Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers

Christiansen, M. Skytte; Holm, René; Abrahamsson, Bertil; Jacobsen, Jette Bredahl; Kristensen, Jakob; Andersen, Jens Rikardt; Müllertz, Anette

doi:10.1016/j.ejps.2016.01.011

Cited by 29 publications

(16 citation statements)

References 45 publications

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“…The following mechanisms are implicated for the improvement of permeability: Gastric retention time—the oils in the SEDDS can decrease the gastric emptying rate [ 6 ]. Lymphatic transport—the oils in the SEDDS may enhance the lymphatic transportation and the bioavailability of highly lipophilic drugs by promoting their association with chylomicrons in the enterocytes and avoiding hepatic metabolic pathways [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Self-Emulsifying Granules and Pellets: Composition and Formation Mechanisms for Instant or Controlled Release

Nikolakakis

Partheniadis

2017

Pharmaceutics

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Many articles have been published in the last two decades demonstrating improvement in the dissolution and absorption of low solubility drugs when formulated into self-emulsifying drug delivery systems (SEDDS). Several such pharmaceutical products have appeared in the market for medium dose (Neoral® for Cyclsoprin A, Kaletra® for Lopinavir and Ritonavir), or low dose medications (Rocaltrol® for Calcitriol and Avodart® for Dutasteride). However, these are in the form of viscous liquids or semisolid presentations, characterized by the disadvantages of high production cost, stability problems and the requirement of large quantities of surfactants. Solid SEDDS (S-SEDDS), as coarse powders, granules or pellets, besides solubility improvement, can be filled easily into capsules or processed into tablets providing a handy dosage form with instant release, which can be further developed into controlled release by mixing with suitable polymers or coating with polymeric films. In this review, the materials used for the preparation of S-SEDDS, their properties and role in the formulations are detailed. Factors affecting the physical characteristics, mechanical properties of S-SEDDS as well as their in vitro release and in vivo absorption are discussed. The mechanisms involved in the formation of instant and sustained release self-emulsifying granules or pellets are elucidated. Relationships are demonstrated between the characteristics of S-SEDDS units (size, shape, mechanical properties, re-emulsification ability, drug migration and drug release) and the properties of the submicron emulsions used as massing liquids, with the aim to further elucidate the formation mechanisms. The influence of the composition of the powdered ingredients forming the granule or pellet on the properties of S-SEDDS is also examined. Examples of formulations of S-SEDDS that have been reported in the literature in the last thirteen years (2004–2017) are presented.

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Section: Introductionmentioning

confidence: 99%

Self-Emulsifying Granules and Pellets: Composition and Formation Mechanisms for Instant or Controlled Release

Nikolakakis

Partheniadis

2017

Pharmaceutics

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“…The total absorption of Cinnarizine from C-SNEDDS in the fasted and fed state was not significantly different as evidenced by the study. Also, as per C max value, it is not beneficial to administer a placebo SNEDDS with Cinnarizine tablet (Christiansen et al, 2016). But, to draw any firm conclusion, more studies with higher number of subjects are necessary.…”

Section: In Vivo Studies On Human Volunteersmentioning

confidence: 99%

“…It can be explained that the enhancement of bioavailability by SMEDDS was due to the combined mechanism of good solubilization, possible lymphatic transport and inhibition of the efflux transporter by the components, Tween 80 and Labrasol. Christiansen et al (2016) have evaluated the effect of placebo SNEDDS in Cinnarizine bioavailability and gastric emptying time following administration of a Cinnarizine tablet with placebo SNEDDS (C-SNEDDS) in human volunteers in the fasted and fed state compared to a commercial Cinnarizine tablet without SNEDDS (C-TAB). From the pharmacokinetic studies, it was observed that C-SMEDDS, which resulted in lower C max than C-TAB in the fed state.…”

Section: In Vivo Studies On Human Volunteersmentioning

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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“…. In this context, Christiansen et al 12 have shown that under fasted state conditions, the co-administration of 0.5 g of drug-free SNEDDS (sesame oil, Cremophor RH40, oleic acid, Brij and ethanol) with a CIN tablet (Sepan ® ) induced an increased extent of CIN absorption in humans compared to the administration of a CIN tablet without drug-free SNEDDS.…”

Section: Introductionmentioning

confidence: 99%

Exploring the utility of the Chasing Principle: influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension

Jørgensen

Rades

et al. 2019

Acta Pharmaceutica Sinica B

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This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol (CAR), cinnarizine (CIN) or R3040 on drug solubilization in a two-compartment in vitro lipolysis model. Correlation of drug logP or solubility in SNEDDS with drug solubilization during in vitro lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1 (1:1, w/w) and Kolliphor RH40, with ethanol at 10% (w/w) were used. SNEDDS were named F65, F55 and F20 (numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS (F0) were also analyzed. While the ranking order of drug solubilization was F65=F55=F20>F0 for CAR; F65=F55>F20>F0 for CIN and F65=F55=F20>F0 for R3040 - with higher CAR solubilization than for R3040 and CIN - the ranking of Seq of CAR, CIN and R3040 in SNEDDS was F65F20 and F65>F55>F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high Seq in SNEDDS did not reflect high drug solubilization. As CAR (logP 3.8) showed higher solubilization than CIN (logP 5.8) and R3040 (logP 10.4), a correlation between drug logP and drug solubilization was observed.

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Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers

Cited by 29 publications

References 45 publications

Self-Emulsifying Granules and Pellets: Composition and Formation Mechanisms for Instant or Controlled Release

Self-Emulsifying Granules and Pellets: Composition and Formation Mechanisms for Instant or Controlled Release

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

Exploring the utility of the Chasing Principle: influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension

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