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Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate Cpk integrated Bootstrap-t. The Cpk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.
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Objective: This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine (TCM) and evaluating its biological activity in vitro and binding characteristics. Methods: A combination strategy containing molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation were applied to verify the study result. Results: Gallic acid was confirmed as a direct thrombin inhibitor with IC
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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.
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OBJECTIVE： To prepare pogostone transfersomes， and to evaluate its quality. METHODS： Film dispersion method was used to prepare pogostone transfersomes. Using the accumulative penetration volume （Qn） and accumulative penetration ratio （PR） of pogostone as evaluation indexes， the types of surfactant， formulation were screened in respects of the dosage of surfactant and the dosage of pogostone. The pogostone transfersomes were prepared with optimal formulation； the morphology， particle size distribution and Zeta potential were observed and the entrapment efficiency was measured. RESULTS： The optimal formulation was as follows as the sodium cholate was selected as surfactant； the dosage of sodium cholate was 0.25 g； the dosage of pogostone was 15 mg. The optimal pogostone transfersomes were ivory-white suspension； average particle size was （115.6±3.65） nm （RSD＝3.20％，n＝3）； PDI was 0.185±0.008 （RSD＝4.30％， n＝3）； Zeta potential was （－13.76±0.225） mV （RSD＝1.70％，n＝3）； entrapment efficiency of pogostone was （46.01±0.40）％ （RSD＝0.87％，n＝3）； Qn was （378.76±0.61） μg/cm2 （RSD＝0.20％，n＝3）； PR was （89.02±0.96）％ （RSD＝1.10％，n＝3）. CONCLUSIONS： Prepared pogostone transfersomes are in line with quality requirements， which can provide reference for the further study of new dosage form of pogostone.
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New sensor technologies play an important role in quality evaluation of Chinese materia medica (CMM) and include near-infrared spectroscopy, chemical imaging, electronic nose and electronic tongue. This review on quality evaluation of CMM and the application of the new sensors in this assessment is based on studies from 2010 to 2015, with prospects and opportunities for future research.
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Abstract: The design space of the high shear wet granulation process was established and validated within the framework of quality by design (QbD). The system of microcrystalline cellulose-de-ioned water was used in this study. The median granule size and bulk density of granules were identified as critical quality attributes. Plackeet-Burmann experimental design was used to screen these factors as follows: dry mixing time, the impeller and chopper speed of dry mixing, water amount, water addition time, wet massing time, the impeller and chopper speed of wet massing and drying time. And the optimization was implemented with the central composite experimental design based on screened critical process parameters. The design space of the high shear wet granulation process was established based on the quadratic polynomial regression model. Since the P-values of both models were less than 0.05 and values of lack of fit were more than 0.1, the relationship between critical quality attributes and critical process parameters could be well described by the two models. The reliability of design space, illustrated by overlay plot, was improved with the addition of 95% confidence interval. For those granules whose process parameters were in the design space, the granule size could be controlled within 250 to 355 μm, and the bulk density could be controlled within a range of 0.4 to 0.6 g x cm(-3). The robustness and flexibility of the high shear wet granulation process have been enhanced via the establishment of the design space based on the QbD concept.
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Objective To construct the competitiveness evaluation index system of listed TCM pharmaceutical companies and provide efficient technology and methods for the evaluation in related field.Methods Index base was founded by the means of the literature research method at first. Then 20 experts were asked to score all these indexes according to the importance of each index. Dimensionality and index base of competitiveness evaluation index system of listed TCM pharmaceutical companies were screened. With two rounds of questionnaires, the evaluation index system was constructed finally.Results The positive coefficients of two rounds of expert consultation were 95% and 100%;the cooperative coefficients were 0.659 and 0.639;the authoritative coefficient was 0.713 2. Evaluation system consisted of 5 first grade indexes and 26 second grade indexes.Conclusion The positive coefficients and the authoritative coefficients are both high enough through Delphi method. Opinions of all the experts in the two round of expert consultation tend to be uniform, which reveals that the evaluation index system of listed TCM pharmaceutical companies is relatively scientific.
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Gastrodia elatais graded as top medication in theShen Nong’s Herbal Classic. It was mainly distributed in southwest China. Its quality varied with geographical location. And the quality difference between wild and cultivated sample was extreme. Identifications using traditional methods were unable to accurately distinguish the quality ofG. elata. Therefore, near-infrared (NIR) spectroscopy combined with pattern recognition method was used to distinguish the quality ofG. elata from different geographical locations as well as cultivated or wild. The results demonstrated that using NIR spectroscopy combined with multiclass classification algorithm, the geographical location ofG. elata can be accurately distinguished. The prediction accuracy can reach as high as 94.3% and 96.4% for both applications. Besides, the classification model was built without preprocessing; hence, it can be extended to be applied on-site.
