Research progress of powder modification of TCM based on particle design theory / 药学学报

Particle design, based on the concept of "quality by design", combines the elements of microbiology, formulation science, heat and mass transfer, solid state physics, powder science, and nanotechnology. It is widely used to develop particles with excellent functional properties. Without affecting the active ingredients, the modification technology of traditional Chinese medicine (TCM) powder based on particle design theory, could improve the flowability, tabletability, disintegration and dissolution behavior, hygroscopicity, wettability, and other functional properties at the physical structure level. This greatly promotes the development of solid preparations of TCM. The present review aims to summarize and discuss the research progress of powder modification of TCM from the perspective of the theory of particle design, powder modification technology, equipment used for powder modification, application in TCM and modification mechanism mainly based on researches published in recent ten years. This review could provide ideas and theory basis for the development of particle design.

Research Progress of Transmembrane Transport of Oral Nanoparticles in Gastrointestinal Tract / 中国实验方剂学杂志

Oral nanoparticles （NPs） has gradually become a approach to improve oral bioavailability of biopharmaceutics classification system （BCS） Ⅱ， Ⅲ， Ⅳ drugs， and the transmembrane transport mechanism in the gastrointestinal tract largely depends on physicochemical characteristics of NPs. It would be beneficial to design the NPs with high transport efficiency and effectively improve the oral bioavailability of drugs by adopting a reasonable research model to analyze the transmembrane mechanism of the oral NPs and exactly reveal the relationship between the physicochemical properties and the transport mechanism of NPs. This review focused on summarizing the transmembrane approaches of oral NPs， comparing the advantages and disadvantages of the common cell models， concluding the potential interaction between the physicochemical properties and transmembrane process of NPs， and proposing the research strategy of transport mechanism based on in situ intestinal perfusion， with the purpose of discovering a suitable research model for studying the transport mechanism of different NPs， providing a basis for regulating the transport performance of the NPs to improve the oral bioavailability， and expanding the application of oral NPs in the development of new drugs.

Particle design for improving content uniformity of Hewei Jiangni Capsules / 中国中药杂志

Targeting the poor powder characteristics of the contents in Hewei Jiangni Capsules, this study characterized the powder properties of the contents and employed particle design technique for improving the content quality. The content composite particles of Hewei Jiangni Capsules prepared by the particle design technique were evaluated by scanning electron microscopy(SEM), followed by infrared ray(IR), content uniformity, and in vitro dissolution detection. It was found that there was a good correlation between the crushed particle size of slices and the crushing time, and the calcined Haematitum was responsible for the poor content uniformity. After the fine powder of calcined Haematitum was super-finely ground for 8.5 min and those of the other contents in the capsule for 1 min, they were prepared into the composite particles, whose property characterizations were compared with those of the physical mixtures. The content uniformity of the prepared composite particles was significantly improved, and the preparation process was stable and reliable. The adoption of particle design technology to correct the poor uniformity of the physical mixture, solve the pharmaceutical defects of Hewei Jiangni Capsules, and improve the quality of prescriptions has provided important reference for the clinical application and development of Chinese medicinal preparations.

Particle design for improving taste and homogeneity of traditional Chinese medicinal powder: taking Zhuhuang Chuihou Powder as an example / 中国中药杂志

Due to the complex source and different physical and chemical properties of traditional Chinese medicines(TCM) powder, there are many common pharmaceutical problems in its preparation, such as large particle size difference, poor mixing uniformity, and poor compliance with oral intake, which has directly affected the quality of solid preparations as well as their clinical efficacy and safety. This study observed the property of Zhuhuang Chuihou Powder and extract its pharmaceutical defects. It was found that realgar and calcined Borax in Zhuhuang Chuihou Powder were heavy in texture and toxic, and they were easy to be isolated, indicating the potential safety hazard. At the same time, Coptidis Rhizoma and Phellodendri Chinensis Cortex were the main sources of its bitterness. Therefore, based on the idea of "drug-excipients unity", the particle design technology was used to prepare core/shell-type composite particles with bitter medicines as the core and mineral medicines as shell. Both infrared spectroscopy and scanning electron microscopy results indicated the formation of composite particles, and the taste of these composite particles were improved. Compared with the physical mixtures, the composite particles exhibited significantly decreased RSD values in the content uniformity of berberine hydrochloride, arsenic disulfide, and sodium tetraborate and appearance uniformity. The introduction of particle design technology solved the problem of uneven dispersion of Zhuhuang Chuihou Powder, thus ensuring its uniform dispersion, stability, and control and improving the quality of the original preparation. This has provided a scientific basis for the quality control of TCM powder.

