title: A quality by design (QbD) study on enoxaparin sodium loaded polymeric microspheres for colon-specific delivery.
abstract: The aim of this study was to apply quality by design (QbD) for pharmaceutical development of enoxaparin sodium microspheres for colon-specific delivery. The Process Parameters (CPPs) and Critical Quality Attributes (CQAs) were identified. A central composite experimental design was used in order to develop the design space of microspheres for colon-specific delivery that have the desired Quality Target Product Profile (QTPP). The CPPs studied were Eudragit® FS-30D/Eudragit® RS-PO ratio, poly(vinyl alcohol) (PVA) concentration and sodium chloride (NaCl) concentration. The encapsulation efficiency increased with NaCl concentration increase, the percentages of enoxaparin sodium reaching 94% for some formulations. Increasing the ratio Eudragit® FS-30D/Eudragit® RS-PO ensured a relatively complete release of enoxaparin sodium in the environment simulating the colonic pH. Based on these results, the optimum conditions were decided and the optimum formulation was prepared. The results obtained for the latter in terms of in vitro enoxaparin sodium release were good, the microparticles releasing only 9.42% enoxaparin sodium in acidic environment and 15.16% in the medium which simulated duodenal pH, but allowing the release of up to 89.24% in the medium which simulated colonic pH. The in vitro release profile of enoxaparin sodium was close to the ideal one, therefore the system was successfully designed using QbD approach.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu", 41 Victor Babeș street, 400012 Cluj-Napoca, Romania. Electronic address: dudas.dana@umfcluj.ro.
authors.forename: Dana
authors.initials: D
authors.lastname: Hales
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu", 41 Victor Babeș street, 400012 Cluj-Napoca, Romania. Electronic address: laurian.vlase@umfcluj.ro.
authors.forename: Laurian
authors.initials: L
authors.lastname: Vlase
authors.affiliation: Electron Microscopy Center, Babeș-Bolyai University, 5-7 Clinicilor street, 400006 Cluj-Napoca, Romania. Electronic address: porav_sebastian@yahoo.com.
authors.forename: Sebastian Alin
authors.initials: SA
authors.lastname: Porav
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hațieganu", 12 Ion Creangă street, 400010 Cluj-Napoca, Romania. Electronic address: abota@umfcluj.ro.
authors.forename: Andreea
authors.initials: A
authors.lastname: Bodoki
authors.affiliation: Electron Microscopy Center, Babeș-Bolyai University, 5-7 Clinicilor street, 400006 Cluj-Napoca, Romania. Electronic address: lbarbu@hasdeu.ubbcluj.ro.
authors.forename: Lucian
authors.initials: L
authors.lastname: Barbu-Tudoran
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu", 41 Victor Babeș street, 400012 Cluj-Napoca, Romania. Electronic address: machim@umfcluj.ro.
authors.forename: Marcela
authors.initials: M
authors.lastname: Achim
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu", 41 Victor Babeș street, 400012 Cluj-Napoca, Romania. Electronic address: tomutaioan@umfcluj.ro.
authors.forename: Ioan
authors.initials: I
authors.lastname: Tomuță
mesh_terms: D000925:Anticoagulants / Q000737:chemistry*; D003106:Colon; D016503:Drug Delivery Systems; D015195:Drug Design; D065546:Drug Liberation; D017984:Enoxaparin / Q000737:chemistry*; D008863:Microspheres; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D012965:Sodium Chloride; D011142:Polyvinyl Alcohol
keywords: Colon-specific delivery; Enoxaparin sodium (PubChem CID: 772); Eudragit® FS; Eudragit® FS (PubChem CID: 161546); Eudragit® RS; Eudragit® RS (PubChem CID: 104931); Microspheres; Poly(vinyl alcohol) (PubChem CID: 11199); Quality by design; Sodium chloride; Sodium chloride (PubChem CID: 5234)