Design of easily swallowable xerogel pill with enough physical strength through hardening-process under heating and humidification.

ABSTRACT

The xerogel pill has been developed as a novel dosage form with dose-adjusting and swallow-assisting functions by using drop freeze-drying (DFD) technique. It was double-structured small sphere composed of an inner drug core and an outer dried-gel layer, however, had problem of insufficient physical strength. In this study, it was attempted to use dextrin (DEX), one of oligosaccharides, to strengthen the xerogel pill. DEX was co-dissolved in the dropping fluid in the DFD process and co-loaded in the conventional pill, which was mainly composed of mannitol (MNT) as a filler, to prepare the rigid body. DEX-loaded pill could be successfully prepared with high recovery (>90 %) by optimizing the ratio of DEX and MNT. Further, the representative pills with and without DEX (P-DEX and P-MNT, respectively) were hardening-processed under humidification. The physical strength of P-DEX pill was significantly increased when humidified under severe condition, resulting in enough hardness (>5N) and friability (<1.0 %). Processed P-DEX was found to have dense structure covered with a thick outer shell, which would be formed by interparticle bridge of DEX. It was also found that processed P-DEX pill suppressed initial drug dissolution significantly and exhibited sustained dissolution behavior, suggesting the potential function of bitter taste masking. Processed P-DEX pill had excellent sliding behavior with low friction forces as a result of lubricant effect of xanthan gum (XG) surrounding the pills. Furthermore, the sliding test also suggested that processed P-DEX pill had hard candy-like texture, in contrast unprocessed P-DEX pill had orally disintegrating (OD) tablet-like texture. Various xerogel pills with such different swallowing texture would have a potential to accommodate the children's preferences when taking medication.