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101.
《Asian Journal of Pharmaceutical Sciences》2018,13(6):546-554
Due to low solubility and bioavailability, atorvastatin calcium is confronted with challenge in
conceiving appropriate formulation. Solid dispersion of atorvastatin calcium was prepared
through the solvent evaporation method, with Poloxamer 188 as hydrophilic carriers. This
formulation was then characterized by scanning electron microscopy, differential scanning
calorimetry,powder X-ray diffraction and fourier transform infrared spectroscopy. Moreover,
all these studies suggested the conversion of crystalline atorvastatin calcium. In addition,
the drug solubility studies as well as dissolution rates compared with bulk drug and market
tablets Lipitor were also examined. Furthermore, the study investigated the pharmacokinetics
after oral administration of Lipitor and solid dispersion. And the AUC0–8 h and Cmax
increased after taking ATC-P188 solid dispersion orally compared with that of Lipitor. All
these could be demonstrated that ATC-P188 solid dispersions would be prospective means
for enhancing higher oral bioavailability of ATC. 相似文献
102.
目的 制备眼用温敏型小檗碱白蛋白纳米粒原位凝胶(Ber-BSA-NPs-Gel),并对其理化性质进行初步研究。方法 以泊洛沙姆407(F127)和泊洛沙姆188(F68)为凝胶基质,以凝胶胶凝温度为考察指标对处方进行优化;去溶剂化法制备小檗碱白蛋白纳米粒(Ber-BSA-NPs),冷溶法制备Ber-BSA-NPs-Gel;使用NDJ—1型黏度计测定凝胶黏度;以模拟泪液为释放介质、UV法考察凝胶的体外释放特性。结果 经过处方优化,确定原位凝胶基质的处方为26% F127和4% F68,优化处方在30.9 ℃为自由流动的液体,经泪液稀释后在34.2 ℃能够发生相变形成凝胶。体外释放结果表明Ber-BSA-NPs-Gel具有较好的缓释作用。结论 制备得到的眼用温敏凝胶符合眼部应用要求,具有良好的应用前景。 相似文献
103.
Pallashri Saha Atul Katarkar Bornita Das Aritra Bhattacharyya 《Pharmaceutical biology》2016,54(9):1606-1615
Context The effect of 6-gingerol (6G), the bioactive component of Zingiber officinale Roscoe (Zingiberaceae), in the reduction of Vibrio cholerae (Vibrionaceae)-induced inflammation has not yet been reported.Materials and methods Cell viability assay was performed to determine the working concentration of 6G. Elisa and RT-PCR were performed with Int 407 cells treated with 50?μM 6G and 100 multiplicity of infection (MOI) V. cholerae for 0, 2, 3, 3.5, 6 and 8?h to determine the concentration of IL-8, IL-6, IL-1α and IL-1β in both protein and RNA levels. Furthermore, the effect of 50?μM 6G on upstream MAP-kinases and NF-κB signalling pathways was evaluated at 0, 10, 15, 30, 60 and 90?min.Results The effective dose (ED50) value of 6G was found to be 50?μM as determined by cell viability assay. Pre-treatment with 50?μM 6G reduced V. cholerae infection-triggered levels of IL-8, IL-6, IL-1α and IL-1β by 3.2-fold in the protein level and two-fold in the RNA level at 3.5?h. The levels of MAP-kinases signalling molecules like p38 and ERK1/2 were also reduced by two- and three-fold, respectively, after 30?min of treatment. Additionally, there was an increase in phosphorylated IκBα and down-regulation of p65 resulting in down-regulation of NF-κB pathway.Conclusion Our results showed that 6G could modulate the anti-inflammatory responses triggered by V. cholerae-induced infection in intestinal epithelial cells by modulating NF-κB pathway. 相似文献
104.
The objectives of the current study were to characterize the pharmacokinetic profile of dronedarone in the rat, and to examine the effect of hyperlipidemia on its pharmacokinetics. Single doses of dronedarone were administered to rats intravenously (4 mg/kg), orally (55 mg/kg) and intraperitoneally (65 mg/kg). To induce hyperlipidemia, some of the rats were administered intraperitoneal doses of poloxamer 407 before giving an oral dose of dronedarone. After intravenous doses of 4 mg/kg dronedarone, plasma clearance and volume of distribution at steady‐state were 25.1 ± 8.09 mL/min/kg and 10.8 ± 4.77 L/kg, respectively. After oral doses the maximum plasma concentrations (Cmax) and their median time of attainment (tmax) were 1.87 ± 1.65 mg/mL and 3.5 h, respectively. Intraperitoneal administration of 65 mg/kg dronedarone base yielded plasma Cmax and median tmax of 0.816 ± 0.611 mg/mL and 3 h, respectively. Protein binding was high in NL and HL plasma. Dronedarone is extensively distributed with high volume of distribution in the rat. The drug showed poor bioavailability (<20%) after oral and intraperitoneal administration. The increased plasma concentrations after oral dosing to hyperlipidemic rats appears to be attributable to a direct effect on metabolizing enzymes or transport proteins. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
105.