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This study was aimed to optimize the alcohol precipitation techniques for honeysuckle extract in order to standardize the production of honeysuckle extract of Qingkailing Injection and reduce the differences among batches. The orthogonal test was applied in this study. The content of chlorogenic acid and galuteolin were taken as compre-hensive indicators. Multi-index comprehensive scoring method was used in the data analysis. Three influencing fac-tors, which were the fluid temperature, the stirring speed and the speed of adding alcohol, were optimized in the al-cohol precipitation techniques. The results showed that the optimal alcohol precipitation techniques were when the fluid temperature was 20℃, the stirring speed was 240 rpm and the speed of adding alcohol was one time of the ma-terial per minute. It was concluded that the optimized alcohol precipitation process was stable and feasible.
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Objective To establish a method to compare the difference of exposure component of oral taking different part ofPueraria Lobata (Willd.) Ohwi in intestine.Methods After the incubation of puerarin,extraction Radix Puerariae and Flos Puerariae with S9,the mixtures were centrifuged to get the supernatant for analysis with HPLC.Results The research showed that the metabolic rate of puerarin was higher than that of extractions because of the concentration of enzyme.The difference between the fingerprints of Radix Puerariae and Flos Puerariae Lobata indicated that there was a difference of chemical components in such two parts of Kudzuvine Root.Conclusion The profile of intestinal metabolism can be revealed in the research of gut wall metabolism in the course of intestinal absorption by S9 incubation.
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This study was aimed to optimize the near infrared (NIR) variable selection method based on multivariate detection limit (MDL). Using Qing-Kai-Ling (QKL) injection as object, three variable selection methods (interval par-tial least-squares, iPLS; backward interval partial least squares, BiPLS; moving window interval partial least squares, mwPLS) were used to establish the PLS models of baicalin in QKL injection, respectively. The prediction ability of different variable selection method was compared. MDL of all models were calculated in contrast to the MDL value of full spectra PLS model, to select optimal variable selection method. The results showed that different variable selec-tion methods had different prediction ability. Among them, iPLS had the best performance which determination coef-ficient of prediction (Rpre2) and the root mean square errors of prediction (SEP) were 0.996 5 and 602.3 μg·mL-1, re-spectively. All MDLs of different variable selection methods were reduced compared with the full spectra PLS model. The value of iPLS was the lowest comes to be 1.19 μg·mL-1. The results above indicated that the best variable se-lection method for baicalin in QKL injection was iPLS. MDL theory took the error of calibration and validation set and the leverage of external sample into account, which can comprehensively evaluate model detection performance compared to the classic chemical indicator parameters. This method was particularly suitable for the variable selec-tion method optimization of NIR quantitative model of low concentration sample such as Chinese herbal medicine.
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A collection of 57 natural compounds derived from Chinese herbal medicines were evaluated for their an-ti-adipogenic effects. The lipid droplets in differentiated 3T3-L1 adipocytes treated with tested substrate were de-tected by an image-based assay. The results demonstrated that oleanolic acid (OA) inhibited lipid droplets accumula-tion in 3T3-L1 adipocytes in a dose-dependent manner with the IC50 value of 14.5 μmol·L-1. In addition, ToxInsight assay showed that OA was free of liver injury for HepG2 cells within 60 μmol·L-1. It was concluded that OA, which had an obvious anti-adipogenic effect, can be a candidate for hyperlipidemia therapy.
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The literature study and survey revealed existed problems and factors such as the difficulties to maintain quality of traditional Chinese medicine (TCM), sustainable development, homogenization and indeterminacy of clinical orientation diagnosis, lack of favorable evidence-based medicine and pharmacoeconomics data to support, lack of ev-idence of safety evaluation, which restrict the development of TCM enterprises. Based on problems and factors men-tioned above, recommendations were made on the healthy development of TCM enterprises, which include guarantee of the quality of TCM herbs and the sustainable development of its resource; conduct systematic evidence-based pharmacoeconomic research, identify the clinical orientation; carry out safety assessment systematically, improve the specification; improve clinical effectiveness-oriented quality standards.
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ToprovidethemethodologyforrapidqualityevaluationofLonicerajaponica,wehaveestablished the stable quantitative model of near infrared spectroscopy ( NIR) . The performance of Bagging partial least squares (Bagging-PLS) model and Boosting partial least squares (Boosting-PLS) model was compared with that partial least squares ( PLS ) model based on the NIR data of ethanol precipitation process of Lonicera japonica. On this basis, the performance of these two models after variables selection was also studied by the methods of siPLS ( synergy interval partial least squares ) and CARS ( competitive adaptive reweighted sampling) . The experimental results showed that the prediction performance of Bagging-PLS and Boosting-PLS models was superior to PLS model with the latent factor of 10 . The band of 820-1029 . 5 nm and 1030-1239. 5 nm for the first batch was selected by the method of siPLS. In addition, the band of 820-1029. 5 nm and 1030-1239. 5 nm was selected for the second batch sample in the same method. Furthermore, the method of CARS was taken to select variables for the two batches samples with 5-fold cross-validation and 10-fold cross-validation. And the lowest RMSECV( root mean square error of cross-validation) values were used to take subset. Compared to the model performance without the method of CARS, the RMSEP value of the Bagging-PLS model and Boosting-PLS model for the concentration of chlorogenic acid reduced by 0 . 02-0 . 04 g/L and rp(correlation coefficient of prediction)value increased by 4%-5%. Generally, Bagging-PLS and Boosting-PLS could be regarded as rapid prediction methodsfor NIR quantitative models of ethanol precipitation process of Lonicera japonica.
