目的 以鹽酸魯拉西酮（LH）為模型藥制備觸變膠型口服混懸液，考察其流變學(xué)測定樣品處理方法，評價(jià)LH口服混懸液流變學(xué)特征。方法 以鹽酸魯拉西酮（LH）為模型藥，以微晶纖維素-羧甲基纖維素鈉（MCC/CMC-Na）為助懸劑，制備觸變膠型口服混懸液。采用藥典方法進(jìn)行沉降體積比和粒度分布測定。采用流變儀，以黏度-時(shí)間曲線和觸變環(huán)面積為指標(biāo)，進(jìn)行樣品處理方法考察，包括取樣工具考察、振搖時(shí)間考察、靜置恢復(fù)時(shí)間考察、取樣部位考察。采用流變儀對鹽酸魯拉西酮口服混懸液進(jìn)行流變學(xué)性質(zhì)評價(jià)表征，包括流動(dòng)曲線與黏度曲線、線性黏彈區(qū)、觸變性測定、頻率掃描、黏度溫度掃描。結(jié)果 LH口服混懸液沉降體積比為0.96±0.01，穩(wěn)定性良好；粒徑0.190～117.100 μm，符合混懸劑要求。選擇樣品處理方法為充分振搖2 min再靜置24 h后，用直徑2 mm塑料滴管移取中部位置的LH口服混懸液進(jìn)行流變測定，該樣品處理方法精密度良好。流變學(xué)表征測試結(jié)果表明LH口服混懸液具有假塑性，有剪切變稀的性質(zhì)，其24 h樣品的屈服應(yīng)力為1.77 Pa；線性黏彈區(qū)應(yīng)變范圍在0.01%～0.70%，線性黏彈區(qū)較寬；具有較強(qiáng)觸變性；在0～60℃條件下，溫度變化基本上不會對LH口服混懸液穩(wěn)定性造成明顯影響，樣品在常溫儲存即可。結(jié)論 建立的樣品處理方法精密度良好，且具有一定區(qū)分力； LH口服混懸液的流變學(xué)性質(zhì)既有利于靜止?fàn)顟B(tài)下樣品的儲存穩(wěn)定性，也有助于生產(chǎn)過程中灌裝、使用過程中傾倒。

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