Process optimization of physicochemical properties of spray-dried Hydrocotyle umbellata L. extract

Abstract Hydrocotyle umbellata L., Araliaceae, is a species that is recommended in Ayurvedic medicine for its effects on the central nervous system, such as anxiolytic and memory-stimulant effects. Despite the medicinal potential of this species, its phytopharmaceutical and technological potential to produce standardized extracts has not been investigated. This study analyzes the influence of spray drying parameters on the contents of the chemical markers (total phenolic, total flavonoid, and hibalactone) and the functional properties of H. umbellata extract. The optimization of drying conditions was performed using a central composite design combined with response surface methodology and desirability function approach. The mathematical models fitted to experimental data indicated that all the evaluated drying parameters significantly influenced the chemical contents. The optimal conditions were: inlet temperature of 120 °C, feed flow rate of 4 mL min-1, and colloidal silicon dioxide:maltodextrin ratio of 16%:4%. Under these conditions, the powder samples had spherical particles and desirable physicochemical and functional properties, such as low water activity and moisture content, good product recovery, reconstitution, and flowability. Thus, spray drying might be a promising technique for processing standardized H. umbellata extracts.

Establishment of Feedforward Control Model for Dry Granulation of Polysaccharide Components Based on Quality by Design / 中国实验方剂学杂志

ObjectiveA feedforward control model for dry granulation of polysaccharide components was established to guide the adjustment and optimization of critical process parameters （CPPs） in the design space， so as to reduce the impact of fluctuations in raw materials properties on the quality of medicines. MethodTaking Astragali Radix extract powder as the model drug， the design space of dry granulation CPPs was determined by Box-Behnken design. Astragali Radix mixed powder with different powder properties were prepared by mixture design， the variance inflation factor （VIF） was used to diagnose the multicollinearity of the powder properties， and principal component analysis （PCA） was used to extract the characteristic data of the model. Radial basis function neural network （RBFNN） was used to establish a feedforward control model for reflecting the relationship between the powder properties of polysaccharide components， dry granulation CPPs and one-time molding rate. ResultThe design space for dry granulation CPPs of polysaccharide components was 16-35 Hz for feeding speed， 10-23 Hz for roller speed， and 10-46 kg·cm-2 for roller pressure. The established RBFNN feedforward control model had a good predictive effect on the one-time molding rate of dry granulation of polysaccharide components， which could be used to guide the adjustment and optimization of CPPs in the design space， the relative error was 0.38%-6.73%， and the average relative error was 3.42%. ConclusionThe established feedforward control model can well reflect the relationship between the powder properties of the polysaccharide components， the dry granulation CPPs and the one-time molding rate of the granules， which can be used to guide the adjustment and optimization of CPPs in the design space， reduce the impact of material property fluctuation on product quality， and provide ideas for promoting the quality of traditional Chinese medicine from passive control to active control.

Powder modificationfor improving content uniformity of Ziyin Yiwei Capsules / 中国中药杂志

Based on the defects in powder properties of the contents of Ziyin Yiwei Capsules, this study screened out the main medicinal slice powders causing the poor powdery properties, and introduced the powder modification process to improve the powdery properties of these slice powders, the pharmaceutical properties of the capsule contents, and the content uniformity of Ziyin Yiwei Capsules, so as to provide a demonstration for the application of powder modification technology to the preparation of Chinese medicinal solid preparations. Through the investigation on the powder properties of the contents of Ziyin Yiwei Capsules, it was clarified that the pulverized particle size of the capsule contents had a good correlation with the pulverization time. According to the measurement results of the powder fluidity and wettability, the quality defects of the capsule contents were caused by the fine powders of Taraxaci Herba and Lungwortlike Herba. "Core-shell" composite particles were prepared from medicinal excipients magnesium stearate and fine powders of Taraxaci Herba and Lungwortlike Herba slices after ultra-fine pulverization to improve the powder properties of the problematic fine powders. Powder characterization data including fluidity and wettability were measured, followed by scanning electron microscopy(SEM) and infrared ray(IR) detection. It was determined that the optimal dosage of magnesium stearate was 2%, and the compositing time was 3 min. The composite particles were then used as content components of the Ziyin Yiwei Capsules. The powder characteristics between the original capsule and the modified composite capsule including the particle size, fluidity, wettability, uniformity of bulk density, and uniformity of chromatism as well as the content uniformity and in vitro dissolution were compared. The results showed that the powder characteristics and content uniformity of the prepared composite capsule were significantly improved, while the material basis of the preparation was not changed before and after modification. The preparation process was proved to be stable and feasible. The powder modification technology solved the pharmaceutical defects that were easy to appear in the preparation of traditional capsules, which has provided experimental evidence for the use of powder modification technology for improving the quality of Chinese medicinal solid preparations and promoting the secondary development and upgrading of traditional Chinese medicinal dosage forms such as capsules.

