正交试验法优选骨炎宁颗粒的喷雾制粒工艺

目的：选择骨炎宁颗粒喷雾制粒的最佳工艺条件。方法：应用正交试验法，采用喷雾干燥制粒机制粒并在流化床上进行干燥，以浸膏浓缩的相对比例、进风温度及入塔风压为考察因素，每个因素3个水平，以颗粒的成品率及半成品颗粒的含水量为考察指标。结果：三因素中以浸膏浓缩的相对比例A和入塔风压C的影响较显著（P〈0．05），而进风温度B的影响不显著。结论：骨炎宁颗粒喷雾制粒的最佳工艺条件为A3B1C3。即浓缩的相对比例为1：1．20，进风温度为90℃，入塔风压为负压1800Pa。     

清热感冒颗粒流化床制粒工艺研究

目的 探索研究清热感冒颗粒流化床制粒的最佳工艺.方法 采用正交试验法,以制粒收得率和颗粒水分为指标,探索清热感冒颗粒流化床制粒的最佳工艺条件.结果 清热感冒颗粒流化床制粒的最佳工艺条件为:进风量2000m3/h,进风温度78℃、进液速度20rpm.结论 本试验为清热感冒颗粒的工艺改进提供了依据.     

葛根汤颗粒一步制粒工艺研究

目的考察分析葛根汤颗粒一步制粒的工艺特点及影响因素。方法利用葛根汤颗粒处方中糊精作为一步制粒底料,葛根汤浸膏溶液直接喷雾混合制粒干燥,一步形成颗粒,采用正交试验方法,通过考察葛根汤浸膏溶液相对密度、进风温度、喷浆速度及雾化压力,以成品率、含量和水分作为考察指标,筛选出制备葛根汤颗粒的最优工艺。结果不同的工艺条件对该产品的颗粒成品率有较大影响的,其中浸膏溶液的浓度对成品率的影响最大、其次为进风温度和雾化压力,喷浆速度影响最小。因此确定葛根汤颗粒的工艺条件为葛根汤浸膏溶液相对密度为1.18¹.23,进风温度设定(120±5)℃,雾化压力为0.41.23,进风温度设定(120±5)℃,雾化压力为0.4⁰.6 MPa,喷浆速度为(0.5±0.1)kg·min-1。结论葛根汤颗粒一步制粒法优点明显,值得在生产中推广。     

跳骨片一步制粒工艺条件优选

目的优选跳骨片一步制粒的工艺条件。方法应用正交试验法,以制得的颗粒的粒度合格率的含水量为指标,对影响跳骨片一步制粒过程的因素进行考察。结果正交试验设计的4个因素中,喷雾速率影响最为显著;优选出的工艺条件为:喷雾速率为80g.m i-n 1,雾化压力为0.21M pa,进风温度为(100±2)℃,出风温度为(45±2)℃。     

一种流化床喷雾制粒技术在头孢克洛颗粒制备中的应用

目的:研究流化床制粒设备在头孢克洛颗粒制备中的应用.方法:采用正交试验法,选定进风温度、喷入粘合剂浓度、喷浆速度、进风量为考察因素,每个因素取3个水平,筛选头孢克洛颗粒流化床制粒的最佳工艺.结果:最佳工艺条件为粘合剂为10％PVPK30、进风温度70℃、喷入速度50mL· min-1,进风量为1400m3· h-1.结论:本方法生产工艺简单,自动化程度更高,是药物制剂现代化生产的一条良好途径.     

流化床喷雾制粒在枫蓼肠胃康无糖颗粒制备中的应用

目的研究流化床制粒设备在中药无糖颗粒制备中的应用.方法采用正交试验法,选定进风温度、喷入浸膏的相对密度、喷浆速度、进风量为考察因素,每个因素取3个水平,筛选枫蓼肠胃康无糖颗粒流化床制粒的最佳工艺.结果最佳工艺条件为浸膏的相对密度1.25,进风温度80℃,喷入速度40 mL·min-1,进风量为1 400 m3·h-1.结论本方法生产工艺简单,自动化程度更高,是中药制剂现代化生产的一条良好途径.     

小儿化痰止咳颗粒喷雾制粒工艺研究

目的探讨小儿化痰颗粒喷雾制粒工艺的最佳生产条件。方法采用正交设计法，以黏舍剂浓度、黏合剂用量、喷雾速度、制粒温度为可变因素，以合格颗粒收得率为指标，对影响因素进行研究。结果最佳生产条件为黏合剂明胶浓度为8．0％，用量为1．5％，喷雾速度为0.4kg／min，制粒温度为65℃。结论该生产工艺可操作性强，产品收得率高，质量稳定，适用于工业化生产。     

