Compaction of co-amorphous griseofulvin/amino acid powders at elevated temperatures and their "in-tablet" stability.

OBJECTIVES: Equimolar griseofulvin (GRI) co-amorphous systems (CAMS) with amino-acids (AAs) were prepared by hot-melt-extrusion and evaluated for compactibility and "in-tablet" stability at ambient (21-23°C), intermediate (43-46°C), and high temperature [87-92°C, near CAMS' glass transition (Tg)]. METHODS: Compression was studied by "in-die" measurements. Tablet strength and morphology were evaluated by diametrical compression and electron microscopy, moisture uptake by dynamic sorption, and solid-state stability by X-ray powder diffraction and micro-spatially offset low-frequency Raman spectroscopy. KEY FINDINGS: CAMS powders exhibited lower Heckel yield pressure (Py) and compaction work (Wc) but higher elastic recovery than crystalline physical mixtures (PMs). However, the strength of PM and CAMS tablets prepared at low or intermediate temperatures were comparable, due to balancing the effects of deformability (Py) and surface interaction (Wc). Compression near CAMS' Tg gave weak tablets. CAMS tablets exhibited low moisture sorption and remained amorphous after 90 days at 45°C/75% relative humidity, confirming excellent stability, whereas tablets of amorphous drug recrystallized after 30 days. Low-frequency Raman spectroscopy revealed details that escaped crystallography. Isolated residual drug crystals were detected, suggesting further finer-tuning for optimal GRI/AA ratio. CONCLUSION: These findings indicate the potential of GRI/AA CAMS for direct compression providing that adequate flowability is assured.