Enhanced intestinal absorption of vancomycin with Labrasol and d-α-tocopheryl PEG 1000 succinate in rats

Prasad, Y. V. Rama; Puthli, Shivanand P.; Eaimtrakarn, Sudarat; Ishida, M.; Yoshikawa, Yukako; Shibata, Nobuhito; Takada, Kanji

doi:10.1016/s0378-5173(02)00544-6

Cited by 109 publications

(49 citation statements)

References 25 publications

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“…5,6 Microemulsions also have the potential to increase the permeability of hydrophilic peptides and proteins across the intestinal mucosa, thus enhancing their bioavailability. 7,8 One of the proposed mechanisms involves enhancer-induced structural and fluidity changes in the mucosal membrane. 9 However, there are few reports on the enhancing effect of water-in-oil (w/o) microemulsions on Biopharmaceutics Classification System (BCS) III low molecular weight drugs.…”

Section: Introductionmentioning

confidence: 99%

Enhanced effect and mechanism of water-in-oil microemulsion as an oral delivery system of hydroxysafflor yellow A

Zhuang²,

Wu³

et al. 2011

IJN

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Background: A microemulsion is an effective formulation for improving the oral bioavailability of poorly soluble drugs. In this paper, a water-in-oil (w/o) microemulsion was investigated as a system for enhancing the oral bioavailability of Biopharmaceutic Classification System (BCS) III drugs. Methods: The microemulsion formulation was optimized using a pseudoternary phase diagram, comprising propylene glycol dicaprylocaprate (PG), Cremophor ® RH40, and water (30/46/24 w/w). Results: The microemulsion increased the oral bioavailability of hydroxysafflor yellow A which was highly water-soluble but very poorly permeable. The relative bioavailability of hydroxysafflor yellow A microemulsion was about 1937% compared with a control solution in bile duct-nonligated rats. However, the microemulsion showed lower enhanced absorption ability in bile duct-ligated rats, and the relative bioavailability was only 181%. In vitro experiments were further employed to study the mechanism of the enhanced effect of the microemulsion. In vitro lipolysis showed that the microemulsion was digested very quickly by pancreatic lipase. About 60% of the microemulsion was digested within 1 hour. Furthermore, the particle size of the microemulsion after digestion was very small (53.3 nm) and the digested microemulsion had high physical stability. An everted gut sac model demonstrated that cumulative transport of the digested microemulsion was significantly higher than that of the diluted microemulsion. Conclusion: These results suggested that digestion of the microemulsion by pancreatic lipase plays an important role in enhancing oral bioavailability of water-soluble drugs.

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Section: Introductionmentioning

confidence: 99%

Enhanced effect and mechanism of water-in-oil microemulsion as an oral delivery system of hydroxysafflor yellow A

Zhuang²,

Wu³

et al. 2011

IJN

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“…In addition, Labrasol is known to enhance the intestinal absorption of drugs. 32) Thus we selected Labrasol as the surfactant. Among the co-surfactants tested in this study, Transcutol P presented the highest drug solubility (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Formulation and <i>in Vitro</i> Characterization of a Novel Solid Lipid-Based Drug Delivery System

Chu

Itagaki³

et al. 2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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The liquid self-emulsifying drug delivery system (L-SEDDS), commonly used to deliver effective but poorly water-soluble oleanolic acid (OA), has many limitations such as high manufacturing costs, few choices of dosage forms, risk of leakage from hard gelatin capsules, low stability, limited portability, incompatibility with capsule materials, and relatively restricted storage conditions. Thus the main purpose of our study was to develop a promising solid lipid-based drug delivery system (S-SEDDS) for OA. The S-SEDDS, prepared from wet granulation with an optimized L-SEDDS formulation and mannitol, was characterized by particle size analysis, scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction. Finally, the solubility of the OA-loaded S-SEDDS was compared with that of OA powder in the dissolution assay. Our new S-SEDDS for OA was developed from the optimum L-SEDDS with ethyl oleate (oil phase), Labrasol (surfactant), and Transcutol P (cosurfactant) at a volume ratio of 15 : 71 : 14 with 1.5% w/v OA and mannitol. The dissolution of OA was improved by 60% compared with that of the pure OA powder. All the problems associated with the L-SEDDS were resolved. The methodologies we developed for OA delivery could also be utilized for the delivery of other drugs with the S-SEDDS.

