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71.
In an effort to improve the bioavailability of the insoluble drug indomethacin, three complexes were prepared with indomethacin and the soluble complexing agents β-, hydroxyethyl-β-, and hydroxypropyl-β-cyclodextrin. The indomethacin content was similar among the complexes (P≤0.05). To confirm complex formation, each complex was characterized by ultraviolet, infrared, nuclear-magnetic resonance, powder X-ray diffraction, and differential-scanning calorimetry techniques. Powder diffraction studies show the β-cyclodextrin complex was polycrystalline, and the hydroxyethyl- and hydroxypropyl-β-cyclodextrin complexes were amorphous. Phase-solubility analysis confirmed the formation of complexes and suggested the three complexes were bound similarly. Solubility studies show complexation increased indomethacin solubility, and the hydroxyethyl- and hydroxypropyl-β-cyclodextrin complexes were more soluble than the β-cyclodextrin complex in 0.1N hydrochloric acid and distilled water. Dosage forms were prepared by encapsulating the complexes without the addition of excipients. Dissolution studies show the encapsulated β- and hydroxyethyl-β-cyclodextrin complexes had superior dissolution when compared to the hydroxypropyl-β-cyclodextrin and Indocin® (50 mg) capsules. Bioavailability studies were performed by administering the indomethacin complex or Indocin capsules to male-albino, New Zealand rabbits. Indomethacin plasma-time concentration data fit best to a compartment-independent model for all capsule formulations. Bioavailability comparisons by ANOVA show no significant difference (P≤0.10) in the peak-plasma time and peak concentration among the capsule formulations. The area-under-the-curve for the β-cyclodextrin complex capsules was found to be significantly higher (P≤0.10) than all other capsule formulations. In conclusion, the bioavailabilty of indomethacin was improved by complexation with only β-cyclodextrin. No correlations were found among the bioavailability, solubility, and dissolution results. 相似文献
72.
Sharma A Pandey R Sharma S Khuller GK 《International journal of antimicrobial agents》2004,24(6):599-604
The present study was designed to evaluate the chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) (PLG) nanoparticles (NP) encapsulating three front-line antitubercular drugs (ATDs: rifampicin, RIF; isoniazid, INH and pyrazinamide, PZA) at 2/3rd therapeutic dose. PLG nanoparticles prepared by the double emulsion and solvent evaporation technique were administered orally at 2/3rd therapeutic dose to guinea pigs. A single oral administration of the formulation resulted in sustained drug levels in the plasma for 7-12 days and in the organs for 11-14 days with a significant improvement in mean residence time as well as drug bioavailability. The administration of PLG nanoparticles every 10 days (five doses) to Mycobacterium tuberculosis H(37)Rv infected guinea pigs led to undetectable bacilli in the organs, as did 46 conventional doses. Therefore, nanoparticle based antitubercular chemotherapy forms a sound basis for a reduction in dosing frequency and also offers the possibility of reducing the drug dosage. 相似文献
73.
Effects of heavy metals on earthworms along contamination gradients in organic rich soils 总被引:4,自引:0,他引:4
Lukkari T Taavitsainen M Väisänen A Haimi J 《Ecotoxicology and environmental safety》2004,59(3):340-348
Earthworm communities and metal (bio)availability to earthworms along contamination gradients was studied in order to support chemical analyses in risk assessment of metal contaminated soils. Earthworms were sampled in three metal contaminated areas with different habitat and soil properties in Finland. Earthworm and soil samples were collected at three distances (1, 2, and 4 km) from the emission sources. Earthworms were identified as to species and analyzed for heavy metals. Total soil metal concentrations were analyzed using an ultrasound-assisted extraction method and bioavailable metal fraction was estimated by acetic acid extraction. In two of the three areas studied, heavy metal concentrations close to the emission sources were high enough to have harmful effects on earthworms and their environments. In general, diversity, total numbers, and biomass of earthworms increased with increasing distance from the emission sources. When individuals were available for analyses close to the emission source, positive correlations between metal concentrations in the earthworms and those in the soils were observed. 相似文献
74.
Arnaud A Ramírez M Baxter JH Angulo AJ 《Clinical nutrition (Edinburgh, Scotland)》2004,23(6):1303-1312
BACKGROUND AND AIMS: Glutamine instability in liquid media suggests that evaluation of reasonable enteral nutrition sources of glutamine is needed. N-acetyl-l-glutamine offers no instability and no intolerance problems. This research was conducted to study the absorption and apparent digestibility of glutamine versus N-acetyl-l-glutamine. METHODS: Two pig models were used. (1) In a clamped jejunal loop experiment, we measured the concentrations of glutamine and N-acetyl-l-glutamine in the intestinal infused solutions, intestinal mucosa, and portal and peripheral blood. (2) In a feeding experiment, we determined their apparent digestibility. RESULTS: N-acetyl-l-glutamine ( approximately 76%) was slightly less absorbed than glutamine ( approximately 85%) from the intestinal lumen into mucosa, where it was not detected as intact molecule, suggesting almost complete hydrolysis during absorption. Virtually no intact N-acetyl-l-glutamine was observed in the blood compartments; glutamine from lumenal N-acetyl-l-glutamine had the same behavior as that from lumenal-free glutamine in portal and peripheral blood. The apparent ileal digestibility of N-acetyl-l-glutamine was lower than that of free glutamine, as N-acetyl-l-glutamine was probably retained in the intestinal lumen to a greater extent than glutamine. CONCLUSION: N-acetyl-l-glutamine appeared to be a good candidate for glutamine fortification of enteral nutrition formulas. 相似文献
75.
