Sucrose Stearate-Enriched Lipid Matrix Tablets of Etodolac: Modulation of Drug Release, Diffusional Modeling and Structu
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Research Article Sucrose Stearate-Enriched Lipid Matrix Tablets of Etodolac: Modulation of Drug Release, Diffusional Modeling and Structure Elucidation Studies Ahmed Abd-Elbary,1 Mina Ibrahim Tadros,1,3 and Ahmed Adel Alaa-Eldin2
Received 8 November 2012; accepted 28 February 2013; published online 10 April 2013 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 (f2) 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. KEY WORDS: anti-inflammatory; controlled release; etodolac; hot fusion method; lipid matrix tablets; Precirol® ATO 5; sucrose stearate; surfactant; sustained release.
INTRODUCTION Lipid matrix dosage forms are commonly employed to load drugs into inert lipophilic matrices. Many types of these matrices were recently investigated to obtain effective sustained-release drug systems, including solid lipid nanoparticles (1), extruded solid lipid matrices (2), nanostructured lipid carriers (3), liquid crystalline nanoparticles (4), lipid microspheres (5), melt-extruded helical waxy matrices (6), and lipid matrix tablets (7). The solid dispersion coating technique using waxy-retarded materials is commonly adopted to control the rate of drug release. In these systems, the active ingredient is uniformly distributed throughout the matrix and is released at a controlled rate through the pores formed within the matrix. Consequently, there is no danger of drug dumping that might be observed with accidental rupture of the membrane of other sustained-release coated systems (8). A
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