Transepidermal Potential of the Stretched Skin.

The electrical response of the skin to mechanical stretches is reported here. The electrical potential difference across the epidermis, i.e., transepidermal potential (TEP) of porcine skin samples subjected to cyclic stretching, was measured in real time to observe electrochemical change in epidermal tissue. In addition to a conventional method of TEP measurement for the whole of skin sample, a probe-type system with a fine-needle salt bridge was used for direct measurement of TEP at a targeted local point of the skin. TEP decreased with the increased mechanical stretches, and the change of TEP was found to be mostly occurred in the epidermis but not dermis nor hypodermis by comparing the results of conventional and the probe-type methods. The observed change of TEP value was quick, reversible, and strain-dependent. Considering from such characteristic behaviors, one of the possible mechanisms of the modulation of TEP would be influence of the streaming potential caused by the fluid flow during the physical deformation of the epidermis.

Red light-promoted skin barrier recovery: Spatiotemporal evaluation by transepidermal potential.

The light-promoted recovery of epidermal barrier of skin was evaluated by the associated recovery of transepidermal potential (TEP), the potential difference between the surface and dermis of skin, by using porcine skin samples. An accelerated recovery of TEP was observed by irradiation of red light with the irradiance of 40 mW/cm2 and a duration of > 10 min. The influence of the light stimulation to the surroundings (~ 20 mm) was also observed. The irradiations of blue and purple lights were ineffective in accelerating the barrier recovery. These characteristics of the light stimulation would be useful for the design of effective and safe phototherapy devices for skin. The present study proves that the TEP can serve as a spatiotemporal indicator of the epidermal barrier function.

Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine.

Amorphous solid dispersions are used as a strategy to improve the bioavailability of poorly water-soluble compounds. When formulating with a polymer, it is important not only for the polymer to stabilize against crystallization in the solid state, but also to improve the dissolution profile through inhibiting crystallization from the supersaturated solution generated by dissolution of the amorphous material. In this study, the dissolution profiles of solid dispersions of felodipine formulated with poly(vinylpyrrolidone) (PVP), hydroxypropyl methylcellulose (HPMC) or hydroxypropyl methylcellulose acetate succinate (HPMCAS) were compared. In addition, concentration versus time profiles were evaluated for the supersaturated solutions of felodipine in the presence and absence of the polymers. HPMCAS was found to maintain the highest level of supersaturation for the greatest length of time for both the dissolution and solution crystallization experiments, whereas PVP was found to be the least effective crystallization inhibitor. All polymers appeared to reduce the crystal growth rates of felodipine at an equivalent supersaturation and this mechanism most likely contributes to the enhanced solution concentration values observed during dissolution of the amorphous solid dispersions.

Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine.

The ability of various polymers to inhibit the crystallization of amorphous felodipine was studied in amorphous molecular dispersions. Spin-coated films of felodipine with poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), and hydroxypropylmethylcellulose (HPMC) were prepared and used for measurement of the nucleation rate and to probe drug-polymer intermolecular interactions. Bulk solid dispersions were prepared by a solvent evaporation method and characterized using thermal analysis. It was found that each polymer was able to significantly decrease the nucleation rate of amorphous felodipine even at low concentrations (3-25% w/w). Each polymer was found to affect the nucleation rate to a similar extent at an equivalent weight fraction. For HPMC and HPMCAS, thermal analysis indicated that the glass transition temperature (T(g)) of the solid dispersions were not significantly different from that of felodipine alone, whereas an increase in T(g) was observed for the PVP containing solid dispersions. Infrared spectroscopic studies indicated that hydrogen bonding interactions were formed between felodipine and each of the polymers. These interactions were stronger between felodipine and PVP than for the other polymers. It was speculated that, at the concentrations employed, the polymers reduce the nucleation rate through increasing the kinetic barrier to nucleation.

Ability of different polymers to inhibit the crystallization of amorphous felodipine in the presence of moisture.

