人工鼻和气体流量设置对气道内吸入气温度和湿度的影响

目的：观察麻醉机呼吸环路气体低、中、高流量设置和呼吸环路加入人工界对气道内吸入气温度和湿度的影响。方法：选择60名ASA I～Ⅱ级病人，随机分为6组，3组呼吸环路内加入人工界，流量设置分别是0，5，1．5，4．5L/min；另3组不使用人工界，流量设置同上。应用温度湿度仪连续监测吸入气温度和相对湿度，公式计算绝对温度。机械通气3min后的测量值设为基础值，然后纪录15，30，45和60min的值。结果：随机械通气时间延长，人工鼻组的不同流量设置均显著增加气道内吸入气温度和湿度，当流量设置为0．5L/min最高，其次是1．5L/min，再其次为4．5L/min；不用人工鼻组，低、中、高流量设置显著影响气道内吸入气温度和湿度，随通气时间延长，流量为0．5L/min时温度和湿度逐渐升高，1．5L/min略有下降，4．5L/min则明显降低。结论：人工界能补偿气体中、高流量时气道内温度和湿度的降低，低流量增加气道内的温度和湿度。临床采用低流量麻醉技术和人工界对保护病人气道粘膜有利。     

Suitability of near-infrared methods for the determination of moisture in a freeze-dried injection product containing different amounts of the active ingredient

A near-infrared reflectance (NIR) method for determination of moisture in an experimental freeze-dried injection product was developed and validated. NIR spectra were collected through the bases of unopened product vials using a horizontal instrument accessory, before generating primary reference data on the same individual vials by Karl-Fischer titration. Data were collected for product containing different concentrations of the active ingredient in the same matrix. NIR calibrations were developed with second derivative spectral data using regression facilities within the NIR software, and validated using independent test sets. An assessment is given of the applicability of moisture calibrations developed on product at one active ingredient level to the prediction of moisture contents in the product containing a different concentration of active ingredient.     

Effect of Spray Drying and Subsequent Processing Conditions on Residual Moisture Content and Physical/Biochemical Stability of Protein Inhalation Powders

Purpose. To understand the effect of spray drying and powder processing environments on the residual moisture content and aerosol performance of inhalation protein powders. Also, the long-term effect of storage conditions on the powder's physical and biochemical stability was presented. Methods. Excipient-free as well as mannitol-formulated powders of a humanized monoclonal antibody (anti-IgE) and recombinant human deoxyribonuclease (rhDNase) were prepared using a Buchi 190 model spray dryer. Residual moisture content and moisture uptake behavior of the powder were measured using thermal gravimetric analysis and gravimetric moisture sorption isotherm, respectively. Protein aggregation, the primary degradation product observed upon storage, was determined by size-exclusion HPLC. Aerosol performance of the dry powders was evaluated after blending with lactose carriers using a multi-stage liquid impinger (MSLI). Results. Spray-dried powders with a moisture level (~ 3%) equivalent to the freeze-dried materials could only be achieved using high-temperature spray-drying conditions, which were not favorable to large-male manufacturing, or subsequent vacuum drying. These dry powders would equilibrate with the subsequent processing and storage environments regardless of the manufacturing condition. As long as the relative humidity of air during processing and storage was lower than 50%, powders maintained their aerosol performance (fine particle fraction). However, powders stored under drier conditions exhibited better long-term protein biochemical stability. Conclusions. Manufacturing, powder processing, and storage environments affected powder's residual moisture level in a reversible fashion. Therefore, the storage condition determined powder's overall stability, but residual moisture had a greater impact on protein chemical stability than on powder physical stability.     

眩晕定颗粒的吸湿性研究

目的:研究眩晕定颗粒的吸湿性,确定眩晕定颗粒生产过程中合理的湿度条件及暴露时间。方法:通过测定眩晕定颗粒的吸湿速度及平衡吸湿量,建立其动力学模型,提取吸湿速度参数并比较大小。结果:眩晕定颗粒在不同湿度下的吸湿动力学符合房室模型,吸湿量达到6%对应的相对湿度为56.11%,在此湿度下包装前最久可摆放10.15h。结论:眩晕定颗粒生产中应控制环境湿度在56%以下,分装时暴露时间不可超过10.15h。     

The Nonsteady State Modeling of Freeze Drying: In-Process Product Temperature and Moisture Content Mapping and Pharmaceutical Product Quality Applications

