Micronized drug powders in binary mixtures and the effect of physical properties on aerosolization from combination drug dry powder inhalers

Objectives: To evaluate physicochemical properties of two micronized drugs, salbutamol sulfate (SS) and beclomethasone dipropionate (BDP) prepared as dry powder inhalation physical blends. Methods: Five different blends of SS:BDP ratios of 0:100, 25:75, 50:50, 75:25, and 100:0 (w/w) were prepared. Aerosolization performance was evaluated using a multistage impinger and a Rotahaler® device. Results: The median SS particle diameter was larger than BDP (4.33?±?0.37 µm compared to 2.99?±?0.15 µm, respectively). The SS appeared to have a ribbon-like morphology, while BDP particles had plate-like shape with higher cohesion than SS. This was reflected in the aerosolization performance of the two drugs alone, where SS had a significantly higher fine particle fraction (FPF) than BDP (12.3%, 3.1% and 2.9%, 0.2%, respectively). The study of cohesion versus adhesion for a series of SS and BDP probes on SS and BDP substrates suggested both to be moderately adhesive, verified using scanning Raman microscopy, where a physical association between the two was observed. A plot of loaded versus emitted dose indicated that powder bed fluidization was significantly different when the drugs were tested individually. Furthermore, the FPF of the two drugs from the binary blends, at all three ratios, were similar. Conclusions: Such observations indicate that when these two drugs are formulated as a binary system, the resulting powder structure is altered and the aerosolization performance of each drug is not reflective of the individual drug performance. Such factors could have important implications and should be considered when developing combination dry powder inhalation systems.     

用于快速检测沙丁胺醇的分子印迹传感器的制备及其在食品检测中的应用

首先通过电沉积纳米金,电聚合聚硫堇对玻碳电极表面进行了修饰,之后利用沙丁胺醇为模板分子,通过电聚合α-甲基丙烯酸,制备了一种选择性具有特异识别功能的纳米金/聚硫堇/沙丁胺醇分子印迹电化学传感器。实验采用循环伏安法和差分脉冲法,对不同的修饰电极进行了表征,优化电极的制备和测定条件,研究了印迹传感器对模板分子的选择性响应。结果表明:最佳制备条件下,模板分子:功能单体=1:4,聚合15圈,以0.5 mmol/L硫酸:乙腈(1:9,V/V)洗脱10 min,在pH=7.0的PBS溶液中进行DPV检测,线性范围为2.0×10~(-7)~1.0×10~(-4) mol/L,检测限为6.0×10~(-8) mol/L,S/N=3。该传感器灵敏度高,抗干扰能力强,重现和稳定性好。利用制备的分子印迹电化学传感器对食品中的沙丁胺醇进行了测定,回收率在86.5%~111.9%(n=3),结果令人满意。     

Kinetics of emitted mass—A study with three dry powder inhaler devices

The purpose of this study was to understand the kinetics of emptying of micronised salbutamol sulphate (SS) and lactohale 300 (LH300) under varying air flow rates (30–180 L min⁻¹) from three dry powder inhaler devices, Rotahaler^® (RH), Monodose Inhaler^® (MI) and Handihaler^® (HH). Aerosol concentration vs. time profiles, determined through real-time laser diffraction particle sizing, demonstrated that the majority of the powder from RH was emitted within one second while a more prolonged aerosolisation was observed from MI and HH. Peak aerosol concentrations were achieved more rapidly from RH compared to MI for both SS and LH300. Calculated cumulative emitted mass (CCEM) vs. time profiles were obtained from the aerosol concentration vs. time profiles and the emitted mass and the rate of CCEM (k_CCEM), estimated from a modelling approach, increased with increasing air flow rates. The k_CCEMvs. air flow rate profiles of SS and LH300 were significantly different at high air flow rates. The k_CCEM was highest from RH and lowest from MI. Differences in k_CCEM between the devices were related to capsule aperture size while the differences between the materials were due to the powder bed structure. This approach provided an understanding of the rate at which powder mass emptied from dry powder inhaler devices and was proposed to be a powerful development tool for the future powder inhalers.     

