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POLYETHYLENE OXIDES AS MATRIX FORMING AGENTS: DIRECT COMPRESSION VS. WET GRANULATION
Published: 24 April 2012 by MDPI in The 2nd Electronic Conference on Pharmaceutical Sciences session Advances in the solid state field
Abstract: Polyethylene oxides are widely used in formulation of extended release systems, especially matrix tablets. In this study we examined the influence of different types and concentration of polyethylene oxides as well as various manufacturing procedures on drug release rate. Tablets were prepared by (a) direct compression or (b) compression of granules obtained by fluid bed wet granulation. In both cases, tablets contained paracetamol as model substance, polymer and anhydrous lactose as a diluent. Polymers of different molecular weights were used: Polyox® WSR N-12K (approximate molecular weight 1 000 000) and Polyox® WSR Coagulant (approximate molecular weight 5 000 000) in concentration of 20 % and 30 %. Drug release rate was determined in the rotating paddle apparatus (phosphate buffer pH= 5,8; 50rpm; volume 900ml). Swelling behaviour of tablets (water uptake and thickness of the gel layer) was examined during eight hours. Model-dependent methods were used in evaluation of drug release and swelling behaviour of PEO tablets. Lower release rate was achieved using polyethylene oxide of higher molecular weight (Polyox® WSR Coagulant) and higher polymer content, as was expected. Both direct compression and wet granulation were efficient in prolonging drug release. Slower drug release was obtained when wet granulation was used. The slowest, zero-order drug release was achieved with Polyox® WSR Coagulant in concentration of 30 % and wet granulation as manufacturing procedure with about 53 % of released drug after 8 hours. Polymer content was optimized considering manufacturing process, drug release kinetics as well as extended release during 8 hours of study.
Keywords: fluid bed granulation, prolonged release, polyethylene oxides