Design of xerogel pill with good swallowing performance through wet milling and drop freeze-drying processes
Design of xerogel pill with good swallowing performance through wet milling and drop freeze-drying processes
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DOI：
10.1016/j.ijpharm.2022.121783
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发表时间：
2022-05-13
影响因子：
5.8
通讯作者：
Niwa, Toshiyuki
中科院分区：
文献类型：
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作者：
Asai, Rando;Takeuchi, Teruna;Niwa, Toshiyuki
一种具有剂量调节和辅助吞咽功能的新型剂型被称为“干凝胶丸”，用于儿科或老年患者。它是一种多单位剂型，其中一次剂量被分成几粒。这种药丸是双层结构的小球体，内部是药物核心，外部是干燥凝胶层（干凝胶壳）。本研究采用湿磨和滴冷冻干燥相结合的方法，建立了干凝胶丸的制备方法（配方和工艺）。以盐酸非索非那定（FXF）为低水溶性模型药物。黄原胶（XG）是一种胶凝剂，用于获得光滑柔软的口感。将湿磨法制备的FXF纳米悬浮液作为内部流体，将XG溶液作为外部流体，分别送入由中心喷嘴和外围喷嘴组成的双流体喷嘴。两种流体同心滴入液氮中，形成双结构液滴。经过冷冻干燥过程，形成了干凝胶丸。甘露醇（MNT）作为填充物，与这两种液体共同配制，以增强药丸的物理强度。制成的药丸直径约5-6毫米，呈球形，大小均匀，密度低，易于吞咽，与水接触后迅速凝胶化。根据外液中XG的含量，每片中FXF的含量为7- 9mg。FXF用量的相对标准偏差（RSD）在3 ~ 10%范围内变化，表明其含量均匀性可以接受为5片及以上的复合剂量单位。据推测，要使干凝胶丸投入实际使用，还需要进一步改进其物理强度和药物含量的均匀性。
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.