Blends of enteric and GIT-insoluble polymers used for film coating: physicochemical characterization and drug release patterns.
THE OBJECTIVES OF THIS STUDY WERE: (i). to use blends of gastrointestinal tract (GIT)-insoluble and enteric polymers (ethyl cellulose and Eudragit L) as coating materials for multiparticulate controlled release dosage forms; (ii). to investigate the effects of the polymer blend ratio and coating level on the resulting drug release patterns; and (iii). to explain the observed phenomena based on the physicochemical properties of the systems. Propranolol HCl-loaded pellets were coated in a fluidized bed coater with organic polymer solutions; thin, drug-containing and drug-free, polymeric films were prepared using a casting knife. In vitro drug release, water uptake and dry weight loss studies were performed in 0.1 M HCl and phosphate buffer pH 7.4, respectively. The apparent drug diffusion coefficients within the polymeric systems were determined using different experimental and theoretical techniques (side-by-side diffusion cells, in vitro drug release from thin films; exact and approximate solutions of Fick's second law of diffusion). A broad range of drug release patterns from coated pellets could be achieved by varying the GIT-insoluble:enteric polymer blend ratio. With increasing relative amounts of Eudragit L, the release rates in both media significantly increased. The increase at low pH could be attributed to an increase in water uptake, as observed with thin films. Interestingly, only partial Eudragit L leaching occurred in phosphate buffer pH 7.4 even at high enteric polymer contents, indicating that the GIT-insoluble polymer effectively hindered the dissolution of the entrapped Eudragit L. At high pH, both polymer leaching and polymer swelling contributed to the control of drug release. The determined apparent drug diffusion coefficients take the two effects adequately into account.
College of Pharmacy, Freie Universität Berlin, Kelchstr 31, 12169 Berlin, Germany.
F
F
Lecomte
J
J
Siepmann
M
M
Walther
R J
RJ
MacRae
R
R
Bodmeier
D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003692:Delayed-Action Preparations; D004064:Digestive System / Q000378:metabolism; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics*; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013608:Tablets, Enteric-Coated / Q000737:chemistry* / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D011108:Polymers; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; C038300:methylmethacrylate-methacrylic acid copolymer; C013517:ethyl cellulose; D002482:Cellulose