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.

Prediction of Disintegration Time of Traditional Chinese Medicine Tablets Based on Generalized Regression Neural Network / 中国实验方剂学杂志

Objective:This paper constructs a generalized regression neural network （GRNN） model to predict the disintegration time of traditional Chinese medicine （TCM） tablets. Method:Taking Astragali Radix as a model drug， the mixed Astragali Radix powders with different powder properties were prepared by mixing Astragali Radix extract powders with microcrystalline cellulose and lactose， which were made to Astragali Radix tablets by direct compression method. The powder properties of mixed Astragali Radix powders and the disintegration time of Astragali Radix tablets were determined， respectively. The correlation between the original data was eliminated by principal component analysis （PCA）. The principal component factors were used as the input layer of the GRNN model， and the disintegration time was used as the output layer for network training. Finally， the verification group data was used to predict the disintegration time， and the network prediction accuracy was calculated by comparing with the actual value. Result:Three principal component factors were obtained through PCA by analyzing the original nine variables that were correlated with each other （Hausner ratio， true density， tap density， compression degree， angle of repose， bulk density， porosity， water content and total dissolved solids）， which reduced the complexity of the network. The prediction value of the disintegration time based on this prediction method was in good agreement with the actual value， the error of disintegration time was 0.01-1.34 min and the average relative error was 3.16%. Conclusion:Based on the GRNN mathematical model， the physical properties of Astragali Radix extract powders can be used to accurately predict the disintegration time of Astragali Radix tablets， which provides a reference for studying the disintegration time of TCM tablets.

Design and evaluation of Tiandi Zhenchan Instant Powder based on new concept of “taking drugs without water” / 中草药

Objective: To design and evaluate Tiandi Zhenchan Instant Powder (TZIP) by promoting the new concept of “taking drugs without water”. Methods: The self-designed formula was used to prepare TZIP. Compared with self-made fine powder, TZIP was evaluated by using taste evaluation, powder properties and solubility evaluation as indicators. Results: The powder had the properties of good taste, short oral retention time and good powder properties. Conclusion: Instant powder is an excellent new dosage form. In this paper, TZIP is taken as an example to provide a new dosage form and evaluation reference for promoting the new concept of “taking drugs without water”.

Effects of Superfine Grinding Technology on Powder Properties and Dissolution of Oyster Shell / 中国药房

OBJECTIVE： To study the effects of superfine grinding on the powder properties and dissolution of oyster shell， and to provide experimental basis for its comprehensive exploitation. METHODS： Oyster shells were firstly prepared into ordinary powder by grinder. Then the ordinary powder was prepared into micro-powder Ⅰ （crushing 5 min） and Ⅱ （crushing 10 min） by ultrafine pulverizer. The differences of micromeritic properties were investigated before and after superfine grinding from the aspects of particle size distribution， specific surface area and porosity， angle of repose， bulk density， hygroscopicity， etc. Scanning electron microscope （SEM）， Fourier transform infrared spectroscopy （FTIR） and X-ray powder diffraction （XRD） techniques were used to analyze the morphological characteristics and chemical structure of oyster shell before and after superfine grinding. The dissolution were investigated. RESULTS： Compared with ordinary powder， micropowder Ⅰ and micropowder Ⅱ’s were small in particle size and uniformly distributed， but the particles were easy to adhere and aggregate； the specific surface area， porosity and the angle of repose increased， while bulk density decreased； the hygroscopicity increased. FTIR and XRD showed no significant change in chemical structure of oyster shell after superfine grinding. The dissolution rate of micropowder Ⅱ and micropowder Ⅰ was 18.5％ and 10.3％ at 10 min， and the dissolution of ordinary powder was only 6.4％ at 60 min. CONCLUSIONS： Compared with ordinary powder， oyster shell show obvious differences in powder properties after superfine grinding； the dissolution rate of the powders increases， and there is no significant change in chemical structure.

