Intersupplier and interlot variability in hydroxypropyl celluloses: implications for theophylline release from matrix tablets

Abstract

The physical and physicochemical properties of three lots of high-viscosity hydroxypropylcellulose (HPC) (two lots from a Japanese supplier and one lot from a US supplier) were compared. The drug-release properties of theophylline matrix tablets prepared with the different polymers were also investigated. HPCs from the two suppliers showed clear differences in molecular weight, molecular structure, particle size distribution, particle shape, and water affinity. Furthermore, clear differences were observed in the time-course of drug release from tablets made with the different polymers. The differences in basic physical and physicochemical properties of the HPCs affect compression behaviour, the capacity for and time-course of water uptake, and the rheological properties of aqueous dispersions, which explains the observed differences in time-course of drug release. Molecular weight and particle size distribution are particularly important determinants of drug release properties. Abnormally rapid drug release was observed from tablets prepared with relatively small amounts of the highest-molecular-weight highest-particle-size HPC. This result, together with the fact that the time-course of drug release differs markedly between matrix tablets prepared with HPCs that come from different suppliers but that are nominally interchangeable (at least according to the criteria given in the US Pharmacopoeia), suggests that these two properties (mean molecular weight and particle size distribution) are of value for quality control of HPCs destined for use in the manufacture of matrix tablets.