(159g) Characterizing the Porosity-Performance Relationship of Matrix Tablets Containing Intra- and/Or Extra-Granular HPMC Materials With Different Morphological Attributes

The purpose of this work is to use mercury porosimetry as a tool to characterize pore sizes and distribution within tablets. We examine how tablet porosity corresponds with other tablet physical and performance properties and changes with HMPC morphology, HPMC location (intra- and/or extra-granular), and compression force.

Two model APIs were chosen: gliclazide, a low-dose, high-potency very slightly soluble drug, and metformin HCl, a high-dose, low-potency highly soluble drug. Formulations were roller compacted using 2 tons of force, milled, and subsequently compressed at forces ranging from 3,000 to 8,500 lbf depending on the API. Either a granular or fibrous morphology of HPMC was included in the formulation intra- or extra-granularly, and a combination of intra- and extra-granular HPMC was also investigated. Roller compacted ribbons were evaluated visually. The milled granules were analyzed for density, flow, and particle size distribution. Tablets were characterized primarily for porosity, physical properties, and modified-release performance. Tablet pore size and distribution was measured using mercury intrusion porosimetry. Intrusion pressures ranged from 0.5 to 60,000 psia, allowing for detection of pore sizes from 0.003-400 μm in diameter.

Results showed that friability was acceptable in all cases, and was always below 0.60% regardless of compression force, HPMC morphology, or HPMC location. Porosity ranged from 9 to 15% and average pore diameter ranged from 0.27 to 0.75 μm. A higher tablet compression force resulted in reduced porosity. Lower tablet porosities and smaller average pore sizes were obtained with fibrous HPMC. Lower porosities also corresponded with higher tablet hardness. Drug release ranged from 29 to 60% at 12 h and 48 to 85% at 24 h, depending somewhat upon HPMC morphology and compression force, but more significantly upon the location of HPMC. More details will be presented on the relationships observed between HPMC morphology and location, formulation process variables, and tablet physical and performance properties.

These findings assist the formulator in understanding the relationships between tableting processing variables, raw material characteristics, and the resulting tablet physical and performance attributes.