Effects of three aqueous extraction preprocessing methods on total coumarins extract of Angelicae dahuricae Radix / 中成药

AIM To investigate the effects of aqueous extraction at normal temperature,40 ℃,and water boiling on total coumarins extract of Angelicae dahuricae Radix.METHODS For the extracts Ⅰ-Ⅳ obtained by ethanol reflux extraction and three aqueous extraction preprocessing methods,respectively,UV and HPLC were adopted in the content determination of total coumarins and imperatorin,then the powder properties and dissolution rates were compared.RESULTS The contents of total coumarins in four extracts were 3.98％,6.03％,6.81％ and 4.46％,while those of imperatorin were 0.633％,0.540％,0.465％ and 0.155％,respectively.The angles of repose were 48.455°,42.587°,42.689° and 42.024° with the bulk densities of 0.214,0.324,0.316 and 0.354 g/cm3,respectively.Within 100 min,extract Ⅰ demonstrated higher moisture adsorption rate and equilibrium moisture absorption content than the other three extracts.The accumulative dissolution rates of various extracts were much higher than that of medicinal material fine powder within 120 min.CONCLUSION All the three aqueous extraction preprocessing methods can obviously improve the powder properties of total coumarins extract of A.dahuricae Radix and increase the dissolution rate of medicinal material fine powder.

Analysis on relativity of drying process of extract and pelleting quality of Chinese materia medica formula granule based on powder properties / 中草药

Chinese materia medica (CMM) formula granule is made from CMM extract powder and suitable pharmaceutical excipients, powder properties of CMM extract powder such as the particle size, hydroscopicity, and fluidity directly affect thepelleting quality of CMM formula granule. Drying is one of the indispensable operating units for preparations of CMM extract, which has great influence on the powder properties of CMM extract powder. Therefore, there is a certain correlation between the drying process and pelleting quality of CMM formula granule. Through the literature research, this paper summarizes the engineering principle and characteristics of each main granulation method, analysis of the evaluation factors of pellet quality, and combines with experimental research to explore the correlation between the drying process of CMM extract and pelleting quality of CMM formula granule in the perspective of powder properties. Finally, we puts forward that more attention should be payed to study the drying process of CMM extract, in order to further improve the quality of pelleting quality of CMM formula granule.

Research on Turmeric Fine Pulverizing Process and Its Powder Properties / 世界科学技术-中医药现代化

This paper was aimed to analyze and study the process of Turmeric fine pulverizing; and the powder properties of Turmeric ultra-micro powder after the process. Based on d50, the powder properties of Turmeric ultra-micro powder were summarized by using orthogonal design to select the optimal Turmeric fine pulverizing. Compari-sons were made on powder properties, such as exterior characters, IR spectra, fluidity and hygroscopicity before and after fine pulverizing. The results showed that optimal fine pulverizing process was determined based on orthogonal design. The conditions were that the material was 1 200 g, with water of 5.5% and crushing for 40 min. Compari-son of powder properties of Turmeric powders before and after fine pulverizing showed that as the diameter of the particle decreased. Turmeric particle gradually showed signs of aggregation. At the same time, granular sensation disappeared;the color turned lighter;powder became finer;fluidity was reduced;balanced hygroscopic capacity el-evated. Although the chemical composition and molecular structure had not changed;initial velocity and capacity of hygroscopicity increased, acceleration declined. It was concluded that Turmeric fine pulverizing was a convenient, reliable and practical process, with small size of particle. It can be used for Turmeric fine pulverizing. The compre-hensive evaluation showed that ultrafine powder four as the optimum powder.