ABSTRACT
Donepezil hydrochloride thermosensitive in situ gel for nasal delivery was prepared by using Poloxamer 407 and Poloxamer 188 as thermoreversible polymers, hydroxypropyl-ß-cyclodextrin and ethylparaben as permeation enhancer and preservative, respectively. The gelation temperature and time, pH value of the gel formulation were found to meet the requirements for nasal administration. The in vitro erosion and in vitro release tests exhibited obvious drug sustained release behavior. Meantime, main pharmacokinetic parameters such as tmax, cmax and AUC in plasma as well as in brain were significantly different between the nasal gel formulation and intragastric drug solution in rats (p < 0.01). The relative bioavailability and drug targeting efficiency of the gel formulation were calculated to be 385.6 and 151.2 %, respectively. Thus, the drug gel formulation might be a potential new delivery system for treatment of Alzheimer's disease due to its higher bioavailability and better distribution to brain when compared to oral route.
Subject(s)
Donepezil/administration & dosage , Drug Delivery Systems , Nootropic Agents/administration & dosage , Administration, Intranasal , Animals , Area Under Curve , Delayed-Action Preparations , Donepezil/pharmacokinetics , Drug Carriers/chemistry , Drug Liberation , Excipients/chemistry , Gels , Hydrogen-Ion Concentration , Male , Nootropic Agents/pharmacokinetics , Rats , Rats, Sprague-Dawley , Temperature , Tissue DistributionABSTRACT
C3N6H6·2H3BO3 (M·2B) is a highly promising precursor of boron nitride (BN) fibers due to its eco-friendly and low-cost fabrication. However, it is still unclear why the fibers can maintain their morphology in spite of drastic weight loss (nearly 80 wt%) during M·2B-to-BN pyrolysis. Herein, an interesting cracking and self-healing behavior of the heated M·2B fibers was observed at initial pyrolysis. In situ formed molten boron oxide (B2O3) was figured out to be the healing agent for the cracks and subsequently merged into the continuous matrix enclosing melamine/melem molecules, which subsequently acted as a nitrogen source. The B2O3 matrix helped to keep the fiber morphology undamaged under the second weight-loss stage in the pyrolysis process. This strategy of taking advantage of the in situ formed molten phase for healing cracks offers detailed guidance to prepare defect-free M·2B-derived BN fibers and would be significant in defect repair for other ceramics.
ABSTRACT
The surface hydroxyls on SiC nanosheets provide local protons, stabilize intermediates and localize photogenerated electrons in the deep photoreduction of CO2, significantly promoting the efficiency and selectivity of CH4 yield. This study describes the surface reaction for selective CO2 reduction based on both thermodynamic and kinetic requirements.
ABSTRACT
Simvastatin is poorly bioavailable because it is practically insoluble in water and shows dissolution rate-limited absorption. Solubilizing effects of several ß-cyclodextrin (ßCD) derivatives such as HPßCD, SBEßCD and DMßCD on simvastatin in aqueous solution were investigated using the phase solubility technique. The solubility diagram of simvastatin with each ßCD derivative could be classified as AL-type, indicating soluble complex formation of 1:1 stoichiometry. Among the above ßCD derivatives DMßCD was found to be the ideal complexing agent for improving drug solubility. The simvastatin complex with DMßCD was prepared using the co-evaporation method and was then characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and in vitro dissolution. Dissolution and pharmacokinetic studies indicated that the simvastatin/DMßCD complex exhibited an increased dissolution rate, rapid absorption, and improved bioavailability in rats compared to free drug. Maximum plasma concentration (cmax) and the time to reach it (tmax) were 21.86 µg mL-1 and 1.4 h for the drug complex, 8.25 µg mL-1 and 3.0 h for free drug, respectively. Main pharmacokinetic parameters such as tmax, cmax were significantly different (p < 0.01) between the simvastatin complex and free drug. Bioavailability of the simvastatin complex relative to free drug was up to 167.0 %.
Subject(s)
Excipients/chemistry , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics , Simvastatin/pharmacokinetics , beta-Cyclodextrins/chemistry , 2-Hydroxypropyl-beta-cyclodextrin/chemistry , Animals , Biological Availability , Calorimetry, Differential Scanning , Chemistry, Pharmaceutical , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry , Male , Rats , Rats, Wistar , Simvastatin/administration & dosage , Simvastatin/chemistry , Solubility , Spectroscopy, Fourier Transform InfraredABSTRACT
The aim of this study was to prepare a nasal gel of risperidone and to investigate the pharmacokinetics and relative bioavailability of the drug in rats. Compared with oral dosing, the risperidone nasal gel exhibited very fast absorption and high bioavailability. Maximal plasma concentration (cmax) and the time to reach cmax (tmax) were 15.2 µg mL-1 and 5 min for the nasal gel, 3.6 µg mL-1 and 30 min for the oral drug suspension, respectively. Pharmacokinetic parameters such as tmax', cmax and AUC of oral and nasal routes were significantly different (p < 0.01). Relative bioavailability of the drug nasal preparation to the oral suspension was up to 1600.0 %. Further, the in vitro effect of the risperidone nasal gel on nasal mucociliary movement was also investigated using a toad palate model. The risperidone nasal formulation showed mild ciliotoxicity, but the adverse effect was temporary and reversible.
