Comparative evaluation of rate of hydration and matrix erosion of HEC and HPC and study of drug release from their matrices

Abstract

Hydrophilic polymers, in contact with the dissolution medium, may swell and make a continuous gel layer, erode or undergo combination of the two. The swelling action of these polymers is controlled by the rate of their hydration in the dissolution medium. The extent of polymer swelling, relative mobilities of dissolution medium and drug, and matrix erosion dictate the kinetics as well as mechanism of drug release from the polymeric matrices. The objective of the present investigations was to study the rate of hydration and the rate of matrix erosion of two hydrophilic, non-ionic cellulose ethers, i.e., hydroxyethylcellulose (HEC) and hydroxypropylcellulose (HPC), and to compare the kinetics and mechanism of drug release from their matrices. Chlorpheniramine maleate was used as the model drug. Matrix tablets containing chlorpheniramine maleate, HEC or HPC and dicalcium phosphate were compressed at 156 MPa pressure. The rate of hydration of the polymer, rate of erosion of the matrices and in vitro drug release studies were carried out in phosphate buffer (pH 7.4). The hydration studies of the two polymers demonstrated that due to relatively larger water uptake, the degree of swelling of HEC matrices was considerably higher as compared to the HPC matrices. Also, HEC matrices exhibited relatively higher erosion as compared to HPC matrices. The drug release from HEC matrices occurred by non-Fickian transport, i.e., combination of drug diffusion and polymer swelling, while drug release from HPC matrices was controlled primarily by diffusion through pores and channels in the structure. The t 50%, time to reach 50% drug release, for HEC matrices was 4.8 h and that for HPC matrices was 6.5 h which indicates that a higher polymer level was needed in the case of HEC matrices to sustain the drug release for up to 12 h of dissolution as compared to HPC matrices due to relatively higher hydrophilicity of HEC.