Development of a supersaturable SEDDS (S‐SEDDS) formulation of paclitaxel with improved oral bioavailability

Gao, Ping; Rush, Bob D.; Pfund, William P.; Huang, Tian-Sen; Bauer, Juliane M.; Morozowich, W.; Kuo, Ming‐Shang; Hageman, Michael J.

doi:10.1002/jps.10511

Cited by 311 publications

(222 citation statements)

References 27 publications

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“…Other P-glycoprotein blockers that could also serve as CYP 450 inhibitors also boosted the oral absorption of paclitaxel Bardelmeijer et al, 2004;Choi & Li, 2005;Kim et al, 2004;. Formulations that do not contain Cremophor EL, that could lower the in vivo toxicity and increase solubilization of paclitaxel, were shown to deliver paclitaxel efficiently via oral administration especially when P-glycoprotein inhibitors were given simultaneously Gao et al, 2003;Yang et al, 2004;Woo et al, 2003;Choi et al, 2004aChoi et al, , 2004bPeltier et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Development, Optimization and Absorption Mechanism of DHP107, Oral Paclitaxel Formulation for Single-Agent Anticancer Therapy

Lee¹,

Hong²,

Jang³

et al. 2012

New Advances in the Basic and Clinical Gastroenterology

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Section: Introductionmentioning

confidence: 99%

Development, Optimization and Absorption Mechanism of DHP107, Oral Paclitaxel Formulation for Single-Agent Anticancer Therapy

Lee¹,

Hong²,

Jang³

et al. 2012

New Advances in the Basic and Clinical Gastroenterology

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“…Selection of a suitable self-emulsifying formulation depends upon the assessment of drug solubility in various components, the area of the self-emulsifying region obtained in the phase diagram, and the droplet size distribution of the resultant emulsion following self-emulsification (9). SEDDS formulation offers the opportunity to deliver lipophilic drugs to the gastrointestinal tract in a dissolved state, avoiding the dissolution step (which can limit the absorption rate of BCS class II and IV drugs), reduction in inter-and intra-subject variability, reduction of food effect, ease of manufacturing and scale-up, ability to deliver peptides that are prone to enzymatic hydrolysis in GIT and no influence of lipid digestion process (10)(11)(12).…”

mentioning

confidence: 99%

Formulation development of an albendazole self-emulsifying drug delivery system (SEDDS) with enhanced systemic exposure / Razvoj samoemulzifirajućeg sustava za isporuku albendazola (SEDDS) s pojačanom sistemskom apsorpcijom

Meena¹,

Sharma

Kandaswamy

et al. 2012

Acta Pharmaceutica

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Most of the new chemical entities (NCEs) are poorly water-soluble and pose a challenge to developing an optimum solid oral dosage form. Oral route has been the major route of drug delivery for the treatment of various diseases. Delivery of poorly water--soluble molecules by oral route is difficult because approximately 40 % of drug compounds are limited to low aqueous solubility, which leads to restricted oral bioavailability, high intra-and inter-subject variability and lack of dose proportionality (1).To increase the oral bioavailability of poorly water-soluble compounds and eliminate the discussed drawbacks, various other formulation strategies have been adopted, including the use of cyclodextrins, nanoparticles, solid dispersions and permeation en- The aim of the study was to develop and evaluate a self--emulsifying drug delivery system (SEDDS) formulation to improve solubility and dissolution and to enhance systemic exposure of a BCS class II anthelmetic drug, albendazole (ABZ). In the present study, solubility of ABZ was determined in various oils, surfactants and co-surfactants to identify the microemulsion components. Pseudoternary phase diagrams were plotted to identify the microemulsification existence area. SEDDS formulation of ABZ was prepared using oil (Labrafac Lipopfile WL1349) and a surfactant/co-surfactant (Tween 80/PEG 400) mixture and was characterized by appropriate studies, viz., microemulsifying properties, droplet size measurement, in vitro dissolution, etc. Finally, PK of the ABZ SEDDS formulation was performed on rats in parallel with suspension formulation. It was concluded that the SEDDS formulation approach can be used to improve the dissolution and systemic exposure of poorly water-soluble drugs such as ABZ.

