Duodenum-triggered delivery of pravastatin sodium: II. Design, appraisal and pharmacokinetic assessments of enteric surface-decorated nanocubosomal dispersions

Autor:	Mina Ibrahim Tadros, Mohamed A. El-Nabarawi, Saadia A. Tayel, Wessam H. Abd-Elsalam
Rok vydání:	2016
Předmět:	Male Materials science Duodenum Polymers Surface Properties Administration Oral Biological Availability Pharmaceutical Science Poloxamer 02 engineering and technology 030226 pharmacology & pharmacy Intestinal absorption 03 medical and health sciences First pass effect Drug Delivery Systems 0302 clinical medicine Pharmacokinetics Zeta potential Animals Particle Size Rats Wistar Pravastatin Aqueous solution Chromatography General Medicine 021001 nanoscience & nanotechnology Rats Bioavailability Pravastatin Sodium Intestinal Absorption Delayed-Action Preparations cardiovascular system Nanoparticles 0210 nano-technology
Zdroj:	Drug Delivery. 23:3266-3278
ISSN:	1521-0464 1071-7544
DOI:	10.3109/10717544.2016.1172367
Popis:	Pravastatin sodium (PVS) is a freely water-soluble HMG-CoA inhibitor that suffers from instability at gastric pH, extensive first pass metabolism, short elimination half-life (1-3 h) and low oral bioavailability (18%).To overpower these drawbacks and to maximize drug absorption at its main site of absorption at the duodenum, enteric surface-coated PVS-loaded nanocubosomal dispersions were presented.Glyceryl monooleate (GMO)-based dispersions were developed by the fragmentation or the liquid precursor methods using Pluronic® F127 or Cremophor® EL as surfactants. As a challenging enteric-coating approach, the promising dispersions were surface-coated via lyophilization with Eudragit® L100-55; a duodenum-targeting polymer. The drug content, particle size, zeta potential, morphology and release studies of PVS-loaded dispersions were evaluated before and after surface-coating. Compared to an aqueous PVS solution, the pharmacokinetics of the best achieved system (E-F8) was evaluated (UPLC-MS/MS) in rats.The enteric surface-coated nanocubosomal dispersions were more or less spherical in shape and showed high drug-loading, negative zeta potential values and fine-tuned biphasic drug-release patterns characterized by retarded (2 h) and sustained (10 h) phases in pH 1.2 and pH 6.8, respectively. E-F8 system showed significantly (p 0.05) higher oral bioavailability, delayed TThe duodenum-triggering potential and the controlled-release characteristics of the best achieved system for smart PVS delivery were revealed.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d0406be646563839f4f7dbc82162b9e8 https://doi.org/10.3109/10717544.2016.1172367 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.