Application of design technology for preparing Lingzhu Powder particles based on solvent evaporation method / 中国中药杂志

Targeting the deficiencies of Lingzhu Powder, this study introduced the particle design technology to improve its quality. Based on the mechanism of particle design for powder and the characteristics of solvent evaporation method, composite particles consisting of Succinum, Cinnabaris, and artificial Bovis Calculus were prepared. And the powder properties of composite particles and physical mixtures as well as the content uniformity of toxic components were investigated for exploring the technological advantages of particle design in improving the quality of Lingzhu Powder. The results showed that the composite particles prepared using solvent evaporation method and particle design technology were micro-particles, and the stable agglomerate structure could be observed under SEM. Composite particles exhibited better fluidity and compliance in oral intake than physical mixtures. The differences in chromatism, bulk density, and content uniformity of the composite particles were smaller than those of physical mixtures, and the corresponding RSD values \[4.8%, 1.8%, 3.4%(bilirubin), and 0.63%(HgS), respectively\] were smaller. The solvent evaporation combined with particle design technology can be utilized to significantly improve the quality of Lingzhu Powder, which has provided new ideas for the optimization of the quality of traditional Chinese medicinal powder.

Study on anti-hygroscopic technology based on correlations between particle spatial properties and hygroscopicity of Chinese medicinal extracts / 中国中药杂志

This study was designed to investigate the correlations of the spatial structure properties of Chinese medicinal extracts with hygroscopicity and the anti-hygroscopic techniques. With Poria extract used as the model drug, pregelatinised starch and microcrystalline cellulose at different ratios were added into Poria fluid extract for preparing powder particles with diverse spatial structures using different drying processes. Then, their hygroscopic behaviours were characterized by equilibrium hygroscopicity(F~∞) and semi-hygroscopic time(t_(1/2)). The correlations of the hygroscopicity of each powder with the spatial structure properties such as particle size(D_(90)), porosity(ε), true density(ρ_t), and surface element distribution were analyzed using partial least-squares method. The F~∞ and t_(1/2) values of Poria extract prepared by three drying methods were sorted in a descending order as follows: F~∞(spray drying>drying at ordinary pressure>drying at reduced pressure); t_(1/2)(drying at reduced pressure>drying at ordinary pressure>spray drying). The powder obtained by spray drying showed a spherical structure with the smallest particle size and intra-particle ε but relatively stronger hygroscopicity. The large-scale surface element enrichment of the powders dried by reduced pressure effectively reduced their hygroscopicity. F~∞ and t_(1/2) were negatively correlated with ε but positively with D_(90), and the interactive influence of each spatial structural properties was not significant. There existed a correlation between the spatial structure of the powder particles of Chinese medicine extracts and their hygroscopicity, and the hygroscopicity could be improved by designing the spatial structure. This study has provided some practical basis for developing the moisture-proof technology of Chinese medicinal preparations.

