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The mixing process is a critical link in the formation of oral solid preparations of traditional Chinese medicine. This paper took the extract powder of Guizhi Fuling Capsules and Paeonol powder as research objects. The angle of repose, loose packing density, and particle size of the two powders were measured to calibrate discrete element simulation parameters for the mixing process. The discrete element method was used to calibrate the simulated solid density of Paeonol powder and extract powder of Guizhi Fuling Capsules based on the Hertz-Mindlin with JKR V2 contact model and particle scaling. The Plackett-Burman experimental design was used to screen out the critical contact parameters that had a significant effect on the simulation of the angle of repose. The regression model between the critical contact parameters and the simulated angle of repose was established by the Box-Behnken experimental design, and the critical contact parameters of each powder were optimized based on the regression model. The best combination of critical contact parameters of the extract powder of Guizhi Fuling Capsules was found to be 0.51 for particle-particle static friction coefficient, 0.31 for particle-particle rolling friction coefficient, and 0.64 for particle-stainless steel static friction coefficient. For Paeonol powder, the best combination of critical contact parameters was 0.4 for particle-particle static friction coefficient and 0.19 for particle-particle rolling friction coefficient. The best combination of contact parameters between Paeonol powder and extract powder of Guizhi Fuling Capsules was 0.27 for collision recovery coefficient, 0.49 for static friction coefficient, and 0.38 for rolling friction coefficient. The verification results show that the relative error between the simulated value and the measured value of the angle of repose of the two single powders is less than 1%, while the relative error between the simulated value and the measured value of the angle of repose of the mixed powder with a mass ratio of 1∶1 is less than 4%. These research results provide reliable physical property simulation data for the mixed simulation experiment of extract powder of Guizhi Fuling Capsules and Paeonol powder.
Subject(s)
Wolfiporia , Calibration , Powders , Medicine, Chinese Traditional , CapsulesABSTRACT
Objective: The discrete element method (DEM) was used to simulate the angle of repose of Chinese medicine extract powders. The contact parameters between particles and between particles and geometry were calibrated. Methods: The licorice extract powder, the extract powders of Angelicae Pubescentis Radix (Duhuo), microcrystalline cellulose (MCC) and ethyl cellulose (EC) were taken as the research objects. DEM was performed based on the Hertz-Mindlin with JKR Cohesion contact model and particle scaling. The Plackett-Burman design was used to screen out the critical contact parameters that had significant impact on the simulation measurement of the angle of repose. Then, the steepest climbing design was used to determine the best area of critical contact parameters. After that, a regression model between the contact parameters and the simulated angle of repose was established according to the Box-Behnken test results, and the best contact parameter values were optimized and verified. Results: The critical contact parameters selected were particle-particle rolling friction coefficient, particle-particle restitution coefficient and particle-stainless steel restitution coefficient. The calibration range of the built regression model was from 33.30° to 43.64°. The absolute values of the relative error between the simulated values and the experimental values of the angle of repose for four powders were all less than 2.0%, indicating that the established calibration method was accurate and reliable. Conclusion: This article proved the feasibility of calibrating the DEM micromechanical parameters of the Chinese medicine particle system through the macroscopic physical parameter, and laid the foundation for accurate simulation of Chinese medicine pharmaceutical processes like powder mixing and conveying.
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Objective: To optimize the preparation process of Angelicae Sinensis Radix cellwall broken powder (ASR CBP) and evaluate the physical quality of powder. Methods: A HPLC method was established for the determination of five active constituents (ferulic acid, senkyunolide I, coniferyl ferulate, ligustilide and n-butylidenephthalide) of ASR. The Box-Behnken response surface design method was used. The pulverization time, pulverization temperature and sampling capacity in the pulverization process were investigated. The particle size distribution (D90) of the broken wall powder of ASR and the five active ingredients content were used as the response value to construct the response surface model. Under the premise of D90 < 45 μm, the maximum value of the five active ingredients was calculated to optimize the superfine grinding process parameters. A total of 13 physical indicators of D90, coefficient of nonuniformity, particle size distribution width, bulk density, tap density, interparticle porosity, Karl index, specific surface area, pore volume, Hausner ratio, angle of repose, loss on drying and hygroscopicity were used to establish the physical fingerprint of ASR CBP. The similarity evaluation method was used to evaluate the similarity of different batches of ASR CBP. Results: The methodological results of the HPLC method for the determination of the five active ingredients were in accordance with the guidelines. Results of response surface method showed the optimized preparing parameters of ASR CBP technology as follows: 35 min of pulverization time, -10 ℃ of pulverization temperature, and 580 g of sampling capacity. The RSD values between the content and the response surface fitting results of five active ingredients of three batches of cellwall broken powder prepared by the optimal process were all less than 3%. The similarity of the three batches of the optimal process of ASR CBP was above 99.4%. Conclusion: Box-Behnken optimized preparation method of ASR CBP has obvious advantages in retaining the content of active ingredients, especially volatile components. Physical fingerprinting has good practical effects as a tool to evaluate the consistency of physical properties of Chinese material medica powder. The combination of applications helps to achieve a higher quality control level of Chinese medicine cellwall broken powder production.
