Role of lipid-based excipients and their composition on the bioavailability of antiretroviral self-emulsifying formulations

Chudasama, Arpan; Patel, Vineetkumar; Nivsarkar, Manish; Vasu, Kamala K.; Shishoo, C. J.

doi:10.3109/10717544.2014.891270

Cited by 17 publications

(16 citation statements)

References 53 publications

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“…Better in vivo absorption in the presence of Tween 80 ascribed to the possible inhibition of efflux transport and increased lymphatic transport. In another research, the presence of higher concentration of Tween 80 (56.4%) and lower concentration of oil (Caprylic acid; 20%) in a SEDDS of Nevirapine resulted in better ex vivo intestinal permeability as well as better C max and AUC 0-t compared to the SEDDS containing lower Tween 80 (46.8%) and higher oil (20%), although both formulations resulted better oral bioavailability in rats than marketed suspension (Chudasama et al, 2015). From all these discussed studies, it can be concluded that the in vitro models, undoubtedly can give idea about drug absorption through the intestine, but in vivo studies are essential to find out the exact outcome of the delivery system.…”

Section: Correlation Between In Vitro Model and In Vivo Studiesmentioning

confidence: 99%

Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view

et al. 2016

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Self-emulsifying drug delivery system (SEDDS) is an isotropic mixture of lipid, surfactant and co-surfactant, which forms a fine emulsion when comes in contact of an aqueous medium with mild agitation. SEDDS is considered as a potential platform for oral delivery of hydrophobic drug in order to overcome their poor and irregular bioavailability challenges. In spite of fewer advantages like improved solubility of drug, bypassing lymphatic transport etc., SEDDS faces different controversial issues such as the use of appropriate terminology (self-microemulsifying drug delivery system; SMEDDS or self-nanoemulsifying drug delivery system; SNEDDS), presence of high amount of surfactant, correlation of in vitro model to in vivo studies, lack of human volunteer study and effect of conversion of SEDDS to final administrable dosage form on pharmacokinetic behavior of the drug. In this review, potential issues or questions on SEDDS are identified and summarized from the pharmacokinetic point of view. Primarily this review includes the conflict between the influences of droplet size, variation in correlation between in vitro lipolysis or ex-vivo intestinal permeation and pharmacokinetic parameters, variation in in vivo results of solid and liquid SEDDS, and potential challenges or limitation of pharmacokinetic studies on human volunteers with orally administered SEDDS. In the past decades, hundreds of in vivo studies on SEDDS have been published. In the present study, only the relevant article on in vivo pharmacokinetic studies with orally administered SEDDS published in past 5-6 years are analyzed for an up to date compilation. KeywordsPoor bioavailability, self-nanoemulsifying delivery system, self-microemulsifying delivery system, in vitro lipolysis, pharmacokinetic of SEDDS History

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Section: Correlation Between In Vitro Model and In Vivo Studiesmentioning

confidence: 99%

Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view

et al. 2016

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“…Their purpose is mainly to dissolve lipophilic drugs into liquid formulations or to promote consistent, uniform dispersion into gastrointestinal fluid after oral administration. By including TGs or their derivatives in oral formulations, the intestinal absorption of poorly water-soluble drugs can be improved and the degree of interindividual variation can be reduced. − From the oral administration of such medicines, the range of intake of TGs may be a few grams. The dietary intake of fat (TGs) could be more than 50 g per day; however, this amount strongly depends on the individual.…”

