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

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.

[Homogeneity of Two Semisolid Formulations Using Simple In-tube Mixing Method].

To accelerate therapeutic effects, the mixtures of two or more topical pharmaceutical products having different medicinal purposes are often applied in the medical field. In this study, we aimed to develop a simple mixing method/procedure to achieve excellent homogeneity in the mixture of two topical products, a steroidal ointment and a skin moisturizer. To assess an in-tube mixing method as a simple mixing procedure, we injected both topical products into an empty resin tube, a flexible hollow tube with an open end that can be closed on one side, and a closed end on the other, removed as less air as possible inside the tube, and then thermocompressed (sealed) the open end to close it. The two topical products were then mixed uniformly by repeated finger pressure along the longitudinal axis of the tube. The homogeneity of the two topical products in the tube was evaluated by measuring the content of methyl paraoxybenzoate (MP), an additive loaded in the skin moisturizer. In addition, the mixability was qualitatively evaluated from the distribution of white petrolatum, another additive loaded in the steroid ointment, using Raman spectroscopy. As a result, the measured value of MP relative to the label claim was in the range of 100±12%, and the coefficients of variation value was also less than 12%. These results indicate that the in-tube mixing method using two topical products is approximately hologenetic preparations that do not cause therapeutic problems.

Design of xerogel pill with good swallowing performance through wet milling and drop freeze-drying processes.

A novel dosage form with dose-adjusting and swallow-assisting functions, named "xerogel pills," was developed for pediatric or geriatric patients. It is a multiple-unit dosage form in which a single dose is divided into several pills. The pills are double-structured small spheres with an inner drug core and an outer dried-gel layer (xerogel shell). In this research, the preparing method (formulation and process) of the xerogel pills was established by using a combination of wet-milling and drop freeze-drying (DFD) techniques. Fexofenadine hydrochloride (FXF) was used as a poorly water-soluble model drug. Xanthan gum (XG), a gelling agent, was formulated to attain a smooth and soft mouth-feeling. The internal fluid consisting of the FXF nanosuspension prepared through the wet-milling process and the external fluid consisting of an XG solution were separately fed to a two-fluids nozzle composed of central and peripheral nozzles. Both fluids were concentrically dropped together into liquid nitrogen to construct double-structured droplets. After the freeze-drying process, the xerogel pills were formed. Mannitol (MNT), as a filler, was co-formulated with both fluids to strengthen the pills physically. The resultant pills were around 5-6 mm in diameter with a spherical shape, uniform size, and low density, enabling them to be easily swallowed, and quickly gelled upon contact with water. The FXF amount in one pill was 7-9 mg, depending on the XG loading in the external fluid. The relative standard deviation (RSD) of the FXF amount were varied in the range of around 3-10%, suggesting that the content uniformity would be acceptable as a composite dosage unit containing five or more pills. It was assumed that further improvements of the physical strength and drug content uniformity would be required to introduce the xerogel pills to practical use.