title: Sucrose stearate-enriched lipid matrix tablets of etodolac: modulation of drug release, diffusional modeling and structure elucidation studies.
abstract: Etodolac is a non-steroidal anti-inflammatory drug having an elimination half-life of 7 h; oral doses are given every 6-8 h. The aim of current work was the development of controlled-release etodolac lipid matrix tablets. The variables influencing design of these tablets (L1-L28) by the hot fusion method were investigated including; (1) lipid type (stearic acid, cetyl alcohol, cetostearyl alcohol, Imwitor® 900K, Precirol® ATO 5 and Compritol® ATO 888), (2) drug/lipid ratio (1:0.25 and 1:0.50, respectively), (3) filler type (lactose, Avicel® PH101 and their physical mixtures; 2:1, 1:1, and 1:2, respectively), (4) surfactant's HLB (5 and 11), and (5) drug/surfactant ratio (20:1 and 10:1, respectively). Statistical analysis and kinetic modeling of drug release data were evaluated. The inner matrix of the tablet was visualized via scanning electron microscopy (SEM). An inverse correlation was observed between the drug/lipid ratio and the drug release rate. Precirol®- and Compritol®-containing formulae showed more retarded drug release rates. Lactose/Avicel® physical mixture (1:1) was considered as a filler of choice where it minimized the burst effect observed with Avicel®-free formulae. The higher surfactant's HLB, the higher drug release rate. The similarity factor (f(2)) between the drug release profiles revealed similarity within the investigated drug/surfactant ratios. Sucrose stearate D1805®-based matrix (L21) succeeded in delivering more than 90% of etodolac over 12 h, following anomalous (non-Fickian) controlled-release kinetics. SEM micrographs confirmed pore formation, within the latter matrix, upon contact with dissolution medium.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, 11562, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abd-Elbary
authors.forename: Mina Ibrahim
authors.initials: MI
authors.lastname: Tadros
authors.forename: Ahmed Adel
authors.initials: AA
authors.lastname: Alaa-Eldin
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers; D017308:Etodolac / Q000737:chemistry*; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D015233:Models, Statistical; D015394:Molecular Structure; D016062:Porosity; D033362:Powder Diffraction; D012995:Solubility; D013395:Sucrose / Q000031:analogs & derivatives* / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D013501:Surface-Active Agents; D013607:Tablets; C018153:sucrose monostearate; D017308:Etodolac; D013395:Sucrose