The purpose of this study was to investigate the nasal absorption of insulin from a carbopol-based nasal gel spray in rabbits. An insulin nasal gel was prepared by dispersing carbopol in distilled water, followed by the addition of insulin solution, then neutralization and viscosity adjustment. The nasal absorption of insulin from the gel, in conscious rabbits, was evaluated in comparison with absorption from an insulin solution. The absolute bioavailability of insulin from the nasal gel was studied using blood glucose level in comparison to intravenous injection. The insulin gel formulation produced a significant hypoglycemic response in rabbits, whereas no response was seen following administration of the insulin solution formulation. The bioavailability of insulin from the nasal gel formulation was 20.6% compared with the intravenous injection. The results of the present study suggest that the carbopol gel promotes the nasal absorption of insulin in rabbit model and due to its sprayability with commercially available spray pumps, could be considered as a preferred platform in nasal drug administration. 相似文献
76.
The objective of our study was to prepare and evaluate osmotic matrix (OM) tablets of diclofenac sodium (DS). In vitro studies were done on USPXXIV dissolution apparatus II in different release medium. Surface characteristics of coating films and osmotic contribution of OM tablets also were studied. In vivo evaluation was carried out in 6 healthy human volunteers using HPLC method to assay plasma samples, and the results were compared with the performance of fabricated matrix and two commercial tablets of DS. Through in vitro drug release kinetics, using regression coefficient analysis and Peppas equation, different pharmacokinetic parameters and relative bioavailability were determined. OM tablets were found to provide more prolonged and controlled therapeutic plasma DS levels and also showed improved bioavailability in comparison to fabricated matrix and commercial tablets studied. 相似文献
77.
Mobility,bioavailability, and toxic effects of cadmium in soil samples 总被引:10,自引:0,他引:10
Prokop Z Cupr P Zlevorova-Zlamalikova V Komarek J Dusek L Holoubek I 《Environmental research》2003,91(2):119-126
Total concentration is not a reliable indicator of metal mobility or bioavailability in soils. The physicochemical form determines the behavior of metals in soils and hence the toxicity toward terrestrial biota. The main objectives of this study were the application and comparison of three approaches for the evaluation of cadmium behavior in soil samples. The mobility and bioavailability of cadmium in five selected soil samples were evaluated using equilibrium speciation (Windermere humic aqueous model (WHAM)), extraction procedures (Milli-Q water, DMSO, and DTPA), and a number of bioassays (Microtox, growth inhibition test, contact toxicity test, and respiration). The mobility, represented by the water-extractable fraction, corresponded well with the amount of cadmium in the soil solution, calculated using the WHAM (r(2)=0.96, P<0.001). The results of the ecotoxicological evaluation, which represent the bioavailable fraction of cadmium, correlated well with DTPA extractability and also with the concentration of free cadmium ion, which is recognized as the most bioavailable metal form. The results of the WHAM as well as the results of extraction experiments showed a strong binding of cadmium to organic matter and a weak sorption of cadmium to clay minerals. 相似文献
78.
吲哚拉新控释片及其胶囊的生物利用度比较 总被引:2,自引:0,他引:2
本文比较了吲哚拉新控释片和普通胶囊在人体内生物利用度,吲哚拉新血浆浓度用高效液相色谱法(HPLC)测定。结果表明,在6名受试者中.两种制剂的吸收程及基本一致;但控释片的峰药浓度(Cmax)显著低于普通胶囊(P<0.01),其达峰时间(Tmax)也明显延迟(P<0.01)。给予单剂量(250mg)控释片后.在给药后4h至24h其血浆浓度显著高于普通胶囊(P<0.05)。说明该控释片可避免普通制剂初期的高峰血药浓度,从而降低副作用并延长了给药间隔时间。 相似文献
79.
马来酸依那普利片的药物动力学及相对生物利用度 总被引:7,自引:0,他引:7
10名健康志愿者随机交叉口服10mg国产和进口马来酸依那普利片后,采用高效液相色谱法测得血浆中依那普利浓度分别在(0.83±0.21)h和(0.85±0.17)h达到峰值(69.3±27.7)ng/ml和(71.3)±29.5)ng/ml。血药浓度曲线下面积(AUC0→8)分别为(121.4±39.0)h·ng/ml和(121.6±40.5)h·ng/ml。以进口片为参比,国产片的相对生物利用废为(100.6±8.4)%。经统计分析,两种制剂具有生物等效性。 相似文献
80.
Liangxing Tu Yueneng Yi Wei Wu Fuqiang Hu Kaili Hu Jianfang Feng 《International journal of pharmaceutics》2013
Puerarin, which is extracted from traditional Chinese medicine, is widely used in clinic in China and mainly used as a therapeutic agent to cardiovascular diseases. Owing to its poor water solubility and adverse drug reactions caused by cosolvents after intravenous administration, the development of oral formulation is urgently needed. Nowadays, nanocrystals technique has become a preferred way to develop oral dosage form. In this study, we used high pressure homogenization (HPH) to prepare puerarin nanocrystals and microcrystals with different sizes ranged from 525.8 nm to 1875.6 nm and investigated the influence of particle size on pharmacokinetics. The nanocrystals and microcrystals prepared were characterized using DLS, DSC, XRD and SEM, and we found that the crystalline state of puerarin was changed during the preparation process and the drug was dispersed into HPMC. In the pharmacokinetic study, we observed an increasing of Cmax and AUC and a decreasing of CL/F with the decreasing of particle size. The AUC of the puerarin nanocrystals (525.8 nm) was 7.6-fold of that of raw puerarin suspension, with an absolute bioavailability of 21.44%. From the above results, we can conclude that nanocrystal technique is an efficient technology to improve the oral bioavailability of puerarin. 相似文献