Study on mixing uniformity of powder based on raw material powder of Qingrun Pill design technology and near infrared spectroscopy / 中草药

Objective: Using Qingrun Pill as model drug, the raw material powder of Qingrun Pill with uniform mixture was prepared. The rapid analysis method was used to evaluate the mixing uniformity of Qingrun Pill raw materials. Methods: Based on the particle design technology, the raw material powder of Qingrun Pill was prepared, the core-shell particles were established with the particle size as the index, and the mixing uniformity of the raw material powder of Qingrun Pill was analyzed with the standard deviation of moving block as the index by near infrared spectroscopy. Finally, it was verified by HPLC. Results: According to the particle design technology, the raw material powder of Qingrun Pill was designed. Shell particles: Rheum officinale and other materials; Nuclear particles: Scutellaria baicalensis and other materials; The particle size (d0.9) of shell particles at ultrafine grinding for 12 min was about 5 μm, and that of nuclear particles at ultrafine grinding for 6 min was about 130 μm. The ratio of nuclear particles to shell particles was more than 10:1, which met the requirements of particle design. Near-infrared spectroscopy showed that shell particles were ultrafine comminuted for 12 min, and then the nuclear particles were mixed evenly for 6 min. Conclusion: In this study, Qingrun Pill powder was prepared based on particle design technology, and the mixing uniformity of powder was evaluated by near infrared spectroscopy. This method is simple and feasible, real-time, and without destroying the sample.

Improving hygroscopicity of fermented Cordyceps powder based on particle design technology of traditional Chinese medicine / 中国中药杂志

Commonly used dosage forms of fermented Cordyceps powder products are capsules and tablets. The hygroscopicity of the powder,as one of the important parameters in the tableting process,has important effects on the tabletting process of the tablets. How to improve the hygroscopicity of powder is of great significance for the development of new composite particles. Therefore,particle design technology was used in this study to prepare composite particle powder,and its hygroscopicity was compared with fermented Cordyceps powder and physically mixed powder. By preparing three different types of powders,the equilibrium moisture absorption,particle size,scanning electron micrograph,angle of repose,contact angle and compression degree were compared to observe the effect of traditional Chinese medicine particle design technology on improving the hygroscopicity of the fermented Cordyceps powder. The results showed that the equilibrium moisture absorption was 21. 2%,19. 6%,14. 5% respectively for the fermented Cordyceps powder,physically mixed powder and composite particle powder; the median diameter was(49. 751± 0. 280),(59. 183± 0. 170),(12. 842±0. 080) μm,respectively; the mode diameter was(185. 479±1. 372),(173. 964± 1. 104),(61. 671± 0. 979) μm,respectively. In the scanning electron micrograph of the composite particle powder,it can be clearly seen that the fermented Cordyceps powder had hydrophobic gas phase nano-silica with a fixed shape and uniform size. The angle of repose was(50. 63 ± 0. 75) °,(49. 25 ± 0. 43) °,(48. 33±0. 84) ° respectively; the contact angle was(7. 4±0. 2) °,(8. 2±0. 3) °,(15. 0±2. 6) ° respectively; and the compression degree was(38. 2±1. 3) %,(35. 8±0. 2) %,(32. 5±2. 6) % respectively. This study showed that after treatment by the vibrating ultrafine pulverizer,the fermented Cordyceps powder particles had obvious and uniform small particle hydrophobic gas phase nano-silica adhered to form a partially wrapped coating structure,which reduced the contact surface of fermented Cordyceps powder with the outside world,thereby reducing the hygroscopicity of the composite particle powder. It further demonstrated that the hygroscopicity of fermented Cordyceps powder can be improved by particle design.

Systematic review and comment on modern study of Xiaojin Pills / 中国中药杂志

Xiaojin Pill, was firstly recorded in Life-saving Manual of Diagnosis and Treatment of External Diseases, with its primitive name of "Xiaojin Dan". Xiaojin Pill is a classic prescription for treating carbuncle and it is the first choice for Chinese medicine in the clinical treatment of hyperplasia of mammary glands. In this paper, the literature reports on Xiaojin Pills were summarized and the historical evolution, material basis, pharmacological action, quality control and other problems were systematically discussed to explore the potential problems in every aspect of the development status, and put forward the development countermeasures, providing reference for the modernization research and development of Xiaojin Pills.

