星点设计-效应面法优化盐酸莫西沙星片的制备工艺

Optimization of the Preparation Process of Moxifloxacin Hydrochloride Tablets by Central Composite Design -Response Surface Methodology

目的:利用星点设计-效应面法优化盐酸莫西沙星片的制备工艺。方法:在单因素试验的基础上,采用三因素五水平的星点试验考察各因素对盐酸莫西沙星片剂的影响,选择影响较大的制粒用水量(A)、搅拌速度(B)和硬脂酸镁的混合时间(C)3个因素作为星点设计试验的考察因素,以总混颗粒的粒度分布(R1)、总混颗粒的可压性(R2)、休止角(R3)、卡尔指数(R4)、软材的性状(R5)以及素片在5 min时间点的溶出量(R6)作为评价指标,拟合二次多项式方程,选取最优制剂工艺参数并进行验证。结果:最优制剂工艺参数:制粒过程中制粒用水量为32.1%、搅拌速度为402 r/min,硬脂酸镁的混合时间为6.3 min;按照上述工艺参数进行试验,莫西沙星软材球状物的比重为15%,总混颗粒的休止角为36.4°,总混颗粒40~80目截留的占41.75%,素片在5 min时间点的溶出量在83%以上;实测值与预测值偏差低于5%,模型拟合效果良好。结论:星点设计-效应面法优化可用于盐酸莫西沙星的工艺优化,所建模型具有较好的预测能力和实用性,所制备的自研制剂释药行为与原研相似,可为后续研究提供依据。

Objective:To optimize the formulation process of moxifloxacin hydrochloride tablets using the central composite design-response surface methodology.Methods:On the basis of single-factor experiments,a three-factor,five-level central composite design is used to investigate the effects of various factors on the formulation process of moxifloxacin hydrochloride tablets.Three factors,namely the amount of water used for granulation(A),the speed of stirring(B),and the mixing time of magnesium stearate(C),are selected as the factors to be investigated in the central composite design,meanwhile the particle size distribution of total blended particles(R1),the compressibility of the total mixed particles(R2),the repose angle(R3),Carr’s index(R4),the properties of soft materials(R5),and the dissolution of the core tablets at 5 min(R6)are used as indicators to fit a quadratic polynomial equation to optimize and validate the formulation process parameters.Results:The optimal formulation process parameters as follows:32.1%water for granulation,402 r/min for stirring and chopping,and 6.3 min for mixing of magnesium stearate during the granulation process;the agglomerate took up 15%of wet mass after wet granulation,the repose angle of the final blend is 36.4°,particles between 40 and 80 mesh amounted to 41.75%in the final blend,and the dissolution of the uncoated tablets at the 5 min time point is above 83%;the deviation between the measured value and the predicted value is less than 5%,and the model fitting effect is good.Conclusion:The moxifloxacin hydrochloride tablets after optimization of formulation process parameters by the central composite design-response surface method has good prediction ability and practicability. The drug release behavior of the prepared self-developed agent is similar to that of the original study, which can provide a basis for subsequent studies.