以氢氯噻嗪(HCTZ)/氯沙坦钾(LOS-K)为模型药物,通过对混合粉末的压片性能和力学性能的考察,确定配方和制备因素,其次是D-最优混合料实验设计,以优化最终参数。乳糖一水合物的类型和数量(SuperTab®14SD,19.53-26.91%),微晶纤维素(MCCPH102,32.86-43.31%),预糊化淀粉(淀粉-1500,10.96-15.91%),和硬脂酸镁(0.7%)根据压缩功测定,应力松弛曲线,和Py值。然后,通过Kawakita方程研究了混合粉末的压缩机理,夏皮罗方程,和Heckel分析,并且将混合粉末分类为II类粉末。推荐压实压力(150-300MPa)和压片速度(1200-2400Tab/h)。D-最佳混合物实验设计用于选择最佳配方(No1,26.027%乳糖一水合物,32.811%MCCPH102,15.462%预胶化淀粉)根据药物溶出度、使用Hyzaar®片剂作为对照。在比格犬口服后,编号之间的生物利用度没有显着差异。1片和HCTZ中的Hyzaar®片,氯沙坦羧酸(E-3174),和LOS-K(F<F0.05)。因此,根据混合粉末的压缩性能和机械性能以及片剂的质量,确定了配方和制备因素,这被证明是一种可行的直接粉末压缩方法。
Hydrochlorothiazide (HCTZ)/losartan potassium (LOS-K) was used as a model drug to prepare compound tablets through the investigation of the compression and mechanical properties of mixed powders to determine the formulation and preparation factors, followed by D-optimal mixture experimental design to optimize the final parameters. The type and amount of lactose monohydrate (SuperTab®14SD, 19.53−26.91%), microcrystalline cellulose (MCC PH102, 32.86−43.31%), pre-gelatinized starch (Starch-1500, 10.96−15.91%), and magnesium stearate (0.7%) were determined according to the compressive work, stress relaxation curves, and Py value. Then, the compression mechanism of the mixed powder was investigated by the Kawakita equation, Shapiro equation, and Heckel analysis, and the mixed powder was classified as a Class-II powder. The compaction pressure (150−300 MPa) and tableting speed (1200−2400 Tab/h) were recommended. A D-optimal mixture experimental design was utilized to select the optimal formulation (No 1, 26.027% lactose monohydrate, 32.811% MCC PH102, and 15.462% pregelatinized starch) according to the drug dissolution rate, using Hyzaar® tablets as a control. Following oral administration in beagle dogs, there were no significant differences in bioavailability between the No. 1 tablet and the Hyzaar® tablet in HCTZ, losartan carboxylic acid (E-3174), and LOS-K (F < F0.05). Thus, formulation and preparation factors were determined according to the combination of the compression and mechanical properties of the mixed powder and quality of tablets, which was demonstrated to be a feasible method in direct powder compression.