Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine / 中国中药杂志

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

Research on batch-to-batch quality control of compound Danshen extract based on physical characterization and multivariate statistical analysis / 中国中药杂志

Physical attributes of Chinese herbal extracts are determined by their chemical components, and the physical and chemical attributes jointly affect the preparation process performance and the final product quality. Therefore, in order to improve the quality control of Chinese herbal extracts, we should comprehensively study the batch-to-batch consistency of physical and chemical attributes as well as the correlations between them. This paper first explored the physical attributes affecting the preparation process performance of the compound Danshen extract and developed a method for characterizing the texture attributes. With such main chemical components as water, phenolic acids, saponins, and saccharides and texture, rheology, and other physical attributes taken into consideration, the batch-to-batch quality fluctuation of products from different production lines and time was analyzed by principal components analysis(PCA). Finally, the correlation and partial least squares(PLS) analysis was conducted, and the regression equation was established. The fitting result of the PLS model for dynamic viscosity was satisfying(R~2Y=0.857, Q~2=0.793), suggesting that the chemical components could be adjusted by the component transfer rate in the extraction process, the impurity removal rate in the alcohol precipitation process, and the water retention rate of the concentration process to meet the control of the extract dynamic viscosity. This study clarified the correlations between physical and chemical attributes of the compound Danshen extract and established a method for controlling its physical attributes based on process regulation, which would provide reference for improving the quality control of Chinese herbal extracts.

Spray Drying in Research of Traditional Chinese Medicine Powders： A Review / 中国实验方剂学杂志

After more than 100 years of development， spray drying technology has become more mature and widely used， and it is of great importance in the field of traditional Chinese medicine （TCM）. TCM powders prepared by spray drying is the raw material of dispensing granules， and the powder properties have an important influence on subsequent molding process and product quality. As a new form of TCM， dispensing granules have been included in the management category of TCM decoction pieces， indicating a broader application market， and a consensus has also been reached on the importance of TCM powder research. Based on this， the author summarized the application progress of spray drying in the study of TCM powders， including the factors affecting spray drying process， such as liquid properties， process parameters and equipment factors， as well as the application of computational fluid dynamics （CFD） and thermodynamic model in spray drying process simulation. Moreover， some commonly used pharmaceutical excipients for the modification of TCM powders were also introduced such as maltodextrin， microcrystalline cellulose and povidone. In addition， spray drying technology can also be used as a preparation technology for new drug delivery systems such as microcapsules and solid dispersions. Through the summary of this paper， the author suggests that the future research direction of spray drying of TCM can be carried out from the aspects of application rule of the coprocessing auxiliary materials based on the "unification of medicines and excipients"， the "structure-property" relationship of spray-dried powders and the application of computer simulation and design， so as to further enrich the application of spray drying in the field of TCM powders.

Mechanism of "unification of drugs and excipients" for Chinese medicine semi-extract based on powder compression behavior analysis / 中国中药杂志

In this paper, five representative Chinese herbal decoction pieces of Scutellariae Radix, Paeoniae Radix Alba, vinegar-processed Corydalis Rhizoma, Polygoni Multiflori Radix Praeparata and Lonicerae Japonicae Flos were selected to prepare the corresponding fine powder of pieces, extract powder, semi-extract powder and physical mixed powder. The physical properties of 20 kinds of powders, such as related parameters of particle size, density, stability and flowability, were evaluated comprehensively. The compression curves of powder porosity and tensile strength changing with pressure were plotted, and the Heckel equation and the Kawakita equation were used to describe the powder compression behavior. The results showed that compared with the fine powder of pieces, the compressibility of the semi-extract powder and the extract powder was significantly improved. Compared with the extract powder, the particle size and relative uniformity of the semi-extract powder were increased, indicating that the uniformity of the powder was improved. Besides, the semi-extract powder could reduce the hygroscopicity of the powder. Particularly, the semi-extract powder of Scutellariae Radix, Paeoniae Radix Alba and vinegar-processed Corydalis Rhizoma could maintain the porous structure of the tablet even under a high tableting pressure, which was beneficial to tablet disintegration. For some traditional Chinese medicines(such as Lonicerae Japonicae Flos), the semi-extract powder could reduce the viscosity, which avoided the sticking in the die compression. The semi-extract powder and the physical mixture powder prepared by the same Chinese herbal decoction pieces had similar physical properties and compression behaviors. Principal component analysis(PCA) was carried out on the 17 physical attributes and 5 compression parameters of the powder. It was found that the first principal component mainly reflected the differences among the material sources, while the second principal component could reflect the differences among fine powder of pieces, extract powder, semi-extract powder and physical mixed powder originating from the same Chinese herbal decoction pieces. In this paper, the mechanism of "unification of drugs and excipients" of Chinese medicine semi-extract powder was explained in terms of physical properties and compression behavior of powders, which provided reference for the formulation design and process development of Chinese medicine tablets.

