title: Duodenum-triggered delivery of pravastatin sodium via enteric surface-coated nanovesicular spanlastic dispersions: development, characterization and pharmacokinetic assessments.
abstract: Pravastatin sodium (PVS) is a hydrophilic HMG-CoA reductase inhibitor that is mainly absorbed from duodenum. PVS has a short elimination half-life (1-3 h), suffers from instability at gastric pH, extensive hepatic first-pass metabolism and low absolute bioavailability (18%). The current work aimed to develop enteric surface-coated spanlastic dispersions as controlled-release duodenum-triggered systems able to surmount PVS drawbacks. PVS-loaded spanlastic dispersions were prepared by ethanol-injection method using span(®) 60. Tween(®) 60 and Tween(®) 80 were explored as edge activators. As a novel approach, the fine spanlastic dispersions were surface-coated with an enteric-polymer (Eudragit(®) L100-55) via freeze-drying. The systems were evaluated, before and after enteric-coating, for particle size, zeta potential, PVS entrapment efficiency (EE%), morphology and PVS release studies. PVS pharmacokinetics from the best achieved system and an aqueous solution were estimated in rats by UPLC-MS/MS. The best achieved enteric surface-coated spanlastic dispersion (E-S6) displayed spherical nanosized vesicles (647.60 nm) possessing negative zeta potential (-6.93 mV), promising EE% (63.22%) and a biphasic drug-release pattern characterized by a retarded-release phase (0.1 N HCl, 2 h) and a controlled-release phase (pH 6.8, 10 h). The higher Cmax, delayed Tmax, prolonged MRT(0-∞), longer elimination t50% and enhanced oral bioavailability unravel E-S6 potential for oral PVS delivery.
authors: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, 11562 Cairo, Egypt.
authors: Saadia Ahmed
authors: SA
authors: Tayel
authors: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, 11562 Cairo, Egypt.
authors: Mohamed Ahmed
authors: MA
authors: El-Nabarawi
authors: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, 11562 Cairo, Egypt. Electronic address: mina_ebrahim@yahoo.com.
authors: Mina Ibrahim
authors: MI
authors: Tadros
authors: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, 11562 Cairo, Egypt.
authors: Wessam Hamdy
authors: WH
authors: Abd-Elsalam
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004386:Duodenum / Q000737:chemistry*; D008297:Male; D011109:Polymethacrylic Acids / Q000737:chemistry*; D017035:Pravastatin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D053719:Tandem Mass Spectrometry
chemical_list: D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D017035:Pravastatin
keywords: Duodenum-triggering; Enteric surface-coating; Ethanol injection method; Pravastatin sodium; Spanlastic dispersions; UPLC–MS/MS