Water-soluble polycations as oral drug carriers (tablets).
New bioerodible materials that are noncross-linked and water-soluble copolymers of trimethylaminoethyl methacrylate chloride (TMAEMC) and methyl methacrylate (MMA) were synthesized and then bound to anionic drugs (diclofenac Na and Na sulfathiazote) to form water-insoluble complexes. These drug-polymer complexes release the bound drugs only in ionic media. Compressed tablets were prepared from these anion-exchange resins, and their release profiles follow zero-order kinetics (n > 0.89, where n is the release exponent). The effects of various excipients (dextrose, lactose, and microcrystalline cellulose) were studied, and the polymer composition was found to influence the duration of drug release. It was also found that the release of anionic drugs from drug-PTMAEM/MMA is linear and that it is possible to "tailor-make" their release kinetics by suitably altering the copolymer composition. When a high content of a water-insoluble excipient (i.e., microcrystalline cellulose) was used to fabricate the tablets, the release kinetics deviated from linearity (n = 0.73). In general, release kinetics were well described by a dissociation/erosion mechanism. Drug loading could be increased by increasing the exchange capacity of the polymer (i.e., by increasing the content of the quaternary amine monomer).
Konar
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N
School of Pharmacy, Temple University, Philadelphia, PA 19140, USA.
Kim
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C
D002412:Cations; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D008768:Methylmethacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D000077589:Sulfathiazole; D013432:Sulfathiazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013607:Tablets
D002412:Cations; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008768:Methylmethacrylates; D013432:Sulfathiazoles; C110485:TMAEMC-methyl methacrylate copolymer; D013607:Tablets; D004008:Diclofenac; D000077589:Sulfathiazole