at 98 and 198 °C on its second heating process and exothermic peaks at 177 and 76 °C on its second cooling process for TBPyS-C8, and played crucial roles in thin-films formation. Hole mobility of 1.7 × 10^?2 cm²/V s (with V_th = ?30 V and I_ON/I_OFF = 10⁴) was obtained for the thin-film OFET device of TBPyS-C8.     

X-ray CT observation of a “mosaic-tiling” structure and a “worm-like” structure in the ternary polymer blends

Two novel phase-separation morphology are reported in the ternary polymer blends of poly(propylene)/nylon-12/poly(lactic acid) by utilizing a high-contrast X-ray computerized tomography. One is a “mosaic-tiling” structure, where each of three components forms equally-sized droplets in a three-dimensional tessellation manner. The other morphology is a “worm-like” structure. Two components of the three form successive droplets like stripe socks. These results strongly suggest the wide variety of the phase-separation morphologies in ternary polymer blends.     

Adsorption characteristics of various proteins to a titanium surface

Adsorption characteristics of 18 proteins, with different sizes and isoelectric points, to a titanium oxide surface were studied. The adsorption isotherms were categorized based on protein type and pH: type 1, irreversible adsorption; type 2, Langmuir-type reversible adsorption; and type 3, reversible and irreversible adsorption. Most of the proteins tested were irreversibly adsorbed in the pH range of 3-8, whereas most adsorbed reversibly at pH 8.5-9.4. Protamine, with a pI value of 12, adsorbed reversibly in the pH range of 3-9. pH values that gave maximal sums of irreversibly and reversibly adsorbed proteins were in the pH range of 3-8 and tended to increase slightly with the pI value of the corresponding protein. pH values that gave maximal quantities of irreversibly adsorbed protein ranged between 4-6 and were nearly independent of pI.     

Temperature effects on positive electron resists irradiated with electron beam and deep-UV light

The exposure characteristics of poly(methyl methacrylate) (PMMA) and poly(methyl isopropenyl ketone) (PMIPK) were studied with electron beam and deep-UV light irradiation at different temperatures (20–160°C). The sensitivities and γ(contrast) values for electron beam irradiation show small temprature effects, but those for deep-UV light irradiation revel relatively large temperature effects. The result in which γ (contrast) values for the electron beam irradiation as a whole are significantly larger than for the deep-UV light irradiation is related to the molecular weight dispersity of irradiated resists. The result in which γ(contrast) for PMMA is larger than that for PMIPK at given development conditions is also related to the molecular weight ratios of the original and irradiated resists. The thickness reduction and negative inversion (crosslinking) compete under a large dose of electron beam irradiation, but the latter is scarcely apparent under deep-UV irradiation. The PMMA sensitivity for deep-UV irradiation diminishes in O₂ gas flow compared with the irradiation in N₂ gas flow, but PMIPK sensitivity is not influenced by O₂. From these results, the different decomposition mechanisms are discussed.