106.
Carbamazepine (CBZ), indicated for the control of epilepsy, undergoes extensive hepatic first-pass elimination after oral administration. A rectal dosage form of CBZ is not commercially available, although it is of particular interest when oral administration is impossible. Conventional suppositories can cause patient discomfort and may reach the end of the colon; consequently, the drug can undergo the first-pass effect. Mucoadhesive liquid suppositories of CBZ were prepared by adding carbopol to formulation of thermally gelling suppositories that contain 20% poloxamer 407 and either 15% poloxamer 188 or 1% methylcellulose. Gellan gum was also tried instead of 20% poloxamer. All formulations contained 10% CBZ. The characteristics of the suppositories differed depending on the formulation. The formula containing 20% poloxamer 407, 1% methylcellulose, and 0.5% carbopol showed reasonable gelation temperature, gel strength and bioadhesive force. The analysis of release mechanism showed that CBZ released from the suppositories by Fickian diffusion. In vivo evaluation of the same formulation showed higher peak plasma concentration of CBZ compared with the orally administered suspension containing the equivalent amount of drug. However, there was no statistical significant difference (p > 0.05) in extent of bioavailability between the liquid suppository and oral suspension as indicated by the values of AUC0 - ∝, 17.9 and 18.8 μ g.h/ml, respectively. These results suggested that mucoadhesive in situ gelling liquid suppository could be an effective and convenient delivery system of carbamazepine. 相似文献
107.
Chiappetta DA Facorro G de Celis ER Sosnik A 《Nanomedicine : nanotechnology, biology, and medicine》2011,7(5):624-637
This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly(ethylene oxide)-poly(propylene oxide) for the more effective encapsulation of the anti-HIV drug efavirenz. The co-micellization process of 10% binary systems combining different weight ratios of a highly hydrophilic poloxamer (Pluronic F127) and a more hydrophobic poloxamine counterpart (Tetronic T304 and T904) was investigated by means of dynamic light scattering, cloud point and electronic spin resonance experiments. Then, the synergistic solubilization capacity of the micelles was shown. Findings revealed a sharp solubility increase from 4 μg/ml up to more than 33 mg/ml, representing a 8430-fold increase. Moreover, the drug-loaded mixed micelles displayed increased physical stability over time in comparison with pure poloxamine ones. Overall findings confirmed the enormous versatility of the poloxamer/poloxamine systems as Trojan nanocarriers for drug encapsulation and release by the oral route and they entail a relevant enhancement of the previous art towards a more compliant pediatric HIV pharmacotherapy.
From the Clinical Editor
In this study, the authors demonstrate the versatility of poloxamer/poloxamine systems as Trojan nanocarriers for anti-HIV drug encapsulation and release by the oral route. A highly relevant stability and solubility enhancement is shown, which may ultimately lead to more compliant anti-HIV pharmacotherapy. 相似文献108.
109.
Vibrio cholerae, a noninvasive enteric bacterium, causing inflammatory diarrheal disease cholera, is associated with the secretion of proinflamammatory cytokines including IL-1β in cultured epithelial cells. Incubation of Int407 with live V. cholerae resulted in increased IL-1β mRNA expression as early as 2 h of infection, reached a peak at 3.5 h and decreased thereafter. The identity of the effector molecule(s) is largely unknown. The bacterial culture supernatant showed IL-1β stimulating activity. An engineered aflagellate V. cholerae flaA mutant (O395FLAN) resulted in highly reduced level of IL-1β expression in Int407. The crude flagellar protein of V. cholerae as well as recombinant FlaA induced IL-1β expression in Int407. Infection of Toll-like receptor 5 (TLR5) transfected HeLa cells with O395FLAN showed reduced expression of IL-1β compared to wild-type. Unlike wild-type V. cholerae, O395FLAN did not activate the NF-κB while the recombinant flagellin could activate NF-κB. Finally, the mitogen activated protein kinases (ERK1 and 2, p38) were phosphorylated in wild-type and recombinant flagellin treated Int407 cells and inhibition of the p38 and ERK pathways significantly decreased the IL-1β response induced by wild-type V. cholerae as well as recombinant flagellin. Our data clearly indicate that flagellin of V. cholerae could induce IL-1β expression by recognizing TLR5 that activate NF-κB and MAP kinase in Int407. 相似文献
110.
Solutions of non-ionic surfactants were prepared in water and buffer. The osmotic behavior of these solutions were studied by measuring their osmolality, using the freezing point depression method. Graphical representation of osmolality versus concentration depicted non-linear parabolic curves that were applied to logarithmic and polynomial mathematical models. One such surfactant, poloxamer 407, was selected and studied in solutions of water and buffer. We observed curves of similar profile, which were attributed to its interaction and association in aqueous solution. In the liquid state the osmotic influence is due to the surfactant-water interaction. When the solution is warmed and converted to the gel state, the polymer is taken out of play and the osmotic influence is due to the aqueous solution only. This phenomenon was supported by in vitro red blood cell tonicity observations. 相似文献