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1.
Int J Pharm ; 564: 39-47, 2019 Jun 10.
Article in English | MEDLINE | ID: mdl-30981872

ABSTRACT

We investigated the effect of variation in the molecular weight of hypromellose (HPMC) on the oral absorption of fenofibrate (FFB) nanocrystal. Four types of HPMC with different molecular weights and sodium dodecyl sulfate (SDS) were used as dispersion stabilizers for FFB nanocrystal suspension. Wet-milling of FFB crystal with HPMC and SDS formed diamond-shaped FFB nanocrystals with approximately 150 nm diameter. HPMC was strongly adsorbed onto the FFB nanocrystal interface, and the amount of HPMC adsorbed was not dependent on the molecular weight of HPMC. However, the decrease in the molecular weight of adsorbed HPMC led to an improvement in the permeability of FFB nanocrystal through the mucin layer. The decrease in molecular weight of HPMC enhanced the flexibility of FFB nanocrystal interface and effectively inhibited its interaction with mucin. This led to faster diffusion of FFB nanocrystal through mucin. In vivo oral absorption studies showed rapid FFB absorption from FFB nanocrystal formulations using HPMC of low molecular weights. The present study revealed that the molecular weight of the dispersion stabilizer for drug nanocrystal formulation should be taken into consideration to achieve improved absorption of poorly water-soluble drugs after oral administration.


Subject(s)
Fenofibrate/chemistry , Hypolipidemic Agents/chemistry , Hypromellose Derivatives/chemistry , Mucins/chemistry , Nanoparticles/chemistry , Administration, Oral , Animals , Diffusion , Fenofibrate/blood , Fenofibrate/pharmacokinetics , Hypolipidemic Agents/blood , Hypolipidemic Agents/pharmacokinetics , Hypromellose Derivatives/pharmacokinetics , Intestinal Absorption , Male , Molecular Weight , Permeability , Rats, Sprague-Dawley , Sodium Dodecyl Sulfate/chemistry
2.
J Vac Sci Technol A ; 33(6): 061403, 2015 11.
Article in English | MEDLINE | ID: mdl-26339118

ABSTRACT

The authors investigate the effects of microwave annealing (MWA) on the recovery of plasma process-induced ion-bombardment damage in Si substrates. For damage creation, Ar discharges by a capacitively coupled plasma etcher are used. For damage repairing, the MWA or a rapid thermal annealing (RTA) are conducted. The authors employ spectroscopic ellipsometry (SE), photoreflectance spectroscopy (PRS), and capacitance-voltage (C-V) measurement to analyze the damaged structures. Recovery of the damage is discussed by comparing the obtained parameters before and after the annealing processes. In the SE analysis, the change in the real part of dielectric constant (Δεr) is investigated. The Δεr spectral peak around 3.4 eV decreases with an increase in the annealing temperature (Ta) for both MWA and RTA, indicating the decrease in the density of defects created in the Si substrate. In the PRS analysis, the spectral peak intensity is found to decrease by the plasma exposure, and then to increase with Ta, which implies the recovery of the Si crystalline structure by MWA as well as by RTA. In the C-V measurement, the voltage shift (ΔVb) in the respective C-V curves is used as a measure of the number of defects present in the surface and interface damaged regions. The ΔVb in the negative bias direction is observed after the plasma exposure for all damaged structures, while after annealing the ΔVb in the positive bias direction is confirmed, suggesting the recovery of the damage in the surface and interface regions. Moreover, it is experimentally found that MWA induces larger |ΔVb| than RTA. These findings indicate the decrease in carrier trap sites in the surface and interface regions of damaged structures, and that MWA is more effective in repairing such damage than RTA. The authors propose a model explaining these mechanisms where defect-induced dipole moments that interact with the incident microwave are considered. The present results draw a new damage-recovery picture by MWA, in particular, for plasma-induced damage in surface and interface regions of Si substrates.

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