Characterisation of particle properties and compaction behaviour of hydroxypropyl methylcellulose with different degrees of methoxy/ hydroxypropyl substitution

The particle characteristics and compaction behaviour of hydroxypropyl meth ylcellulose (HPMC) powders from two different suppliers were studied regard ing effects of methoxy/hydroxypropyl substitution. Samples included Methoce l K4M (low substitution ratio), E4M (medium) and F4M (high) and the corresp onding substitution ratios from Metolose: 90 SH 4000, 60 SH 4000, and 65 SH 4000. Characterisation of the particle properties and compaction behaviour of the pure polymers suggested that reported differences in drug release b ehaviour of Methocel E4M compared with the other two powders may be related to the lower powder surface area, differing particle morphology and lower fragmentation propensity during compaction. In addition, compacts of Methoc el E4M were weaker when tested in both axial and radial directions and had different porosity and elastic recovery properties. There were no differenc es between the polymers in degree of disorder, as evaluated by solid-state nuclear magnetic resonance spectroscopy. The different behaviour of Methoce l E4M could, however, be related to the overall higher total degree of subs titution of this polymer and in particular the high content of methoxy grou ps compared to the other polymers. The methoxy substituent is hydrophobic a nd may, when present in sufficiently high concentrations, change the partic ulate and mechanical properties of the powder, thus potentially affecting t he compactability. The high content of methoxy groups might also decrease t he development of inter- and intraparticulate hydrogen bonds during compact ion, and suppress the actions of the hydrophilic hydroxypropyl groups, both of which could affect drug release. (C) 1999 Elsevier Science B.V. All rig hts reserved.