Modulation of Intestinal P-Glycoprotein Function by Cremophor EL and Other Surfactants by an In Vitro Diffusion Chamber Method Using the Isolated Rat Intestinal Membranes

Shono, Yasushi; Nishihara, Hisayo; Matsuda, Y.; Furukawa, Shigeto; Okada, Naoki; Fujita, Takuya; Yamamoto, Akira

doi:10.1002/jps.20017

Cited by 150 publications

(78 citation statements)

References 17 publications

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“…19 Shono et al reported that nonionic surfactants including Cremophor EL and Tween 80 may be useful pharmaceutical excipients for inhibiting the function of P-gp to increase the intestinal absorption of various drugs that can be secreted by the P-gp-mediated efflux system in the intestine. 49 Therefore, the use of Cremophor EL in the NE increases the oral exposure of AG.…”

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confidence: 99%

Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide

Yen

Chen

et al. 2018

IJN

110

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Background Andrographolide (AG), a compound with low water solubility, possesses various pharmacological activities, particularly anti-inflammatory activity. However, its low oral bioavailability is a major obstacle to its potential use. This study developed and optimized an AG-loaded nanoemulsion (AG-NE) formulation to improve AG oral bioavailability and its protective effects against inflammatory bowel disease. Methods A high-pressure homogenization technique was used to prepare the AG-NE and solubility, viscosity, and droplet size tests were conducted to develop the optimized AG-NE composed of α-tocopherol, ethanol, Cremophor EL, and water. The permeability was assessed using everted rat gut sac method and in vivo absorption and anti-inflammatory effect in rats was also evaluated. The plasma concentration of AG was determined using our validated high performance liquid chromatography method, which was used to generate a linear calibration curve over the concentration range of 0.1–25 μg/mL in rat plasma ( R 2 >0.999). Results The optimized AG-NE had a droplet size of 122±11 nm confirmed using transmission electron microscopy and a viscosity of 28 centipoise (cps). It was stable at 4 and 25°C for 90 days. An ex vitro intestinal permeability study indicated that the jejunum was the optimal site for AG absorption from the optimized AG-NE, which was 8.21 and 1.40 times higher than that from an AG suspension and AG ethanol solution, respectively. The pharmacokinetic results indicate that the absorption of AG from AG-NE was significantly enhanced in comparison with that from the AG suspension, with a relative bioavailability of 594.3%. Moreover, the ulcer index and histological damage score of mice with indomethacin-induced intestinal lesions were significantly reduced by AG-NE pretreatment. Conclusion We conclude that the developed AG-NE not only enhanced the oral bioavailability of AG in this study but may also prove to be an effective formulation of AG for preventing gastrointestinal inflammatory disorders.

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confidence: 99%

Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide

Yen

Chen

et al. 2018

IJN

110

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“…The presence of surfactant, ie, Tween 80, was reported to induce membrane perturbation and P-glycoprotein inhibition that enhanced the permeability of sulpiride. [52][53][54] It was also suggested that Tween 80 modulates P-glycoprotein efflux by inhibition of protein kinase C activity, causing a reduction in phosphorylation of P-glycoprotein and thereby reducing the transport function of P-glycoprotein. 55 The results of our study cannot confirm this finding.…”

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confidence: 99%

Novel sulpiride-loaded solid lipid nanoparticles with enhanced intestinal permeability

