A pH-dependent colon targeted oral drug delivery system using methacrylic acid copolymers. I. Manipulation Of drug release using Eudragit L100-55 and Eudragit S100 combinations.
Lactose-based placebo tablets were coated using various combinations of two methacrylic acid copolymers, Eudragit L100-55 and Eudragit S100, by spraying from aqueous systems. The Eudragit L100-55-Eudragit S100 combinations (w/w) studied were 1:0, 4:1, 3:2, 1:1, 2:3, 1:4, 1:5 and 0:1. The coated tablets were tested in vitro for their suitability for pH dependent colon targeted oral drug delivery. The same coating formulations were then applied on tablets containing mesalazine as a model drug and evaluated for in vitro dissolution rates under various conditions. The disintegration data obtained from the placebo tablets demonstrate that disintegration rate of the studied tablets is dependent on: (i) the polymer combination used to coat the tablets, (ii) pH of the disintegration media, and (iii) the coating level of the tablets. Dissolution studies performed on the mesalazine tablets further confirmed that the release profiles of the drug could be manipulated by changing the Eudragit L100-55 and Eudragit S100 ratios within the pH range of 5.5 to 7.0 in which the individual polymers are soluble respectively, and a coating formulation consisting of a combination of the two copolymers can overcome the issue of high gastrointestinal (GI) pH variability among individuals. The results also demonstrated that a combination of Eudragit L100-55 and Eudragit S100 can be successfully used from aqueous system to coat tablets for colon targeted delivery of drugs and the formulation can be adjusted to deliver drug at any other desirable site of the intestinal region of the GI tract on the basis of pH-variability. For colon targeted delivery of drugs the proposed combination system is superior to tablets coated with either Eudragit L100-55 or Eudragit S100 alone.
Drugs Development Department, Research Institute, PLIVA d.d., Prilaz baruna Filipovića 25, 10 000 Zagreb, Croatia. krunoslav.kovacevic@zg.tel.hr
M Z
MZ
Khan
Z
Z
Prebeg
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N
Kurjaković
D000180:Acrylic Resins; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005079:Excipients; D005782:Gels; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008689:Methacrylates / Q000737:chemistry*; D011109:Polymethacrylic Acids; D012995:Solubility
D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D008689:Methacrylates; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer