Research on feedforward control method of mixing process for compound Danshen Dripping Pills based on quality by design(QbD) / 中国中药杂志

The mixing process is one of the key operation units for solid preparation of traditional Chinese medicine. The physical properties such as particle size, density and viscosity of the mixture are key factors that need to be controlled, which will directly affect the performance of the preparation molding process and product quality. Subsequent dripping process performance and appearance qua-lity of dripping pills will be affected by dynamic viscosity of materials in the mixing process. Based on this, with mixing process of compound Danshen dripping pills as the object, a feedforward control method for the dripping pill mixing process was established based on the concept of quality by design(QbD). Firstly, critical quality attribute(CQA)-dynamic viscosity, critical material attributes(CMAs)-the moisture content of compound Danshen extract, average molecular weight of polyethylene glycol 6000 and critical process parameter(CPP)-mixing temperature were identified through the analysis of properties for multiple batches of the raw materials and excipients as well as technological mechanism. Then the Box-Behnken experimental design was used to establish the regression model among CMA, CPP and CMA(R■=0.972 0, RMSE =16.24) to obtain the design space. Finally, through the verification of three batches within the design space, the mixing process temperature was adjusted according to the properties of the raw materials and exci-pients to achieve accurate control of the dynamic viscosity attribute. The relative deviation between the actual dynamic viscosity value and the target value was less than 3.0 %. The feedforward control of the mixing process of compound Danshen dripping pills was rea-lized in this study, which can contribute to improving quality consistency of the mixing process intermediates, simultaneously provide a reference for the research on the process quality control of other Chinese medicine dripping pills.

Changes of polysaccharide content, functional properties and in vitro release of peach gum before and after improvement / 中草药

Objective To analyze the difference of polysaccharides content, property characterization, and in vitro release between the original peach gum and improved peach gum, and to find the change rule, so as to provide the basis for its further application as the new delivery material. Methods The content of polysaccharides was measured by the phenol-sulfuric acid method combined with ultraviolet spectrophotometry. The pH value of liquid cement was measured by pH meter. The dynamic viscosity of liquid cement was measured by the Brookfield DV-Ⅱ Pro viscometer. The solubility and swelling ratio of rubber powder were measured by the weighing method. The moisture-absorption rate at different relative humidity of rubber powder was measured by the method of controlling humidity with the desiccator. With three index components (ephedrine, pseudoephedrine, and scopolamine) as the standards, HPLC and the release test were applied to determine the accumulated release rate of Chuanping adhesive tablets (CAT). Results Original peach gum: In the three producing areas of Xishui in Guizhou Province, Xinfeng in Jiangxi Province, and Suixian in Hubei Province, the content of polysaccharides respectively was 84.30%, 81.52%, and 77.84%. The pH value of 1% liquid cement was 5.63, 5.60, and 5.88. The dynamic viscosity of 1% liquid cement was 30.8, 28.5, and 25.9 mPa∙s. The solubility of rubber powder was 6.08%, 5.75%, and 5.12%. The swelling ratio of rubber powder was 34.22%, 29.66%, and 26.25%. The 12 h moisture-absorption rate of the improved peach gum polysaccharose at RH of 43% was 28.19%, 27.02%, and 26.44%; and at RH of 81% was 38.22%, 35.26%, and 34.64%. The 2 h cumulative release amount in vitro of methamphetamine, pseudoephedrine, and scopolamine of Chuanping adhesive tablets were 95.41%—98.84%, 96.05%—97.11%, and 96.35%—98.21%. Improved peach gum: In the three producing areas of Xishui, Xinfeng, and Suixian, the content of polysaccharides respectively was 96.92%, 94.76%, and 93.35%. The pH of 1% liquid cement was 7.10, 7.08, and 7.12. The dynamic viscosity of 1% liquid cement was 318.4, 289.6, and 266.4 mPa∙s. The solubility of rubber powder was 17.82, 16.73, and 16.38 g. The swelling ratio of rubber powder was 84.98%, 81.55%, and 79.82%. The 12 h moisture-absorption rate of the improved peach gum polysaccharose at RH of 43% was 41.22%, 39.93%, and 39.20%; and at RH of 81% was 60.88%, 58.48%, and 57.17%. The 12 h cumulative release amount in vitro of methamphetamine, pseudoephedrine, and scopolamine of CAT were 97.88%—98.36%, 97.59%—98.56%, and 97.72%—98.12%. Conclusion Compared with the original peach each gum, the content of polysaccharides, dynamic viscosity, solubility, swelling ratio, and moisture-absorption rate, and sustained release property of the improved peach gum were all improved remarkably, and the solution was also neutral. These results show that the improved peach gum can be further developed and applied as a new sustained release material.

