高速搅拌制粒过程参数对穿心莲提取物混合粉体成粒性的影响
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摘要
目的研究高速搅拌制粒过程参数与混合粉体成粒性的相关性。方法模型药物穿心莲提取物分别与淀粉或微晶纤维素等比例混合制备混合粉体,采用部分因子筛选实验设计设置过程参数,高速搅拌制备颗粒。以颗粒收率、团块和细粉比例为指标评价成粒行为,采用逐步回归法分析过程参数对粉体成粒行为的影响,并采用标准最小二乘法建立成粒性与过程参数数学模型,预测颗粒收率。结果过程参数对粉体成粒性具有较大的影响,且对淀粉和微晶纤维素混合粉体表现出不一致的作用。模型预测颗粒收率为(66.7±3.7)%,实际测定淀粉和微晶纤维素混合粉体颗粒收率分别为68.9%,66.1%。结论所建立的模型能够较好地预测颗粒收率,为优化高速搅拌制粒过程参数、提高颗粒收率提供了研究基础。
OBJECTIVE To investigate the relationship between the process parameters and granulation behavior during high shear granulation process. METHODS Andrographis extract was utilized as a model drug and mixed with microcrystalline cellulose(MCC)or soluble starch at the ratio of 1∶ 1 by weigh,respectively. The process parameters were selected according to fractional factorial experiment. The granules were prepared by using high shear granulation. The aggregation behavior was evaluated by granule yield and ratio of lumps and fine powder. The effect of process parameters on granulation behavior was analyzed through stepwise regression. Standard least squares regression analysis was used to establish the mathematical model of granule yield. RESULTS The process parameters had different effects on the granulation behaviors of MCC and starch mixtures. The granule yield predicted by the fitting model was(66. 66 ± 3. 7)%,and the measured values for MCC and starch mixture were 68. 9% and 66. 1%,respectively. CONCULSION The established mathematical model is useful in predicting the performance of materials duing high shear granulation process. Understanding the impact of process parameters on granulation behavior provides the basis of modulating granulation parameters in order to optimize product performance and improve the yield.
OBJECTIVE To investigate the relationship between the process parameters and granulation behavior during high shear granulation process. METHODS Andrographis extract was utilized as a model drug and mixed with microcrystalline cellulose(MCC)or soluble starch at the ratio of 1∶ 1 by weigh,respectively. The process parameters were selected according to fractional factorial experiment. The granules were prepared by using high shear granulation. The aggregation behavior was evaluated by granule yield and ratio of lumps and fine powder. The effect of process parameters on granulation behavior was analyzed through stepwise regression. Standard least squares regression analysis was used to establish the mathematical model of granule yield. RESULTS The process parameters had different effects on the granulation behaviors of MCC and starch mixtures. The granule yield predicted by the fitting model was(66. 66 ± 3. 7)%,and the measured values for MCC and starch mixture were 68. 9% and 66. 1%,respectively. CONCULSION The established mathematical model is useful in predicting the performance of materials duing high shear granulation process. Understanding the impact of process parameters on granulation behavior provides the basis of modulating granulation parameters in order to optimize product performance and improve the yield.
引文
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[12]VEMAVARAPU C,SURAPANENI M,HUSSAIN M,et al.Role of drug substance material properties in the processibility and performance of a wet granulated product[J].Int J Pharm,2009,374(1-2):96-105.
[13]LE P K,AVONTUUR P,HOUNSLOW M J,et al.A microscopic study of granulation mechanisms and their effect on granule properties[J].Powder Technol,2011,206(1-2):18-24.
[2]LI C,LIU H,WANG C G,et al.Relationship between granule flowability under different humidity and quality of guaifenesin sustained release tablet[J].Chin Pharm J(中国药学杂志),2012,47(5):358-361.
[3]SHI L,FENG Y,SUN C C,et al.Initial moisture content in raw material can profoundly influence high shear wet granulation process[J].Int J Pharm,2011,416(1):43-48.
[4]HE Q,LI W Z,WANG J J,et al.Influence of different excipients on hygroscopic property of raw material(dry extract powder)in yuxianling granules[J].Chin Pharm J(中国药学杂志),2007,42(10):753-757.
[5]TAN Q S,GUO Z,CHANG D,et al.Influence of process parameters of high shear granulation through preparing creat extract with different flowability[J].J Shenyang Pharm Univ(沈阳药科大学学报),2010,27(2):81-86.
[6]CHANG R K,RAW A,LIONBERGER R,et al.Generic development of topical dermatologic products,partⅡ:Quality by design for topical semisolid products[J].AAPS J,2013,15(3):674-683.
[7]RITALA M,HOLM P,SCHAEFER T,et al.Influence of liquid bonding strength on power consumption during granulation in a high shear mixer[J].Drug Dev Ind Pharm,1988,14(8):1041-1060.
[8]KNIGHT P C.An investigation of the kinetics of granulation using a high shear mixer[J].Powder Technol,1993,77(2):159-169.
[9]BADAWY S F,NARANG A S,LAMARCHE K,et al.Mechanistic basis for the effects of process parameters on quality attributes in high shear wet granulation[J].Int J Pharm,2012,439(1-2):324-333.
[10]MANGWANDI C,LIU J T,ALBADARIN A B,et al.Alternative method for producing organic fertiliser from anaerobic digestion liquor and limestone powder:High shear wet granulation[J].Powder Technol,2013,233:245-254.
[11]LIU L X,LITSTER J D,IVESON S M,et al.Coalescence of deformable granules in wet granulation processes[J].AIChE J,2000,46(3):529-539.
[12]VEMAVARAPU C,SURAPANENI M,HUSSAIN M,et al.Role of drug substance material properties in the processibility and performance of a wet granulated product[J].Int J Pharm,2009,374(1-2):96-105.
[13]LE P K,AVONTUUR P,HOUNSLOW M J,et al.A microscopic study of granulation mechanisms and their effect on granule properties[J].Powder Technol,2011,206(1-2):18-24.