Physical characterization of multiparticulate systems

ABSTRACT The search for new pharmaceutical dosage forms and different drug delivery systems already used in therapeutics is a global trend, serving as an opportunity to expand the portfolio for the pharmaceutical industry. In this context, multiparticulate systems, such as pellets, granules, and minitablets, represent an attractive alternative, given the range of possibilities they provide. Among the methods used in the production of these systems, we highlight the process of extrusion-spheronization for pellet manufacture, wet granulation and hot-melt extrusion for the obtention of granules, and direct compression for minitablets. Although highly versatile, depending on the technology chosen, many processes and formulation variables can influence the ensuing stages of manufacture, as well as the final product. Therefore, the characterization of these small units is of fundamental importance for achieving batch homogeneity and optimal product performance. Analyses, including particle size distribution, morphology, density, porosity, mechanical strength and disintegration, are example tests used in this characterization. The objective of this review was to address the most widely used tests for the physical evaluation of multiparticulate systems.

Comprehensive Evaluation of Powdered Chinese Herbal Medicines-An Exemplification of Isatidis Radix / 中草药·英文版

Objective Currently, powdered Chinese herbal medicines (CHMs) were mainly evaluated through physical property, chemical dissolution, and bioactivity independently. It could not reflect the quality comprehensively. This paper was to explore and establish a comprehensive evaluation method for powdered CHMs. Methods Isatidis Radix was chosen as an exemple. Firstly, powdered Isatidis Radix in different particle size was prepared. Then, their physical properties were characterized. The dissolution of index component epigoitrin was determined, and their antiviral activities were evaluated by neuraminidase-based bioassay. Results As the particle size decreased, powder distribution tended to be uniform, and the dissolution of epigoitrin increased, antiviral activity enhanced. According to cluster analysis of above results, the sequence of evaluation consequence was ultrafine powder S2 (D90: 32.80 ± 0.29) > ultrafine powder S1 (D90: 52.08 ± 0.53) > fine powder S0 (D90: 118.16 ± 0.76) (from the superior to the inferior). Conclusion Overall, the comprehensive evaluation for powdered CHMs based on the physical characterization, chemical dissolution, and bioassay could not only be used to evaluate powdered herbs, but also guide the screening and optimization of the particle size of powder.

Caracterização e classificação dos resíduos de construção civil da cidade de Fortaleza (CE) / Characterization and classification of construction waste in Fortaleza (CE)

Este estudo visa analisar a composição gravimétrica, avaliar parâmetros químicos e classificar os Resíduos de Construção Civil (RCC) da cidade de Fortaleza de acordo com a Resolução CONAMA nº 307 e com a NBR 10004. Os resultados indicam que o RCC de Fortaleza é composto por 93,40% do Grupo A, 6,40% do Grupo B, 0,02% do Grupo C e 0,20% Grupo D. O primeiro é composto principalmente por areia e solo (24,65%) e argamassa (22,00%), que são materiais com alto potencial de reutilização ou reciclagem. Além disso, de acordo com a análise química, o RCC de Fortaleza mostrou alta variabilidade em todos os parâmetros. Cr, Pb e SO4²-, por exemplo, apresentaram valores acima dos limites especificados pela NBR 10004, indicando que esse material deve ser classificado como Classe II-A (não perigoso e não inerte).

This study aims to analyze the gravimetric composition, evaluate chemical parameters and classify the construction waste (CW) of Fortaleza city according to CONAMA Resolution Nº 307 and to NBR 10004. Results show that Fortaleza's CW is composed by 93,40% of Group A, 6,40% Group B, 0,02% Group C and 0,2% Group D. The first is composed primarily by sand and gravel (24,65%) and mortar (22,00%), that are materials with high potential for reuse or recycling. Moreover, according to chemical analysis, Fortaleza's CW showed a high variability in all parameters. Cr, Pb and SO4²-, for example, showed above to the limits specified by NBR 10004, indicating that this material have to be classified as Class II-A (not dangerous and not inert).

Análise de frutos e nozes de cultivares de nogueira-macadâmia / Analysis of fruits and nuts of macadamia walnut cultivars

A produção da nogueira-macadâmia é quantificada em "noz em casca" (casca e amêndoa). Assim, cultivares que possuam maior calibre detêm maior valor comercial. Sendo assim, o objetivo do presente trabalho foi realizar a análise de frutos e nozes de 22 cultivares de nogueira-macadâmia. As cultivares utilizados foram: 'África', 'Beaumont' (695), 'Cannon', 'C160', 'Doroti', 'Edson', 'Flor Rosa', 'HAES 722', 'HAES 814', 'HAES 816', 'HAES 842', 'HAES 849', 'IAC Campinas-B', 'IAC 9-20', 'IAC 9-20X', 'IAC 4-12B', 'Kau' ('HAES 344'), 'Keauhou' ('HAES 246'), 'Keaumi' ('IAC 4-20'), 'Mauka' ('HAES 741'), 'Pahala' ('HAES 788') e '791 Fuji'. Foram determinadas as dimensões (comprimento e diâmetro) e a massa fresca do carpelo, casca e amêndoa, além da massa fresca da "noz em casca" (casca e amêndoa), do TR (relação entre a massa das nozes em casca e a massa das amêndoas resgatadas). As cultivares apresentam diferenças quanto as dimensões dos frutos. A cultivar 'Edson' apresentou frutos e nozes com maiores dimensões e massa. Apenas as cultivares 'Pahala', 'Beaumont', 'IAC 9-20X' e 'Keaumi' apresentaram TR menor que 30 por cento.