疏肝舒乳颗粒一步制粒工艺优选

目的：确定疏肝舒乳颗粒一步制粒工艺。方法：应用DPC-3型多功能制粒包衣机，按照L9（3^4）正交试验，以主药成分延胡索乙素含量为试验样品质量考核指标，优选工艺。结果：最佳生产工艺条件是A3B2C2D1，即将一定量的辅料置于制粒机中，开启引风机和加热器，使物料在流化状态下均匀升温至70℃，开启喷雾按钮，喷入中药浸膏，进料速度400g·min^-1，雾化压力0．25MPa，进风温度90℃，物料温度70℃，密切观察物料流化状态，直至浸膏全部喷入。继续干燥30min，降温出料。结论：一步制粒技术应用在该产品的生产中，工艺先进，改变了传统制粒工艺多环节，辅料用量大，劳动强度大等不足，提高了制剂水平，可用于疏肝舒乳颗粒的工业化生产。     

辛白鼻渊颗粒喷雾制粒工艺优选

目的 优选辛白鼻渊颗粒喷雾制粒的最佳工艺.方法 采用正交试验法,以喷雾干燥后药粉产量为考察指标优选工艺条件,并进行验证试验和成品质量考察.结果 最佳工艺参数为进风温度90℃,喷液转速6 r/min,风机频率45 Hz;薄层鉴别结果 显示,供试品溶液色谱中,在与黄芩苷和栀子苷对照品溶液色谱相应位置上显相同颜色的斑点;成品...     

骨得健颗粒一步制粒工艺研究

目的对一步制粒法制备骨得健颗粒的工艺进行优化。方法以颗粒的得率、水分和含量为考察指标,采用正交实验法对影响骨得健颗粒一步制粒过程的因素进行考察。结果 3个考察因素中喷雾速度对结果影响显著,最佳工艺条件为:喷液速度为10 mL·min-1,雾化压力为1.4 bar,进风温度为80℃。结论该工艺合理可行,产品稳定性好,为工业化生产提供了实验依据。     

Comparison of the granulation behavior of three different excipients in a laboratory fluidized bed granulator using statistical methods

The granulation process and, subsequently, the tableting behavior of the resulting granules of alpha-lactose-monohydrate, dicalcium phosphate anhydrous, and potato starch were investigated using statistical designs. The three substances were chosen due to their differences in granulation and tableting behavior, such as water solubility, swelling, and compressional properties. Granulation process variables, namely the inlet air temperature, spray rate, binder concentration of granulating solution, and inlet air flow rate were investigated. A central composite design was applied to study the granulation of alpha-lactose-monohydrate. Granulations of dicalcium phosphate and potato starch were investigated using a 2(3) factorial design, in which the effects of the inlet air temperature, spray rate, and binder concentration were considered. To compare the granulation behavior of theses substances the particle size distribution, angle of repose, and yield of the granules were used as responses for the statistical designs. The granules were compressed into tablets and the tensile strength was used as an additional statistical response. Based on the process parameters, models were developed using multiple regression modeling for each examined response. These models were then used to optimize the granulation process that provides granules with a Sauter mean diameter of D32 between 300 and 500 microm, an angle of repose smaller than 36 degrees and a granule yield above 90%. Moreover, the values of the tensile strength of the tablets should be between 1.6 and 2.5 N/mm2. The intersections of the response surfaces of each examined substance were compared using contour plots. To achieve the largest "satisfactory zone," the granulations of milled alpha-lactose-monohydrate, dicalcium phosphate, or potato starch should be performed at low inlet air temperatures.     

Effects of process parameters on solid self-microemulsifying particles in a laboratory scale fluid bed

The purpose of this study was to select the critical process parameters of the fluid bed processes impacting the quality attribute of a solid self-microemulsifying (SME) system of albendazole (ABZ). A fractional factorial design (2(4-1)) with four parameters (spray rate, inlet air temperature, inlet air flow, and atomization air pressure) was created by MINITAB software. Batches were manufactured in a laboratory top-spray fluid bed at 625-g scale. Loss on drying (LOD) samples were taken throughout each batch to build the entire moisture profiles. All dried granulation were sieved using mesh 20 and analyzed for particle size distribution (PSD), morphology, density, and flow. It was found that as spray rate increased, sauter-mean diameter (D(s)) also increased. The effect of inlet air temperature on the peak moisture which is directly related to the mean particle size was found to be significant. There were two-way interactions between studied process parameters. The main effects of inlet air flow rate and atomization air pressure could not be found as the data were inconclusive. The partial least square (PLS) regression model was found significant (P < 0.01) and predictive for optimization. This study established a design space for the parameters for solid SME manufacturing process.     

Enhancing tablet disintegration characteristics of a highly water-soluble high-drug-loading formulation by granulation process

Abstract

The objective of this study was to improve the disintegration and dissolution characteristics of a highly water-soluble tablet matrix by altering the manufacturing process. A high disintegration time along with high dependence of the disintegration time on tablet hardness was observed for a high drug loading (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process. Keeping the formulation composition mostly constant, a fluid-bed granulation (FBG) process was explored as an alternate granulation method using a 2^(4?1) fractional factorial design with two center points. FBG batches (10 batches) were manufactured using varying disingtegrant amount, spray rate, inlet temperature (T) and atomization air pressure. The resultant final blend particle size was affected significantly by spray rate (p?=?.0009), inlet T (p?=?.0062), atomization air pressure (p?=?.0134) and the interaction effect between inlet T*spray rate (p?=?.0241). The compactibility of the final blend was affected significantly by disintegrant amount (p?<?.0001), atomization air pressure (p?=?.0013) and spray rate (p?=?.05). It was observed that the fluid-bed batches gave significantly lower disintegration times than the HSWG batches, and mercury intrusion porosimetry data revealed that this was caused by the higher internal pore structure of tablets manufactured using the FBG batches.     