Interacciones moleculares de las soluciones acuosas diluidas de nitrato de sodio a partir de datos viscosimétricos / Molecular interactions of aqueous sodium nitrate solutions from viscometric data / Interacções moleculares de soluções aquosas diluídas de nitrato de sódio a partir de dados viscosimétricos

Se determinaron experimentalmente los tiempos de flujo de soluciones NaNO3 + H2O en el intervalo de concentración molal 0,0000-0,9996 (mol/kg). Se usó un microviscosímetro automático Anton Paar®, modelo AMVn, a temperaturas desde 283,15 K hasta 318,15 K cada 5 K y presión atmosférica de 0,101 MPa. A partir de los datos obtenidos, se calcularon las viscosidades dinámicas (η), los coeficientes de viscosidad A , B y C de la ecuación de Jones-Dole, dB/dT y los parámetros de activación del flujo viscoso (ΔG∞‡, ΔH∞‡ y ΔS∞‡) a dilución infinita. Los coeficientes A, B y C resultaron positivos al igual que dBIdT. De acuerdo con el análisis del signo de este último, el NaNO3 actúa como un soluto formador de la estructura del agua. Por otro lado, los parámetros de activación del flujo viscoso a dilución infinita (ΔG∞‡, ΔH∞‡ y ΔS∞‡) revelaron que el proceso de flujo viscoso es endotérmico con un claro predominio de las interacciones ión-solvente.

Flow times of aqueous sodium nitrate solutions in the molal concentration interval 0.0000 to 0.9996 (mol kg) were determined by using an automatic microviscosimeter AMVn Anton Paar® at temperatures ranging from 283.15 K to 318.15 K every 5 K and atmospheric pressure of 0.101 MPa. From the data obtained, the dynamic viscosities (η), the viscosity coefficients A, B, and C form the Jones-Dole equation, dBIdT and the activation parameters of viscous flow (ΔG∞‡, ΔH∞‡ and ΔS∞‡) at infinite dilution were calculated. The coefficients A, B, and C were positive as well as dBIdT. On the one hand, according to the sign analysis, sodium nitrate acts as a structure-forming solute of the water. On the other hand, the activation viscous flow parameters at infinite dilution (ΔG∞‡, ΔH∞‡ y ΔS∞‡) revealed that the viscous flow process is endothermic with a clear ion-solvent interactions predominance.

Foram determinados experimentalmente os tempos de fluxo de soluções NaNO3 + H2O na gama de concentração molal 0,0000-0,9996 (mol/kg). Foi utilização um microviscosímetro automático Anton Paar® modelo AMVn, a temperaturas desde 283,15 K até 318,15 K cada 5 K e à pressão atmosférica de 0,101 MPa. A partir dos dados obtidos foram calculadas as viscosidades dinâmicas (η), os coeficientes de viscosidade A, B, e C da equação Jones-Dole, dB/dT e os parâmetros de ativação de fluxo viscoso (ΔG∞‡, ΔH∞‡ e ΔS∞‡) a diluição infinita. Os coeficientes A, B, e C foram positivos, como dB/dT. De acordo com a análise do signo deste último, o NaNO3 age como um soluto formador da estrutura da água. Além disso, os parâmetros de ativação do fluxo viscoso à diluição infinita (ΔG∞‡, ΔH∞‡ y ΔS∞‡) revelaram que o processo de fluxo viscoso é endotérmico com uma clara predominância de interações íon-solvente.

Determination method of dynamic viscosity of methylcellulose / 中国药学杂志

OBJECTIVE: To solve the existing problems of the determination method of dynamic viscosity of methylcellulose in Chinese Pharmacopoeia (2010 edition): METHODS: By virtue of concentric cylinder rheometer, the experiment probes into the influence of shear rate, temperature measurement, the yield value, thixotropic, etc. on the rheological properties of samples, and identifies then the optimum temperature and shear rate of the samples. RESULTS: The optimum conditions were established as temperature of (20±0.1)°C and shear rate of 80 s-1. CONCLUSION: This method is simple and accurate with good repeatability. It can be applied to determine the viscosity of methylcellulose.