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Laser-induced breakdown spectroscopy (LIBS) was applied to perform qualitative research on Tibetan medicine “GTso Thal” in order to establish a rapid element analysis method . The Nd: YAG laser with the funda-mental frequency at 1064 nm was used. A high-power laser beam was focused on the surface of the sample. The spectrometer and CCD was used to detect its spectrum signals. Based on the National Institute of Standards and Technology (NIST) database, emission spectrum characteristics were differentiated. The LIBS spectra of “GTso Thal”showed multi-elements including Hg, Ca, Na, As, Fe, Mg, Al, K, Li, Pb, Ag, Au and S. Among them, Hg, Pb, Ag and Au were heavy mental elements. The results demonstrated that LIBS was a viable technique for analysis of Ti-betan medicine “GTso Thal”. LIBS provided reliable elemental analysis on Tibetan medicine “GTso Thal”. The de-tection was real-time, rapid and in situ. It had prospects in the elemental analysis of ethnic medicine study. LIBS had broad application prospects.
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This study was aimed to find out the correlation between chemical component contents and physical prop-erties of tanshinone extract powders. The contents of cryptotanshinone and tanshinone IIA from 50 batches of tanshi-none extract powders were determined by HPLC. And the physical properties were determined by classical methods. The correlation analysis between component contents and physical properties were also investigated. The results showed that two sets of variables had good intraclass correlation, especially for the contents of cryptotanshinone and tanshinone IIA, among D10, D50, D90, there were relatively strong correlation between the bulk density and tapped density, between the Hausner ratio and compressibility index. The angle of repose had a certain correlation with the uniformity, Hausner ratio and compressibility index, but with no strong correlation. The correlation coefficient be-tween two sets was below 0.400, suggesting there was a not so good inter-group correlation. After the canonical cor-relation analysis, three pairs of canonical variables had significant correlations with correlation coefficients being 0.851, 0.674 and 0.565, respectively. It was concluded that there was a good intraclass correlation for each of physi-cal and/or chemical quality set, but the correlation between the two sets was bad. Canonical variables performed bet-ter inter-group correlation compared with original variables, indicating there was a certain correlation between chem-ical and physical quality attributes of tanshinone extract powders.
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Near infrared chemical imaging (NIR-CI) is an emerging technology for rapidly analyzing the critical quality attribute of Chinese materia medica (CMM). It integrates NIR spectroscopy with chemical imaging. In this paper, it provided a systematic introduction to NIR-CI, such as the core part of instrument, the reliability, transformation, analysis and application of high-dimensional data acquisition. In addition, current studies of NIR-CI application in pharmaceutical field were analyzed. Finally, future opportunities and challenges of NIR -CI applications in the quality control of CMM preparation were prospected.
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This paper was aimed to discuss the application of content management system (CMS) Drupal in Chinese medicine information fusion. The modular functionality, scalability and strong management capabilities of Drupal can effectively manage and reasonably present information resources of Chinese medicine, which extended the application of Chinese medicine information fusion. Regarding CMS Drupal as the carrier of Chinese medicine information fusion, the Chinese medicine information fusion method can be used in the collection, organization and demonstration of Chinese medicine information in the platform. As one of network tools for Chinese medicine information fusion, Dru-pal will play its powerful function in content management and information publishing with the virtual technology. It will also enrich Chinese medicine information fusion, and promote the spread of Chinese medicine knowledge.
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This study was aimed to establish the classification method of Chinese herbal medicine based on feature parameters extracted from images of herbal transverse section, in order to explore the feasibility of automatic identi-fication method of herbal medicine. The extracted 26 parameters of 18 herbal medicine images by gray-level co-oc-currence matrix and grayscale gradient matrix were used as the basic data set. And the minimum covariance determi-nant (MCD) was used to delete the outliers. A total of 18 identification models were established using the native Bayes method and BP neural network methods. The results showed that the average correct rates of models were 90%. It was concluded the feasibility of using these models in the establishment of the automatic identification method of herbal medicines. It provided new technologies for the quantitative, scientific and objective identification of Chinese herbal medicine.
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This study was aimed to compare the difference of parameters of texture feature in the transverse section images of the same and different Chinese herbal medicine. A total of 26 parameters of herbal medicines were ex-tracted by gray-level co-occurrence matrix and grayscale gradient matrix. The graph of mutative curve was drawn. And differences of 26 parameters of texture feature in the same and different Chinese herbal medicine were com-pared. The results showed that parameters of texture feature extracted by gray-level co-occurrence matrix and grayscale gradient matrix had similarities and differences in the same and different Chinese herbal medicine. It was concluded that the method can show the texture feature scientifically and quantitatively. It also laid a foundation for the establishment of an automatic identification model, but the parameters still had instability. All these remind us to find some parameters which can show the details of texture feature preferably, thus perfect the extracted method of texture features in Chinese herbal medicine.