The effect of HPMC particle size on the drug release rate and the percolation threshold in extended-release mini-tablets.

The particle size of HPMC is a critical factor that can influence drug release rate from hydrophilic matrix systems. Percolation theory is a statistical tool which is used to study the disorder of particles in a lattice of a sample. The percolation threshold is the point at which a component is dominant in a cluster resulting in significant changes in drug release rates. Mini-tablets are compact dosage forms of 1.5-4 mm diameter, which have potential benefits in the delivery of drug to some patient groups such as pediatrics. In this study, the effect of HPMC particle size on hydrocortisone release and its associated percolation threshold for mini-tablets and tablets was assessed. For both mini-tablets and tablets, large polymer particles reduced tensile strength, but increased the drug release rate and the percolation threshold. Upon hydration, compacts with 45-125 μm HPMC particles formed a strong gel layer with low porosity, reducing hydrocortisone release rates. In comparison, faster drug release rates were obtained when 125-355 µm HPMC particles were used, due to the greater pore sizes that resulted in the formation of a weaker gel. Using 125-355 µm HPMC particles increased the percolation threshold for tablets and to a greater extent for mini-tablets. This work has demonstrated the importance of HPMC particle size in ER matrices, the effects of which are even more obvious for mini-tablets.