Diffusion coefficients of polymer chains in the diffusion layer adjacent to a swollen hydrophilic matrix.

A semiempirical formula was developed for the diffusion coefficient, Dp, of polymer within the diffusion layer adjacent to a matrix undergoing swelling and dissolution. This formula of Dp was a key element in a comprehensive mathematical model that described the swelling and dissolution of polymer and the release of drug. For hydroxypropyl methylcellulose (HPMC), Dp can be related to molecular weight (M) and concentration (Cp) of HPMC as Dp approximately 7.24 x 10(-5) M-0.6 [1+ 700(M/ 96000)0.7Cp/8]-2. Consistent with literature results, this formula yields Dp infinity M-0.64 under a dilute condition and Dp infinity Cp-7/4M-2 under a semidilute condition. Accordingly, the average Dp within the diffusion layer, <Dp> was determined as <Dp> infinity M-0.53, suggesting that the average mobility of HPMC within the diffusion layer decreases with M. This scaling law, combined with the relationship of Cp.dis infinity M-0.8, led to an important scaling law for matrix dissolution flux, Jp infinity M-1.15. The parameter Cp.dis, defined as the polymer disentanglement concentration or the polymer concentration at the tablet-diffusion layer interface, was a key parameter in that mathematical-model. The scaling law of Jp infinity M-1.15 indicates that the matrix dissolution rate decrease sharply with M at low M and gradually approaches a plateau as M becomes large. The plateau characteristics of Jp with M is consistent with the limiting drug release rate observed for HPMC-containing matrices, suggesting the critical role matrix dissolution plays in drug release.