Research progress on modification technology and equipment of Chinese materia medica powder / 中草药

Chinese materia medica (CMM) powder has poor mobility, hygroscopic, viscous and easy reunion because of the complex physical and chemical properties. In recent years, pharmacy workers used domestic and foreign reference materials, chemicals, drugs and other chemical powder modification technology to improve the physicochemical properties of CMM powder, and have made some progress. This article summarizes the common modification technology and equipment of CMM powder, puts forward the basic ideas and the development prospects of CMM powder modification.

Optimization and evaluation of intermediate uniformity in Chinese medicine pill powders based on particle design principle:exemplifying by Xiaojin Pills / 药学学报

Based on the principle of particle design, the powder of Xiaojin Pills was prepared, and the quality uniformity was investigated by means of powder characterizations and content uniformity. By studying the mixed crushing rules of the classified materials and the design principle of the powder particles of Chinese medicine, the powder of the Xiaojin Pills was prepared. At the same time, the manmade mixed powder and the control powder prepared by pharmacopoeia were prepared. The mixed homogeneity of the three powders was evaluated by particle size distribution and color difference. The GC-MS and LC-MS/MS were used to study the homogeneity of their contents. The best preparation process of particle design powder is:materials easily crushed are smashed for 50 min in the vibrating ultrafine mill with -15℃, then add the materials difficultly crushed into the mill and let them crushed together for 3 min. The particle size range of manmade mixed powder was the largest with the particle size difference being more than 100 microns, the RSD value being 26.07%. The particle size range was more than 50 microns in the powder prepared by pharmacopoeia, and the RSD was nearly 15%. The difference in particle size was only around 4 μm and the RSD value was 3.18%. The color difference test showed that the composite chromatism (dE*) value of the powder prepared by pharmacopoeia was the largest for the RSD was 84.56%. The RSD of manmade mixed powder and the powder prepared by Pharmacopeia were 53.83% and 32.83%, respectively. The RSD value of the particle designed powder's muscone content is about 50% of the other two kinds of powders. The contents of 10 components in powders were determined by LC-MS/MS. The RSD values of the particle designed powder were much smaller than other two kinds of powders. Results indicate that the uniformity of the particle designed powder is better than other two kinds of powders. Chinese medicine particle design technology can effectively improve the uniformity of traditional Chinese medicine powder.

Recent Progress of Particle Design Engineering Based on Surface Free Energy / 中国药学杂志

Presently interests are growing in the field of surface free energy(SFE). With the further research, more particle design engineering based on SFE are summarized via characterizing the related properties of SFE during the process of particle design. SFE of materials will vary with changing the physical properties of particles via modifying the surface of particles with particle design. In this study, we summarized the application of SFE in powder micronization, particle modification, mixing, coating, pelletilization and granulation, etc. Dispersive-polar model and adhesion-cohesion model were established based on the parameters of SFE. The application of the two models were also illustrated in the particle design engineering.

Preparation and characterization of Indigo Naturalis-Alumen composite particles based on particle design principle / 中草药

Objective: To prepare and characterize Indigo Naturalis-Alumen (INA) composite particles with core-shell structure based on the particle design principle. Methods: The preparation time of shell particles and composition time of composite particles were studied using particle size and contact angle as evaluation indexes, respectively. Four kinds of powders including Indigo Naturalis fine powder, Alumen fine powder, INA mixture, and INA composite particles were prepared respectively; Their properties such as particle size, powder color, microstructure, distribution of surface elements, and crystal structure were compared, so as to study the core-shell structure of composite particles. Results: During the period of the preparation, the shell particles were added into vibromill and ground for 17 min separately, and then the core particles were added and ground with shell particles together for 5 min. There was no difference between the composite particles and shell particles in surface wettability. The median diameter (d0.9) of the composite particles was 32.818 μm, which was much smaller than that of the mixture. The color and surface elements distribution were highly similar to the shell particles. In SEM, the microstructure that the surface of big particles coated with a large number of small particles could be observed. In X-ray diffractogram, many characteristic absorption b ands of the core particles were disappeared or decreased. Conclusion: INA composite particles with core-shell structure are prepared successfully, the surface properties are similar to the shell particles and are different with the core particles.