Section: Discussionmentioning

confidence: 99%

Impact of Dietary Intake of Medium-Chain Triacylglycerides on the Intestinal Absorption of Poorly Permeable Compounds

et al. 2019

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The present study sought to demonstrate the effect of dietary intake of medium-chain triacylglycerides (MCTs) on the intestinal absorption of a poorly permeable compound of intermediate molecular weight (FITC-dextran 4000 ). As a model of MCTs, C 8 −C 12 fatty acid triacylglyceride (COCONAD ML) was mainly used, and the dose strength of each triglyceride was set with consideration of the dietary ingestion dose (12.5 mg/rat). When FD-4 with MCTs dispersed in fasted state simulated intestinal fluid containing surfactants was administered into the rat jejunum, the intestinal absorption of FD-4 was significantly higher than when administered with a similar solution with or without corn oil (long-chain triglycerides). The effects of pretreatment by MCT lipolysis, inhibition of endogenous lipases, and different dose timings of MCTs and FD-4 on the intestinal absorption of FD-4 indicated that medium-chain fatty acids, such as caprylic acid and capric acid, released from MCTs by lipolysis in the small intestine significantly enhanced the intestinal absorption of FD-4, but the effect was transient. In addition, a similar effect was observed when MCTs were dispersed in soymilk, although large interindividual variation was detected. These findings suggested that dietary intake of MCTs might affect the intestinal absorption of poorly permeable compounds.

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“…40 Different ratios of surfactants were used to stabilize droplet surfaces with enhanced RAV incorporation capacity. RAV was loaded in F2 (5% Epikuron) at concentrations up to 6 mg/mL, with a significant increase in mean diameter from 215 nm to 247 nm (P,0.05).…”

Section: -21mentioning

confidence: 99%

Ravuconazole self-emulsifying delivery system: in vitro activity against <em>Trypanosoma cruzi</em> amastigotes and in vivo toxicity

Spósito

Mazzeti

Faria

et al. 2017

IJN

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Self-emulsifying drug delivery systems (SEDDSs) are lipid-based anhydrous formulations composed of an isotropic mixture of oil, surfactant, and cosurfactants usually presented in gelatin capsules. Ravuconazole (Biopharmaceutics Classification System [BCS] Class II) is a poorly water-soluble drug, and a SEDDS type IIIA was designed to deliver it in a predissolved state, improving dissolution in gastrointestinal fluids. After emulsification, the droplets had mean hydrodynamic diameters <250 nm, zeta potential values in the range of −45 mV to −57 mV, and showed no signs of ravuconazole precipitation. Asymmetric flow field-flow fractionation with dynamic and multiangle laser light scattering was used to characterize these formulations in terms of size distribution and homogeneity. The fractograms obtained at 37°C showed a polydisperse profile for all blank and ravuconazole–SEDDS formulations but no large aggregates. SEDDS increased ravuconazole in vitro dissolution extent and rate (20%) compared to free drug (3%) in 6 h. The in vivo toxicity of blank SEDDS comprising Labrasol ® surfactant in different concentrations and preliminary safety tests in repeated-dose oral administration (20 days) showed a dose-dependent Labrasol toxicity in healthy mice. Ravuconazole–SEDDS at low surfactant content (10%, v/v) in Trypanosoma cruzi -infected mice was safe during the 20-day treatment. The anti- T. cruzi activity of free ravuconazole, ravuconazole–SEDDS and each excipient were evaluated in vitro at equivalent ravuconazole concentrations needed to inhibit 50% or 90% (IC 50 and IC 90 ), respectively of the intracellular amastigote form of the parasite in a cardiomyocyte cell line. The results showed a clear improvement of the ravuconazole anti- T. cruzi activity when associated with SEDDS. Based on our results, the repurposing of ravuconazole in SEDDS dosage form is a strategy that deserves further in vivo investigation in preclinical studies for the treatment of human T. cruzi infections.

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Role of lipid-based excipients and their composition on the bioavailability of antiretroviral self-emulsifying formulations

Cited by 17 publications

References 53 publications

Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view

Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view

Impact of Dietary Intake of Medium-Chain Triacylglycerides on the Intestinal Absorption of Poorly Permeable Compounds

Ravuconazole self-emulsifying delivery system: in vitro activity against <em>Trypanosoma cruzi</em> amastigotes and in vivo toxicity

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