Effect of varying the restriction degree of 4-aminopyridine release from HPMC matrices on the mechanism controlling the process

Among different technological variables that influence drug release from hydrophilic matrices, different proportions of the polymer and a water-soluble excipient have been used to control the drug release properties. These variables were used to modify the drug release rate and to examine its effect on the mechanism controlling the process. Tablets of the model drug 4-aminopyridine (4-AP) were prepared varying the matrix proportion of hydroxypropyl methylcellulose (HPMC) and citric acid (CA). The matrices release behavior (USP apparatus 2, paddle, at 50rpm) was examined using 0.1N HCl and 0.2M phosphate buffer as dissolution media. Dissolution curves were described by M_t/M_inf=ktⁿ, applied separately for each dissolution medium. The increase of the HPMC matrix content reduced the release rate of the drug. The release mechanism showed a linear trend toward higher n values with a continuous reduction of drug release. The addition of increasing proportions of CA produced the opposite. An increasing drug release rate produced logarithmic decreasing n values. The results demonstrate, as a general rule, that every restriction of the drug release rate is associated with increasing values of the mechanism-indicating exponent n. This relationship means a logarithmic movement away from a release mechanism controlled by diffusion toward a mechanism controlled by relaxation, erosion and dissolution of the polymeric matrix as the drug release rate is restricted. These results are attributed to an increasing hydration and dissolution of the polymeric matrix, as the drug release is subject to limitation.