A designer's polymer as an oral drug carrier (tablet) with pseudo-zero-order release kinetics.
A new synthetic polymeric material has been investigated as an oral controlled-release system. The water soluble polymer consists of a non-cross-linked, ionic polymer possessing sulfonate functional groups: poly(sulfopropyl methacrylate potassium-co- methyl methacrylate) (PSPMK/MMA). Drug-resin complexes were obtained by preparing an aqueous solution of the polymer to which propranolol HCl as a model drug was added. Using either dextrose or microcrystalline cellulose as a tablet binder did not cause any problems in fabricating a compact drug-resinate tablet. The release of propranolol HCl from drug-resinate tablets (2.5 mm x 9.0 mm, 10% dextrose) was pseudo-zero-order kinetics from the beginning to the end for over 21 h. This was due to the greater contribution of drug release from the edge of the tablets. However, zero-order release tablets were obtained by increasing the radius to thickness ratio of the tablet to greater than 3.13. A mathematical model describing release kinetics from drug-resinate tablets predicted the effects of drug loading and the physical dimensions of the tablets by a heterogeneous dissociation/erosion-controlled mechanism. As the content of dextrose in the tablets increased, the dissociation/erosion rate constant (K0) increased due to the greater influx of water into the tablets along with counterions. As expected, the release rate was decreased as the stirring rate decreased from 100 to 50 rpm, resulting in the dissociation/erosion rate constant of 2.62-2.04 mg/cm2h, respectively. Therefore, this system has been proven to release drugs independent of the pH of simulated gastric/intestinal fluids (1.2 and 7.5) as well as the compression force of the tablet, which ranged from 1500 to 4400 lbs.
School of Pharmacy, Temple University, Philadelphia, PA 19140, USA.
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YN
Nujoma
C J
CJ
Kim
D002482:Cellulose; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D015195:Drug Design; D005947:Glucose; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000737:chemistry*; D008962:Models, Theoretical; D011108:Polymers / Q000737:chemistry*; D011312:Pressure; D011433:Propranolol / Q000737:chemistry*; D013607:Tablets / Q000737:chemistry*
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008689:Methacrylates; D011108:Polymers; D013607:Tablets; C104024:poly(sulfopropyl methacrylate potassium-co-methyl methacrylate); D002482:Cellulose; D011433:Propranolol; D005947:Glucose