Water distribution studies within cellulose ethers using differential scanning calorimetry. 2. Effect of polymer substitution type and drug addition.

The distribution of water within gels composed of a range of cellulose ether polymers of similar molecular weights (viscosity grades of 4000-6000 cP) but varying substitution types and levels was assessed by differential scanning calorimetry (DSC). Water loosely bound to the polymer was detected as one or more events appearing at the low-temperature side of the main endotherm for the melting of free water in DSC scans. Polymer substitution types and levels, and added drugs (50 mM propranolol hydrochloride or 50 mM diclofenac sodium) influenced the appearance of these melting events. Hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose (HPMC F4M) gels showed behavior different to that of the other polymers studied. It is thought that any water binding to HPC gels is tightly attached and is not visible as pre-endothermic events on DSC scans. The amount of water bound per polymer repeating unit (PRU) was influenced by and related to the degree of hydrophilic and hydrophobic substitution on the polymer backbone and by the inclusion of either drug. HPC gels had the highest bound water content after 96 h and this was probably related to the high percentage of hydrophilic hydroxypropoxyl substitutions in this polymer. In contrast, methylcellulose (MC A4M) had the lowest bound water content after 96 h storage, and this was explained by the lack of hydrophilic hydroxypropoxyl substitutions in the polymer.