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“…2) Un tel profil a été décrit auparavant dans la littérature [24,36]. La demi-vie d'élimination du principe actif est de 4,5 h et le TRM de 2,6 h. Ces deux résultats concordent aussi avec des valeurs antérieurement décrites [16,22,23]. Quand le médicament commercial est administré par voie orale, les niveaux plasmatiques du paclitaxel sont inférieurs à la limite de détection de la technique analytique utilisée.…”

Section: Discussion Et Conclusionunclassified

“…Malheureusement, au moins dans certains cas, l'index thérapeutique de ces produits est plus faible que celui du paclitaxel [19,20]. Pour résoudre ce problème tout en promouvant la biodisponibilité orale du paclitaxel, le recours à plusieurs systèmes de délivrance de médicaments a été envisagé : micelles [21], systèmes autoemulsionables [22,23], nanoémulsions [24] et nanocapsules lipidiques [16]. De tels systèmes permettent, en général, l'association, à la formulation, d'inhibiteurs de la P-gp et du cytochrome P450, tels que la cyclosporine A [22] ou des flavonoïdes [25].…”

Section: Introductionunclassified

Nanoparticules mucopénétrantes : véhicules pour l’administration orale du paclitaxel

Zabaleta

Calleja

Espuelas

et al. 2013

Annales Pharmaceutiques Françaises

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RésuméLe paclitaxel est un agent anticancéreux utilisé en solution pour perfusion intraveineuse dans le traitement de différents types de cancer. Dans les dernières années, de nombreuses stratégies ont été proposées pour le développement d'une formulation orale de cet anticancéreux. Toutefois, la faible solubilité aqueuse du paclitaxel et le fait qu'il soit un substrat de la pglycoprotéine intestinale et du complexe enzymatique cytochrome P450 compliquent énormément le problème. Dans ce travail, des nanoparticules pégylées avec des propriétés mucopénétrantes ont été développées pour acheminer le paclitaxel jusqu'à la surface des entérocytes. Des particules présentant une taille moyenne d'environ 180 nm et un contenu en paclitaxel proche de 15% ont été préparées. Une étude pharmacocinétique chez la souris a montré que les nanoparticules permettent d'obtenir des niveaux plasmatiques efficaces et soutenus du paclitaxel pendant 3 jours. Au total, la biodisponibilité relative orale du paclitaxel, encapsulé dans des nanoparticules pégylées avec du PEG 2000, est proche du 85%. Chez la souris, sur un modèle de tumeur sous-cutanée, ces mêmes nanoparticules administrées par voie orale, une fois tous les trois jours, ont permis d'obtenir une efficacité similaire à celle offerte par le médicament commercialisé administré par voie intraveineuse journellement pendant 9 jours. L'ensemble des résultats tend à démontrer que les nanoparticules développées sont capables de traverser la couche du mucus intestinal et d'atteindre, ainsi, la surface des entérocytes. Les molécules de PEG favorisent l'adhésion des particules à la surface des cellules, évitent la métabolisation du paclitaxel et accroissent son absorption. Mots-clés : nanoparticules, paclitaxel, orale, poly (éthylène glycol), libération contrôlée SummaryPaclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with muco-penetrating properties in order to conduct paclitaxel till the surface of the enterocyte. These nanoparticles displayed a size of about 180 nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol administered intravenously every day during 9 days. 3All of these results suggested ...

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Development of a supersaturable SEDDS (S‐SEDDS) formulation of paclitaxel with improved oral bioavailability

Cited by 311 publications

References 27 publications

Development, Optimization and Absorption Mechanism of DHP107, Oral Paclitaxel Formulation for Single-Agent Anticancer Therapy

Development, Optimization and Absorption Mechanism of DHP107, Oral Paclitaxel Formulation for Single-Agent Anticancer Therapy

Formulation development of an albendazole self-emulsifying drug delivery system (SEDDS) with enhanced systemic exposure / Razvoj samoemulzifirajućeg sustava za isporuku albendazola (SEDDS) s pojačanom sistemskom apsorpcijom

Nanoparticules mucopénétrantes : véhicules pour l’administration orale du paclitaxel

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