Ibrahim¹,

Alomrani²,

Yassin³

2013

IJN

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Background Solid lipid nanoparticles (SLN), novel drug delivery carriers, can be utilized in enhancing both intestinal permeability and dissolution of poorly absorbed drugs. The aim of this work was to enhance the intestinal permeability of sulpiride by loading into SLN. Methods A unique ultrasonic melt-emulsification method with minimum stress conditions was used for the preparation of SLN. The mixture of the drug and the melted lipids was simply dispersed in an aqueous solution of a surfactant at a temperature that was 10°C higher than the melting points of the lipids using probe sonication, and was then simultaneously dispersed in cold water. Several formulation parameters were optimized, including the drug-to-lipid ratio, and the types of lipids and surfactants used. The produced SLN were evaluated for their particle size and shape, surface charge, entrapment efficiency, crystallinity of the drug and lipids, and the drug release profile. The rat everted sac intestine model was utilized to evaluate the change in intestinal permeability of sulpiride by loading into SLN. Results The method adopted allowed successful preparation of SLN with a monodispersed particle size of 147.8–298.8 nm. Both scanning electron microscopic and atomic force microscopic images showed uniform spherical particles and confirmed the sizes determined by the light scattering technique. Combination of triglycerides with stearic acid resulted in a marked increase in zeta potential, entrapment efficiency, and drug loading; however, the particle size was increased. The type of surfactant used was critical for particle size, charge, drug loading, and entrapment efficiency. Generally, the in vitro release profile demonstrated by all formulations showed the common biphasic mode with a varying degree of burst release. The everted sac model showed markedly enhanced sulpiride permeability in the case of the SLN-loaded formulation. The in situ results showed a very good correlation with the in vitro release data. Conclusion Incorporation of sulpiride into SLN results in enhanced intestinal permeability of sulpiride, that may in turn increase overall oral absorption of the drug. The superior attributes of the prepared SLN, specifically the high particle size uniformity and drug loading capacity, is considered novel, especially given the simplicity and modest nature of the sonication method used.

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“…Glycols like phospholipon H is a lipoid characterized by natural and hydrogenated lecithin fractions and phospholipids that would enhance the absorption by changing the intestinal membrane fluidity [13] . The excipients like alcohols and glycols, fatty alcohols, surfactants and Solutol increase the permeability by increasing the membrane fluidity and/or disrupting the membrane structure [14][15][16][17] .…”

Section: Table 3: Pharmacokinetic Parameters Of Paromomycin After IV mentioning

confidence: 99%

“…Surfactants like sodium lauryl sulphate, Tween 80 and Cremophor EL were used at ≥10% and were reported to inhibit P-gp and SLS by increasing the fluidity of intestinal membrane resulting in increase in the plasma exposure [20] . Cremophor EL was also reported to increase the permeability by disrupting the intestinal barrier [21] . Terpenes like menthol were shown to increase the permeability either by increasing the fluidity or by disruption of tight junctions of intestinal membrane [22] .…”

Section: Table 3: Pharmacokinetic Parameters Of Paromomycin After IV mentioning

confidence: 99%

Investigation of Different Formulation Approaches to Enhance Oral Bioavailability of Paromomycin

Pinjari¹,

Somani²,

Gilhotra³

2017

pharmaceutical-sciences

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Pinjari, et al.: Different Formulation Approach for ParomomycinParomomycin, an aminoglycoside antibiotic, is used to treat visceral leishmaniasis as an intramuscular injection daily for 21 days since it has limited oral bioavailability. The objective of this investigation is to improve the oral bioavailability through formulation development for increased patient compliance and convenience. Comparative pharmacokinetic studies of intravenous and oral administration of paromomycin in mice to evaluate different formulation approaches to increase oral bioavailability were carried out. Following intravenous injection of 15 mg/kg to mice, paromomycin exhibited low plasma clearance (8 ml/min/kg) with elimination half-life of 2.6 h. Following oral administration of 500 mg/kg of a suspension formulation using carboxymethylcellulose to mice, referred to as formulation 1, paromomycin showed very low or negligible oral bioavailability (%F=0.3). Different formulation approaches were made by employing a variety of FDA-approved novel excipients belonging to glycols, fatty acids, alcohols and surfactants alone and in various combinations. In vivo pharmacokinetic studies with these formulations demonstrated improved oral bioavailability of paromomycin in mice. Formulation approaches tested in the present research project were successful in improving the oral bioavailability of paromomycin from 0.3% to a maximum of 9%. Overall, the increase in paromomycin bioavailability ranged 1-30 fold with different formulations compared to carboxymethylcellulose formulation. Formulation with 10% Gelucire 44/14, 10% Solutol HS 15, 30% propylene glycol and 50% normal saline showed higher bioavailability compared to formulation 1. This research provided evidence that improved bioavailability of paromomycin can be achieved through formulation development, which eventually could result in making the most tedious and painful intramuscular therapy redundant.

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Modulation of Intestinal P-Glycoprotein Function by Cremophor EL and Other Surfactants by an In Vitro Diffusion Chamber Method Using the Isolated Rat Intestinal Membranes

Cited by 150 publications

References 17 publications

Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide

Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide

Novel sulpiride-loaded solid lipid nanoparticles with enhanced intestinal permeability

Investigation of Different Formulation Approaches to Enhance Oral Bioavailability of Paromomycin

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