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

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The particle size of HPMC plays a crucial role in influencing the drug release rate from hydrophilic matrix systems. Percolation theory, a statistical tool, is employed to analyze the disorder of particles within a lattice structure. The percolation threshold marks the point where a component dominates a cluster, leading to significant alterations in drug release rates. Mini-tablets, compact dosage forms with diameters ranging from 1.5 to 4 mm, offer potential advantages in drug delivery, particularly for specific patient groups such as pediatrics. This study investigates the impact of HPMC particle size on hydrocortisone release and the associated percolation threshold for both mini-tablets and conventional tablets. For both mini-tablets and tablets, larger polymer particles were found to decrease tensile strength while increasing the drug release rate and percolation threshold. Upon hydration, compacts with HPMC particles ranging from 45 to 125 μm formed a robust gel layer with low porosity, leading to reduced hydrocortisone release rates. In contrast, faster drug release rates were observed when using HPMC particles in the range of 125 to 355 µm, attributed to larger pore sizes resulting in the formation of a weaker gel. The use of 125 to 355 µm HPMC particles increased the percolation threshold for tablets and, to a greater extent, for mini-tablets. This study highlights the significant role of HPMC particle size in extended-release matrices, with more pronounced effects observed in mini-tablets.
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