Drug release from hydrophilic matrices. 2. A mathematical model based on the polymer disentanglement concentration and the diffusion layer.
A comprehensive model is developed to describe the swelling/dissolution behaviors and drug release from hydrophilic matrices. The major thrust of this model is to employ an important physical property of the polymer, the polymer disentanglement concentration, rho p,dis, the polymer concentration below which polymer chains detach off the gelled matrix. For (hydroxypropyl)methylcellulose (HPMC) in water, we estimate that rho p,dis scales with HPMC molecular weight, M, as rho p,dis varies M-0.8. Further, matrix dissolution is considered similar to the dissolution of an object immersed in a fluid. As a result, a diffusion layer separating the matrix from the bulk solution is incorporated into the transport regime. An anisotropic expansion model is also introduced to account for the anisotropic expansion of the matrix where surface area in the radial direction dominates over the axial surface area. The model predicts that the overall tablet size and the characteristic swelling time correlate with rho p,dis qualitatively. Two scaling laws are established for fractional polymer (mp(t)/mp(infinity)) and drug (md(t)/md(infinity)) released as mp(t)/mp(infinity) varies M-1.05 and md(t)/md(infinity) varies M-0.24, consistent with the limiting polymer molecular weight effect on drug release. Model predictions for polymer and drug release agree well with observations, within 15% error. Evolution of water concentration profiles and the detailed structure of a swollen matrix are discussed.
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Drug Delivery R&D, Upjohn Company, Kalamazoo, MI 49001, USA.
Nixon
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Patel
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Tong
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D001569:Benzodiazepines / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008433:Mathematics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D008970:Molecular Weight
D003692:Delayed-Action Preparations; D001569:Benzodiazepines; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C074080:adinazolam mesylate