肉制品中瘦肉精药物残留检测方法的简化研究

研究、探讨一种简化样品前处理过程的肉制品中克伦特罗、莱克多巴胺、沙丁胺醇药物残留的检测方法。与国家标准GB/T 22286-2008《动物源性食品中多种β-受体激动剂残留量的测定液相色谱串联质谱法》相比,该方法选取添加高浓度(70%~72%)高氯酸对酶解样品进行直接提取和沉淀蛋白,而后通过固相萃取净化,上机检验;省去了较为繁杂的调溶液pH,液液萃取等实验步骤,提高了整个过程的检验效率。通过对该方法检验结果的准确性、精密度、检出限的验证和评价,结果均符合国家标准对检验方法的要求。该方法可以尝试作为实验室肉制品中3种β2-受体激动药物残留的筛查,甚至检验的参考方法。     

Swelling,erosion and drug release characteristics of salbutamol sulfate from hydroxypropyl methylcellulose-based matrix tablets

Background: Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Method: Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. Results: The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. Conclusion: The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.     

一种检测沙丁胺醇的高灵敏复合纳米免疫电化学传感器的研制

制备一种新型纳米金-石墨烯修饰的复合纳米免疫传感器,并对电极表面修饰材料进行了表征;应用循环伏安法研究沙丁胺醇在修饰电极表面的电化学行为,用差分脉冲伏安法对其检测范围进行实验研究。结果表明：差分脉冲伏安法所得电流差与沙丁胺醇质量浓度在1×10－6～5×10－3 g/L内呈良好的线性关系,检测限为2×10－7 g/L,对牛肉、鸭肉、猪肉和猪肝中的沙丁胺醇含量分别进行测定,平均回收率在91.2%～102.2%之间,结果令人满意。复合纳米免疫传感器具有良好的稳定性和重复性。     

硫酸沙丁胺醇脉冲缓释片的制备

目的探讨制备硫酸沙丁胺醇脉冲缓释片的方法。方法用粉末直接压片法制备片心,干压包衣技术制备脉冲缓释片。正交试验优选处方,对最优处方进行体外释放度验证。结果脉冲缓释片迟滞时间为2￣3h,迟滞后药物释放符合Higuchi方程。结论硫酸沙丁胺醇脉冲缓释片处方设计和工艺方法可行,质量稳定。     

抗3种β-激动剂双特异性单克隆抗体的建立及鉴定

制备抗克仑特罗、沙丁胺醇和莱克多巴胺双特异性抗体并初步鉴定。将分泌抗克仑特罗、沙丁胺醇抗体的细胞株和分泌抗莱克多巴胺抗体的细胞株分别驯化,使之成为HAT敏感株。将两者融合,筛选分泌双特异性单克隆抗体的杂交-杂交瘤株,然后对其进行初步鉴定。共获得5株杂交-杂交瘤细胞株,将其分泌的双特异性单克隆抗体(BsAb)经过酶联免疫吸附法(ELISA)初步检测,IC50可达1 ng/mL,腹水效价为105以上,用ELISA法证明BsAb只与克仑特罗、沙丁胺醇和莱克多巴胺有特异性反应。该方法制备简单、风险低、灵敏度高、周期短,具有较好的应用前景。     

用超声波研究不同温度下4-氨基丁酸在硫酸柳丁氨醇水溶液中的性质(英文)

Ultrasonic speeds of 4-aminobutyric acid in 0.0041,0.0125 and 0.0207 mol·kg-1 aqueous salbutamol sulphate(SBS) solutions are measured at 308.15,313.15 and 318.15 K.Isentropic compressibility kS,change in isentropic compressibility△k S,relative change in isentropic compressibility( 0 S S △k /k) ,apparent molal compressibility kφ,limiting apparent molal compressibility k0 φ,transfer limiting apparent molal compressibility k0 φ,hydration number nH,pair and triplet interaction parameters kAS,kASS are estimated.The above parameters are used to interpret the solute-solute and solute-solvent interactions of 4-aminobutyric acid in the aqueous salbutamol sulphate solutions.     

液相色谱串联质谱内标法测定猪肉中沙丁胺醇及莱克多巴胺残留量的不确定度分析

目的对液相色谱串联质谱内标法测定猪肉中沙丁胺醇、莱克多巴胺2种β-受体激动剂残留量的不确定度进行分析。方法采用液相色谱串联质谱以沙丁胺醇D_3为内标对猪肉中沙丁胺醇、莱克多巴胺2种β-受体激动剂残留量进行测定;建立数学模型,对测量重复性、标准物质纯度、标准溶液配制、内标物质添加、仪器进样体积等不确定因素进行评定。结果当猪肉中沙丁胺醇、莱克多巴胺残留量分别为11.004μg/kg和11.770μg/kg时,其扩展不确定度分别为2.628μg/kg和2.839μg/kg (k=2)。结论标准曲线拟合过程、仪器进样体积、标准系列配制过程对检测结果影响最大。