MEDELPHARM Technical Bulletin – Formulation Development and Compaction of Itraconazole Amorphous Solid Dispersion Tablets

The latest technical bulletin from research-based manufacturer and powder compaction specialists MEDELPHARM explores a method based on Quality by Design (QbD) principles to highlight the role of inorganic salts in promoting more rapid tablet dissolution.

Itraconazole (ITZ), a drug exhibiting low solubility requires formulation enhancement to achieve enhanced bioavailability. To tackle this problem amorphous solid dispersions (ASDS) of ITZ in a polymer matrix (Kollidon® VA64) were produced using the Hot Melt Extrusion (HME) process. ASDS improve the poor solubility of the BCS Class II drug, compared to its pure crystalline form, however this enhancement is impaired at the tableting stage due to the high dose (100 mg) requirement and the presence of high polymer content (70%).

In this study, a fast-screening approach to formulation development using the STYL’One Nano compaction simulator was adopted. Initially number of preliminary formulations were compacted, followed by the introduction of a novel strategy using salts to enhance the disintegration and dissolution properties. Five inorganic salts were investigated, sodium chloride (NaCl), potassium chloride (KCl), potassium bicarbonate (KHCO3), potassium dihydrogen orthophosphate (KH2PO4) and potassium bromide (KBr). These kosmotropic salts are debated to compete for water hydration near the polymer chain, hence preventing polymer gelation and therefore facilitating disintegration and dissolution.

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