Introduction. Theoretical models of the freeze-drying process are potentially useful to guide the design of a freeze-drying process as well as to obtain information not readily accessible by direct experimentation, such as moisture distribution and glass transition temperature, T_g, within a vial during processing. Previous models were either restricted to the steady state and/or to one-dimensional problems. While such models are useful, the restrictions seriously limit applications of the theory. An earlier work from these laboratories presented a nonsteady state, two-dimensional model (which becomes a three-dimensional model with an axis of symmetry) of sublimation and desorption that is quite versatile and allows the user to investigate a wide variety of heat and mass transfer problems in both primary and secondary drying. The earlier treatment focused on the mathematical details of the finite element formulation of the problem and on validation of the calculations. The objective of the current study is to provide the physical rational for the choice of boundary conditions, to validate the model by comparison of calculated results with experimental data, and to discuss several representative pharmaceutical applications. To validate the model and evaluate its utility in studying distribution of moisture and glass transition temperature in a representative product, calculations for a sucrose-based formulation were performed, and selected results were compared with experimental data. Theoretical Model. The model is based on a set of coupled differential equations resulting from constraints imposed by conservation of energy and mass, where numerical results are obtained using finite element analysis. Use of the model proceeds via a “modular software package” supported by Technalysis Inc. (Passage?/Freeze Drying). This package allows the user to define the problem by inputing shelf temperature, chamber pressure, container properties, product properties, and numerical analysis parameters required for the finite element analysis. Most input data are either available in the literature or may be easily estimated. Product resistance to water vapor flow, mass transfer coefficients describing secondary drying, and container heat transfer coefficients must normally be measured. Each element (i.e., each small subsystem of the product) may be assigned different values of product resistance to accurately describe the nonlinear resistance behavior often shown by real products. During primary drying, the chamber pressure and shelf temperature may be varied in steps. During secondary drying, the change in gas composition from pure water to mostly inert gas is calculated by the model from the instantaneous water vapor flux and the input pumping capacity of the freeze dryer. Results. Comparison of the theoretical results with the experiment data for a 3% sucrose formulation is generally satisfactory. Primary drying times agree within two hours, and the product temperature vs. time curves in primary drying agree within about ± 1°C. The residual moisture vs. time curve is predicted by the theory within the likely experimental error, and the lack of large variation in moisture within the vial (i.e., top vs. side vs. bottom) is also correctly predicted by theory. The theoretical calculations also provide the time variation of “T_g–T” during both primary and secondary drying, where T is product temperature and T_g is the glass transition temperature of the product phase. The calculations demonstrate that with a secondary drying protocol using a rapid ramp of shelf temperature, the product temperature does rise above Tg during early secondary drying, perhaps being a factor in the phenomenon known as “cake shrinkage”. Conclusion. The theoretical results of in-process product temperature, primary drying time, and moisture content mapping and history are consistent with the experimental results, suggesting the theoretical model should be useful in process development and “trouble-shooting” applications.     

正交实验法优选肿痛消颗粒的成型工艺

目的：通过正交实验优选肿痛消颗粒的成型工艺。方法：以吸湿率为指标考察所用辅料的种类及配比;以吸湿率和成型率指标优选肿痛消颗粒的最佳成型工艺条件,并考察该颗粒的休止角、吸湿率。结果：辅料蔗糖粉/糊精以2∶1为最好;浸膏与辅料的混匀比例为1∶1,润湿剂体积分数为60%,干燥温度为60℃,依此制得的颗粒流动性好。结论：本成型工艺合理、可行,可为该颗粒的大量生产提供科学依据。     

人工鼻对人工气道患者下呼吸道医院感染扩散拦截作用的研究

目的研究人工鼻对人工气道患者下呼吸道医院感染扩散的拦截作用效果。方法通过使用人工鼻前后医院感染发生率的比较和同一人工鼻不同拦截面的菌株数比较,研究人工鼻对医院感染细菌扩散的拦截作用。结果使用人工鼻前后医院感染发生率和同一人工鼻不同拦截面的菌株数比较,差异均有统计学意义。结论人工鼻对人工气道患者下呼吸道医院感染扩散的拦截作用明显,具有预防医院感染扩散的作用。     

温度对 3 种中药浸膏片包衣工艺参数的影 响简

目的 研究温度对3种中药浸膏片包衣工艺的影响.方法 将素片置恒湿变温环境中,不同时间称定片重,记录、计算吸湿增重,分析吸湿数据;将素片置干燥环境中,其余条件相同情况下,记录、计算减重百分率、绘制减重速率曲线图.结果 冠心平片和健肾片的吸湿速率随温度升高而降低,而保肾片的吸湿速率随温度升高而升高;保肾片和冠心平片在60℃的减重百分率大于50℃的减重百分率,而健肾片的减重百分率在50℃和60℃之间变化不明显.结论 吸湿性参数、干燥速率参数可为包衣工艺参数的制订提供科学数据.     

近红外光谱用于甘草中甘草苷、甘草酸及水分测定

目的:运用近红外光谱(NIR)技术检测甘草药材中的甘草苷、甘草酸及水分。方法:采用积分球漫反射扫描近红外光谱,以TQ Analyst软件进行数据分析,建立甘草中甘草苷、甘草酸及水分测定的NIR。结果:甘草苷的预测均方根误差(RMSEP)为0.165,预测集相关系数(Rp)0.986 8;交叉验证均方根误差(RMSECV)为0.393,校正集相关系数(Rv)0.904 6。甘草酸的RMSEP=0.166,Rp=0.995 5;RMSECV=0.575,Rv=0.954 0。水分的RMSEP=0.137,Rp=0.995 2;RMSECV=0.498,Rv=0.931 9。结论:该方法快速、简便。可以用于甘草中甘草苷、甘草酸及水分的含量测定。