The production of the macadamia walnut is measured in "nut in peel" (peel and almond). The cultivar that have higher caliber has greater commercial value. The objective of the present research was to analysis of fruits and nuts of 22 cultivars of macadamia walnut. The cultivars used were: 'África', 'Beaumont' (695), 'Cannon', 'C160', 'Doroti', 'Edson', 'Flor Rosa', 'HAES 722', 'HAES 814', 'HAES 816', 'HAES 842', 'HAES 849', 'IAC Campinas-B', 'IAC 9-20', 'IAC 9-20X', 'IAC 4-12B', 'Kau' ('HAES 344'), 'Keauhou' ('HAES 246'), 'Keaumi' ('IAC 4-20'), 'Mauka' ('HAES 741'), 'Pahala' ('HAES 788') and '791 Fuji'. It was determined the dimensions (length and diameter) and the fresh weight of the carpelo, peel and almond, besides the fresh weight of the "nut in peel" (peel and almond), besides TR (relationship among the weight of the nut in peel and the weight of the rescued almonds). The cultivars presented differences as the dimensions of the fruits. The cultivar 'Edson' presented fruits and nuts with larger dimensions and weight. The cultivars 'Pahala', 'Beaumont', 'IAC 9-20X' and 'Keaumi' presented TR lower than 30 percent.

Caracterização de lavouras cafeeiras, utilizando técnicas de geoprocessamento e sensoriamento remoto, no município de Umuarama - PR / Characterization of coffee crops using techniques of geoprocessing and remote sensing in the city of Umuarama - PR

O sensoriamento remoto e o geoprocessamento são geotecnologias importantes no apoio ao levantamento de dados da agricultura, permitindo estudos e o entendimento das relações ambientais em que uma determinada cultura está inserida. Neste trabalho,objetivou-se, relacionar as variáveis físicas, como, altimetria, declividade e tipo de solo com o agrossistema cafeeiro existente no município de Umuarama-PR pelo uso de geotecnologias. Foi utilizada a imagem do satélite LANDSAT 5/TM (Thematic Mapper) com data de passagem em 02/07/2007 e o software SPRING 4.3.3. As bandas 3, 4 e 5 do sensor TM foram restauradas, resultando em imagens de 15 m de resolução espacial e, posteriormente, constituindo a composição colorida RGB, na sequência TM4, TM5, TM3, a qual foi empregada na identificação das lavouras cafeeiras por meio de interpretação visual. Para o estudo do relevo, foram utilizados dados da missão SRTM, os quais possibilitaram o conhecimento da altimetria e declividade da região. A imagem do sensor TM possibilitou a execução da classificação visual e consequente identificação das lavouras cafeeiras com alta precisão. Quanto ao relevo, verificou-se que aproximadamente 99 por cento das lavouras cafeeiras estão localizadas entre 380 e 480 metros de altitude e que 90 por cento destas estão situadas em declividades de até 8 por cento de inclinação. Em relação aos solos, observou-se que 89 por cento dos cafeeiros são cultivados sobre Latossolo Vermelho distrófico, de textura arenosa.

The remote sensing and geoprocessing are important geotechnologies in support of the survey data of agriculture, enabling studies and understanding of environmental relations in which a particular culture is insert. The objective of this work was to relate the physical variables, such as altimetry, slope and soil type with the coffee agrosystems in Umuarama-PR through the geotechnologies. The image of the LANDSAT 5/TM (Thematic Mapper) dated in 02/07/2007 and the software SPRING 4.3.3 were used for the image processing. The bands 3, 4 and 5 of the sensor TM were restored, which resulted in images of 15m spatial resolution and, later, creating the RGB color composition, which was used to identify the coffee crops through visual interpretation. For the relief map study, the data of the SRTM mission were applied, which enabled us to know the altimetry and declivity of the region. The image of the TM sensor enabled the visual classification and the consequent identification of the coffee crops with high precision. As for the relief area, it was noticed that about 99 percent of the coffee fields are located between 380 and 480 meters of altitude and that 90 percent of them are located in declivity of up to 8 percent of inclination. About the soils, it was observed that 89 percent of the coffee fields are grown over distrofic Red Latosol, of sandy texture.