PURPOSE: To investigate the ability of various polymers to inhibit the crystallization of amorphous felodipine from amorphous molecular dispersions in the presence of absorbed moisture. METHODS: Spin coated films of felodipine with poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydroxypropylmethylcellulose (HPMC) were exposed to different storage relative humidities and nucleation rates were measured using polarized light microscopy. Solid dispersions were further characterized using differential scanning calorimetry, infrared spectroscopy and gravimetric measurement of water vapor sorption. RESULTS: It was found that the polymer additive reduced nucleation rates whereas absorbed water enhanced the nucleation rate as anticipated. When both polymer and water were present, nucleation rates were reduced relative to those of the pure amorphous drug stored at the same relative humidity, despite the fact that the polymer containing systems absorbed more water. Differences between the stabilizing abilities of the various polymers were observed and these were explained by the variations in the moisture contents of the solid dispersions caused by the different hygroscopicities of the component polymers. No correlations could be drawn between nucleation rates and the glass transition temperature (Tg) of the system. PVP containing solid dispersions appeared to undergo molecular level changes on exposure to moisture which may be indicative of phase separation. CONCLUSIONS: In conclusion, it was found that for a given storage relative humidity, although the addition of a polymer increases the moisture content of the system relative to that of the pure amorphous drug, the crystallization tendency was still reduced.

Recrystallization of nifedipine and felodipine from amorphous molecular level solid dispersions containing poly(vinylpyrrolidone) and sorbed water.

PURPOSE: To compare the physical stability of amorphous molecular level solid dispersions of nifedipine and felodipine, in the presence of poly(vinylpyrrolidone) (PVP) and small amounts of moisture. METHODS: Thin amorphous films of nifedipine and felodipine and amorphous molecular level solid dispersions with PVP were stored at various relative humidities (RH) and the nucleation rate was measured. The amount of water sorbed at each RH was measured using isothermal vapor sorption and glass transition temperatures (Tg) were determined using differential scanning calorimetry. The solubility of each compound in methyl pyrrolidone was measured as a function of water content. RESULTS: Nifedipine crystallizes more easily than felodipine at any given polymer concentration and in the presence of moisture. The glass transition temperatures of each compound, alone and in the presence of PVP, are statistically equivalent at any given water content. The nifedipine systems are significantly more hygroscopic than the corresponding felodipine systems. CONCLUSIONS: Variations in the physical stability of the two compounds could not be explained by differences in Tg. However, the relative physical stability is consistent with differences in the degree of supersaturation of each drug in the solid dispersion, treating the polymer and water as a co-solvent system for each drug compound.

A comparison of the physical stability of amorphous felodipine and nifedipine systems.

PURPOSE: The objective of this study was to investigate thermodynamic and kinetic factors contributing to differences in the isothermal nucleation rates of two structurally related calcium channel blockers, nifedipine and felodipine, both alone and in the presence of poly(vinylpyrrolidone) (PVP). MATERIALS AND METHODS: Thin films of amorphous systems were cast onto glass slides and the nucleation rate was determined using optical microscopy. Enthalpy, entropy, and free energy of crystallization of the pure compounds were measured using differential scanning calorimetery (DSC). Molecular mobility and glass transition temperature of each amorphous system were characterized using DSC and hydrogen bonding patterns were analyzed with infrared spectroscopy. The composition dependence of the thermodynamic activity of the amorphous drug in the presence of the polymer was estimated using Flory-Huggins lattice theory. RESULTS: Nifedipine crystallized more readily than felodipine from the metastable amorphous form both alone and in the presence of PVP despite having a similar glass transition temperature and molecular mobility. Nifedipine was found to have a larger enthalpic driving force for crystallization and a lower activation energy for nucleation. CONCLUSIONS: The properties of the metastable form alone did not explain the greater propensity for nifedipine crystallization. When considering the physical stability of amorphous systems, it is important to also consider the properties of the crystalline counterpart.