目的 以盐酸鲁拉西酮（LH）为模型药制备触变胶型口服混悬液，考察其流变学测定样品处理方法，评价LH口服混悬液流变学特征。方法 以盐酸鲁拉西酮（LH）为模型药，以微晶纤维素-羧甲基纤维素钠（MCC/CMC-Na）为助悬剂，制备触变胶型口服混悬液。采用药典方法进行沉降体积比和粒度分布测定。采用流变仪，以黏度-时间曲线和触变环面积为指标，进行样品处理方法考察，包括取样工具考察、振摇时间考察、静置恢复时间考察、取样部位考察。采用流变仪对盐酸鲁拉西酮口服混悬液进行流变学性质评价表征，包括流动曲线与黏度曲线、线性黏弹区、触变性测定、频率扫描、黏度温度扫描。结果 LH口服混悬液沉降体积比为0.96±0.01，稳定性良好；粒径0.190～117.100 μm，符合混悬剂要求。选择样品处理方法为充分振摇2 min再静置24 h后，用直径2 mm塑料滴管移取中部位置的LH口服混悬液进行流变测定，该样品处理方法精密度良好。流变学表征测试结果表明LH口服混悬液具有假塑性，有剪切变稀的性质，其24 h样品的屈服应力为1.77 Pa；线性黏弹区应变范围在0.01%～0.70%，线性黏弹区较宽；具有较强触变性；在0～60℃条件下，温度变化基本上不会对LH口服混悬液稳定性造成明显影响，样品在常温储存即可。结论 建立的样品处理方法精密度良好，且具有一定区分力； LH口服混悬液的流变学性质既有利于静止状态下样品的储存稳定性，也有助于生产过程中灌装、使用过程中倾倒。

Objective A thixotropic gel type oral suspension of lurasidone hydrochloride (LH) was prepared as a model drug, and the sample processing methods for rheological determination were investigated to evaluate the rheological characteristics of the LH oral suspension. Methods The LH oral suspension was prepared with microcrystalline cellulose-carboxymethyl cellulose sodium (MCC/CMC-Na) as the suspending agent. The sedimentation volume ratio and particle size distribution were determined by the pharmacopoeia method. The rheometer was used to investigate the sample processing methods, including the examination of sampling tools, shaking time, static recovery time, and sampling position, with the viscosity-time curve and thixotropic ring area as the indicators. The rheological properties of the LH oral suspension were evaluated and characterized by the rheometer, in cluding flow curve and viscosity curve, linear viscoelastic region, thixotropy determination, frequency sweep, and viscosity-temperature scan. Results The sedimentation volume ratio of the LH oral suspension was 0.96 ±0.01, indicating good stability; the particle size was 0.190—117.100 μm, meeting the requirements of suspensions. The sample processing method was selected as shaking thoroughly for 2 min and then standing for 24 h, followed by taking the LH oral suspension from the middle position with a 2 mm diameter plastic dropper for rheological determination. This sample processing method had good precision. The rheological characterization test results showed that the LH oral suspension had pseudoplasticity and shear thinning properties, with a yield stress of 1.77 Pa for the 24 h sample; the strain range of the linear viscoelastic region was 0.01%—0.70%, indicating a wide linear viscoelastic region; it had strong thixotropy; under the conditions of 0—60 ℃, the temperature change basically had no significant impact on the stability of the LH oral suspension, and the sample could be stored at room temperature. Conclusion The established sample processing method had good precision and certain discrimination; the rheological properties of the LH oral suspension were beneficial to the storage stability of the sample in the static state and also facilitated filling during production and pouring during use.

R283.6