Understanding and predicting bed humidity in fluidized bed granulation

Bed humidity is a critical parameter that needs to be controlled in a fluidized bed granulation to ensure reliability. To predict and control the bed humidity during the fluidized bed granulation process, a simple model based on the mass conservation of moisture was developed. The moisture mass balance model quantitatively simulates the effects of spray rate, binder solution concentration, airflow rate, inlet air temperature, and dew point on the bed humidity. The model was validated by a series of granulations performed in different scale granulators including Glatt GPCG-1, GPCG-15, and GPCG-60. Good agreement was observed between the theoretical prediction and the measured loss on drying (LOD). The model developed in the current work enables us to choose the appropriate parameters for the fluidized bed granulation and can be used as a valuable tool in process scaling-up.     

Integrated optimization of fish oil microencapsulation process by spray drying

An integrated approach through coupling response surface method (RSM) and genetic algorithm (GA) was applied to optimize the spray dryer operational condition for production of fish oil microcapsules. The inlet drying air temperature, aspirator rate, and peristaltic pump rate were independent and encapsulation efficiency (EE) and exergy efficiency were dependent variables. RSM was applied to establish the relationship between the independent and dependent variables followed by integrating the developed models using three mathematical approaches and measure the fitness value of GA. Consequently, the optimal drying condition for microencapsulation of fish oil was: inlet drying air temperature?=?177.23°C, aspirator rate?=?63.93%, and peristaltic pump rate?=?14.04% yielding exergy efficiency of 8.10% and EE of 79.14%. The results of confirmation experiments for selected drying condition proved the capability of utilized approach for determination of sustainable and qualified process in fish oil microencapsulation by spray drying.     

Evaluation and simultaneous optimization of some pellets characteristics using a 3(3) factorial design and the desirability function

A 3(3) full factorial design study has been employed in order to investigate the effect of three variables on size, size distribution and three shape parameters, namely roundness, elongation and e(R), of pellets prepared in a fluid bed rotor granulator with the wet granulation technique. The first variable was a formulation variable, the % w/w content of microcrystalline cellulose (MCC) and the other two variables were processing variables, the temperature of inlet air and the spray rate of the granulation liquid. The analysis of variance showed that the three variables had a significant effect (P<0.05) on pellet size and the shape factors, while only the spray rate influenced the particle size distribution. Significant interactions between the factors, for the size and the shape, were also found. The multiple regression analysis of the results led to equations that adequately describe the influence of the independent variables on the selected responses. Furthermore, the desirability function was employed in order to optimize the process under study. It was found that the optimum values of the responses could be obtained at the low levels of the % w/w content of MCC and temperature of inlet air and at the high level of the spray rate.     

Effects of process parameters on solid self-microemulsifying particles in a laboratory scale fluid bed

The purpose of this study was to select the critical process parameters of the fluid bed processes impacting the quality attribute of a solid self-microemulsifying (SME) system of albendazole (ABZ). A fractional factorial design (2^4–1) with four parameters (spray rate, inlet air temperature, inlet air flow, and atomization air pressure) was created by MINITAB? software. Batches were manufactured in a laboratory top-spray fluid bed at 625-g scale. Loss on drying (LOD) samples were taken throughout each batch to build the entire moisture profiles. All dried granulation were sieved using mesh 20 and analyzed for particle size distribution (PSD), morphology, density, and flow. It was found that as spray rate increased, sauter-mean diameter (D_s) also increased. The effect of inlet air temperature on the peak moisture which is directly related to the mean particle size was found to be significant. There were two-way interactions between studied process parameters. The main effects of inlet air flow rate and atomization air pressure could not be found as the data were inconclusive. The partial least square (PLS) regression model was found significant (P?<?0.01) and predictive for optimization. This study established a design space for the parameters for solid SME manufacturing process.     

Using experimental design to optimize the process parameters in fluidized bed granulation on a semi-full scale

A face-centered central composite design was applied in order to optimize the granulation process on a semi-full scale (30-kg batch) for the geometric mean granule size. The granulation process variables investigated were: inlet air temperature, inlet airflow rate, spray rate and inlet air humidity. Based on the process variables, the theoretical powder bed moisture content after the spraying process and a measure for the droplet size were determined. Multiple regression modeling was used to develop two models for the granule size: an empirical model, based on the four process parameters, and a fundamental model, based on the balance between the granule growth affected by the theoretical powder bed moisture content and the droplet size and the breakage effect of the airflow rate. These regression models were used to optimize the granulation process to obtain a granule size between 300 and 500 μm. Additional experiments confirmed that these models were valid. Other granule properties, namely the geometric standard deviation, the Hausner index, the angle of repose and the moisture content, were evaluated at the optimal operation conditions.