Synergy Effect of Plasmonic Field Enhancement and Light Confinement in Mesoporous Titania-Coated Aluminum Nanovoid Photoelectrode.

Photoelectrochemical (PEC) water splitting is a highly demanded technology for the realization of sustainable society. Various types of photoanodes have been developed to achieve high efficiency of PEC water splitting. Plasmonic field enhancement and light confinement effects are often adopted to improve PEC performance. However, their synergistic effects have not been studied. In this work, a mesoporous TiO2 layer was deposited on an Al plate with a nanovoid array structure, which acts as a photoanode and simultaneously exhibits a light confinement effect and surface plasmon resonance. The solo and synergy effects were investigated through experimental photocurrent measurements and theoretical simulations using the finite-difference time-domain method. The highest improvement in PEC performance was confirmed when the synergy effect occurred.

Theoretical evaluation of supersaturation of amorphous solid dispersion formulations with different drug/polymer combinations using mathematical modeling.

Amorphous solid dispersion (ASD) is a preparation widely used for improving the solubility and low oral absorbability of poorly water-soluble drugs, but the quantitative analysis of its dissolution profiles and its supersaturation status remains an important issue. We previously reported a new mathematical model for analyzing the dissolution characteristics of ASD preparations that enabled evaluation of theoretical solubility of ASDs and crystal precipitation rate constants of ASD preparations. In this study, to analyze the relationship between the mathematical parameters of the model and the dissolution behavior in detail, we simulated the dissolution behaviors upon changing parameters. We quantitatively evaluated the supersaturation of ASD preparations composed of various combinations of two drugs (ibuprofen or indomethacin) and three polymers (polyvinylpyrrolidone (PVP), copovidone or hydroxypropylmethylcellulose (HPMC)). Based on parameter comparison, the difference in the peak of drug concentration between IB/PVP and IB/HPMC ASDs was found to be derived from precipitation rate constant, not the theoretical solubility. In addition, although IMC/PVP ASD had higher solubility than IMC/HPMC ASDs, HPMC could suppress crystal precipitation and maintain supersaturation at higher concentrations than IMC/PVP ASD by comparing parameters derived from model fitting. Thus, our results show that the use of mathematical parameters can illuminate theoretical mechanical information regarding dissolution behaviors of various ASDs and permit a visualization of the character of the dissolution process.

Analysis of available surface area can predict the long-term dissolution profile of tablets using short-term stability studies.

Generally, since at least 6 months are usually needed for accelerated testing of tablet at 40 °C/75% relative humidity (RH), it would be crucial important to predict the dissolution profiles during long-term storage period by using samples stored with shorter periods such as 3 months. In this study, we developed a new method for predicting changes in dissolution from tablets during long-term storage-based changes in the available surface area [S (t)]. In addition, we discussed the dissolution behavior and mechanisms using S (t). The results revealed drastic delays in dissolution in samples stored at 40 °C/75% RH for 7 weeks. Considering changes of S (t) patterns, this delay was derived from changes of the tablet surface. New parameters, namely T22.1 and T63.2, calculated from the S (t) profile tended to increase with an increased duration of testing. Concerning the long-term prediction model using short-term data, a nonlinear model was deemed appropriate because good agreement was observed between the value predicted using the model and the measured value for samples stored at 40 °C/75% RH for 6 months. Therefore, using the new evaluation method based on S (t), we can predict changes in dissolution during long-term storage using short-term methods.

Effects of tablet formulation and subsequent film coating on the supersaturated dissolution behavior of amorphous solid dispersions.

The effects of tablet preparation and subsequent film coating with amorphous solid dispersion (ASD) particles that were composed of a drug with poor water solubility and hydrophilic polymers were investigated. ASD particles were prepared with a drug and vinylpyrrolidone-vinyl acetate copolymer (PVPVA) or polyvinylpyrrolidone (PVP) at a weight ratio of 1:1 or 1:2 using a melt extrusion technique. Tablets were prepared by conventional direct compression followed by pan coating. A mathematical model based on the Noyes-Whitney equation assuming that stable crystals precipitated at the changeable surface area of the solid-liquid interface used to estimate drug dissolution kinetics in a non-sink dissolution condition. All the ASD particles showed a maximum dissolution concentration approximately ten times higher than that of the crystalline drug. The ASD particles with PVPVA showed higher precipitation rate with lower polymer ratio, while PVP did not precipitate within 960 min regardless of the polymer ratio, suggesting the ASD particles of 1:1 drug:PVPVA (ASD-1) were the most unstable among the ASD particles considered. The dissolution of a core tablet with ASD-1 showed less supersaturation and a much higher precipitation rate than those of ASD-1 particles. However, a film-coated tablet or core tablet with a trace amount of hydroxypropylmethylcellulose (HPMC) showed a similar dissolution profile to that of the ASD-1 particles, indicating HPMC had a remarkable precipitation inhibition effect. Overall, these results suggest that tablet preparation with ASD may adversely affect the maintenance of supersaturation; however, this effect can be mitigated by adding an appropriate precipitation inhibitor to the formulation.

Mathematical model to analyze the dissolution behavior of metastable crystals or amorphous drug accompanied with a solid-liquid interface reaction.

Metastable crystals and the amorphous state of poorly water-soluble drugs in solid dispersions (SDs), are subject to a solid-liquid interface reaction upon exposure to a solvent. The dissolution behavior during the solid-liquid interface reaction often shows that the concentration of drugs is supersaturated, with a high initial drug concentration compared with the solubility of stable crystals but finally approaching the latter solubility with time. However, a method for measuring the precipitation rate of stable crystals and/or the potential solubility of metastable crystals or amorphous drugs has not been established. In this study, a novel mathematical model that can represent the dissolution behavior of the solid-liquid interface reaction for metastable crystals or amorphous drug was developed and its validity was evaluated. The theory for this model was based on the Noyes-Whitney equation and assumes that the precipitation of stable crystals at the solid-liquid interface occurs through a first-order reaction. Moreover, two models were developed, one assuming that the surface area of the drug remains constant because of the presence of excess drug in the bulk and the other that the surface area changes in time-dependency because of agglomeration of the drug. SDs of Ibuprofen (IB)/polyvinylpyrrolidone (PVP) were prepared and their dissolution behaviors under non-sink conditions were fitted by the models to evaluate improvements in solubility. The model assuming time-dependent surface area showed good agreement with experimental values. Furthermore, by applying the model to the dissolution profile, parameters such as the precipitation rate and the potential solubility of the amorphous drug were successfully calculated. In addition, it was shown that the improvement in solubility with supersaturation was able to be evaluated quantitatively using this model. Therefore, this mathematical model would be a useful tool to quantitatively determine the supersaturation concentration of a metastable drug from solid dispersions.