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“…Therefore the enhanced concentrations of alpha tocopherol above 1% lead to the rapid in vitro release of drug in initial hours and had no effect on in vitro dissolution behavior of drug. The f 1 and f 2 factors suggests that twelve out of sixteen runs were similar to reference with f 2 value between 50-100 and Run 2 to be more bioavailable and may result in enhanced absorption from the gastrointestinal tract as evidenced by use of D-α-tocopheryl PEG 1000 succinate (TPGS), a derivative of vitamin E that has a relatively low critical micelle concentration and has been found to increase the oral absorption of drugs including vancomycin through micelle formation [11]. For hydrophobic drugs, increased wettability upon exposure to biological fluids may lead to improved dissolution thereby enhanced bioavailability that was in turn evidenced from the pharmacokinetic parameters where there was marked improvement in bioavailability *t indicates the significant difference at 5% level rate and extent compared to the pure drug.…”

Section: Test For Comparison Of Means Of Reference and Optimized Tagumentioning

confidence: 87%

Enhancement of Bioavailability of Fenofibrate with Alpha Tocopherol and Phospholipids as Solubilizers

Indira¹

2012

JBB

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The purpose of this study was to investigate the effect of different solubilizers namely alpha tocopherol, soy phosphatidylcholine 70, Phospholipon 80H, and Phospholipon 90H on the bioavailability of sustained release fenofibrate pellets using fluid bed coating by applying Taguchi design to optimize the type and concentration of solubilizer at four levels namely 0.5%, 1%, 1.5%, and 2%. The pellets were prepared by loading the fenofibrate blended with other excipients onto the core sugar pellets with the aid of the binder solution. Taguchi experimental runs with alpha tocopherol 1% and Phospholipon 90H 2% (test) showed significant differences in in vitro dissolution behavior of drug compared to the pure drug. The pharmacokinetics of pure drug and test was evaluated in healthy male Wistar rats and found that t 1/2 was reduced significantly (4.36 and 4.02 hours) while AUC 0-t (32.14 ± 6.38 μg h/ml, 36.94 ± 6.2 μg h/ml), C max (8.7 ± 2.31 μg/ml, 9.8 ± 2.2 μg/ml) were improved markedly compared to the pure drug with t 1/2 (7.339314 ± 3.1 hours), AUC 0-t (11.89 ± 8.13 μg h/ml), and C max (5.137 ± 3.37 μg/ml). The extent of the mean plasma exposure of fenofibrate was 2.7 and 3.1 fold higher in animals treated with test. The ANOVA results revealed that type and concentration of solubilizer are crucial for enhancement of in vitro dissolution profile. Hence use of solubilizers may be the promising way to improve the oral bioavailability of fenofibrate. Enhancement of Bioavailability of MethodsDrug loading: Drug was loaded onto sugar spheres using fluidized bed processor . The sugar spheres were loaded into the fluidized bed processor and warmed for about 10 -15 minutes. Binder solution was prepared by dissolving Povidone K30 and sugar in purified water under constant stirring. Unmicronized fenofibrate which was pre blended and pulverized (0.5 mm screen pulverizer) with other excipients was incorporated intermittently into the solution under constant stirring. The obtained solution was loaded onto the circulating sugar spheres (800 μm). The wet spheres were dried simultaneously during the process of circulation in wurster chamber. The process was continued till the complete solution was consumed. The various processing variables namely inlet air temperature (40-45°C), outlet air temperature (30-33°C), product temperature (36-40°C), chamber humidity (58-60%), air flow (85 m 3 /hr), compressed air pressure (1.5-3.0 kg/cm 2 )The peristaltic pump rpm (10-35) and spray rate (2 ml/min) were optimized in the preliminary trials.Design of experiment to optimize drug loaded fenofibrate pellets: Taguchi L16 design of experiment was used to study the effect of two variables namely, type of solubilizer and concentration of solubilizer at four different levels as given in Table 1 and Table 2. All the experimental runs were analyzed using Minitab statistical software package (version 15). Characterization methodsInfrared Spectroscopy analysis of drug and excipients: FT-IR spectra were obtained using FT-IR spectrometer (Model Nic...

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Enhanced intestinal absorption of vancomycin with Labrasol and d-α-tocopheryl PEG 1000 succinate in rats

Cited by 109 publications

References 25 publications

Enhanced effect and mechanism of water-in-oil microemulsion as an oral delivery system of hydroxysafflor yellow A

Enhanced effect and mechanism of water-in-oil microemulsion as an oral delivery system of hydroxysafflor yellow A

Formulation and <i>in Vitro</i> Characterization of a Novel Solid Lipid-Based Drug Delivery System

Enhancement of Bioavailability of Fenofibrate with Alpha Tocopherol and Phospholipids as Solubilizers

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