title: Tablets of pre-liposomes govern in situ formation of liposomes: concept and potential of the novel drug delivery system.
abstract: The purpose of this study was to develop a novel drug delivery system for challenging drugs with potential for scale-up manufacturing and controlled release of incorporated drug. Pre-liposomes powder containing metronidazole, lecithin and mannitol, prepared by spray-drying, was mixed with different tableting excipients (microcrystalline cellulose, lactose monohydrate, mannitol, dibasic calcium phosphate, pregelatinized starch, pectin or chitosan) and compressed into tablets. The delivery system was characterized with respect to (i) dry powder characteristics, (ii) mechanical tablet properties and drug release, and (iii) liposomal characteristics. The pre-liposomes powder was free-flowing, and tablets of similarly high qualities as tablets made of physical mixtures were prepared with all excipients. Liposomes were formed in situ upon tablet disintegration, dissolution or erosion depending on the type of tablet excipient used. The liposomal characteristics and drug release were found to depend on the tablet excipient. The new delivery system offers a unique synergy between the ability of liposomes to encapsulate and protect drugs and increased stability provided by compressed formulations. It can be adjusted for drug administration via various routes, e.g. oral, buccal and vaginal.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia. Electronic address: zvanic@pharma.hr.
authors.forename: Željka
authors.initials: Ž
authors.lastname: Vanić
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Slovenia. Electronic address: odon.planinsek@ffa.uni-lj.si.
authors.forename: Odon
authors.initials: O
authors.lastname: Planinšek
authors.affiliation: Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, Norway. Electronic address: natasa.skalko-basnet@uit.no.
authors.forename: Nataša
authors.initials: N
authors.lastname: Škalko-Basnet
authors.affiliation: Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, Norway. Electronic address: ingunn.tho@farmasi.uio.no.
authors.forename: Ingunn
authors.initials: I
authors.lastname: Tho
mesh_terms: D002152:Calorimetry, Differential Scanning; D016503:Drug Delivery Systems; D008081:Liposomes; D008855:Microscopy, Electron, Scanning; D011208:Powders; D013607:Tablets
chemical_list: D008081:Liposomes; D011208:Powders; D013607:Tablets
keywords: Controlled release; Lipid-based tablets; Metronidazole; Nanocarrier-in-tablet; Soybean lecithin; Spray-dried powder