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Objective: To study the prescription and preparation technology of Huanghuai Tablets and evaluate the physical quality of intermediate particles based on quality by design. Methods: Using Huanghuai (Scutellaria baicalensis and Sophora japonica) extract as the main component, the single factor experiments were used to screen adjuvant, and the forming rate, quality difference, hardness, friability, and disintegration time of tablets were used as indicators to optimize the optimal preparation processing of Huanghuai Tablets by wet granulation process. Physical indicators of granules were characterized by using micromeritics evaluation method. The physical fingerprint of granules were constructed by nine indexes including relative homogeneity index, interparticle porosity, Carr index, bulk density, tapped density, loss on drying, hygroscopicity, Hausner ratio, and angle of repose. The granules physical fingerprint is of great importance to evaluate the quality consistency of different batches of Huanghuai granules and analyze the compressibility of the granules. Results: The optimum formula was Huanghuai granule 0.25 g, 7% croscarmellose sodium, and 2% talc powder. The optimum conditions were as follows: granulated with 16 mesh sieve, dried at 60 ℃ for 1 h, and unified with 18 mesh screen. The similarity of the physical fingerprint of five batches of Huanghuai granules was higher than 0.983, the parameters of five batches of particle parameters were all greater than 0.4, and the parameter profile index was 4.82-5.70, and the good pressure index was from 4.44 to 5.25. Conclusion: The prescription and preparation technology of Huanghuai Tablets and the physical quality of intermediate particles were scientific and reasonable, which can provide ideas and methods for the research and development of Chinese materia medica formula.
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Objective The morphological and particle size distribution of Fritillaria unibracteata under different preparation conditions and the physicochemical property before and after grinding were studied, which provides the experimental basis for the particle size control and application of ultra-fine powder. Methods The single-factor experiment was carried out. The ultra-fine powder was prepared using ball milling method under different milling time, the weight ratio of ball to material, and rotating speed conditions. The powder morphology was observed by scanning electron microscopy. The particle size and particle size distribution of the powder was determined by laser particle size analyzer. The particle size, particle size distribution, expansion degree, total alkaloid content, and other properties of F. unibracteata powder before and after milling were compared. Results The optimum conditions for powder preparation were as follows: The grinding time was 0.5 h, the weight ratio of ball to material was 12:1, the rotating speed was 250 r/min. The volume average particle size of ultrafine powder was (26.92 ± 0.12) μm, and D90 was (45.15 ± 0.18) μm. After grinding, the particle size decreased, the particle size distribution became narrower, the expansion degree and angle of repose increased, the hygroscopicity of powder did not change significantly, the bulk density decreased, and the alcohol-soluble extract content and total alkaloid content increased greatly. Conclusion Moderate grinding can significantly reduce the size of F. unibracteata powder, improve the particle size distribution, increase the total alkaloid content, and help to improve bioavailability.
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Objective To study the influence of different drying technology on the micromeritic properties of Salvia miltiorrhiza extract powder. Methods Taking S. miltiorrhiza extract as model drug, three kinds of extract powders were obtained by vacuum drying, vacuum microwave drying, and spray drying. The properties of powder were evaluated comprehensively with 13 physical indicators, including particle size, span, width, bulk density, tap density, Hausner ratio, angle of repose, compressibility, viscosity, specific surface area, pore volume, moisture content and hygroscopicity. Furthermore, the physical properties of the powder were summarized as homogeneity, stackability, fluidity, compressibility and stability of five aspects, then established the corresponding physical fingerprint spectrum. The powder properties were evaluated by the physical property values. The similarity of the three powders was compared by similarity evaluation method. And the indexes of parameter, parametric profile, and good compression were constructed to analyze the compressibility of the powder. Results The powders obtained by the three kinds of drying methods have poor fluidity and stability. The vacuum drying and vacuum microwave drying powders have good stackability, and the spray-dried powders have excellent homogeneity and compressibility. From the similarity, it can be seen that the similarity of powdery property of spray drying and vacuum drying extract is 79%, and 81.3% with vacuum microwave drying. Conclusion The physical fingerprint of TCM can be used to evaluate the influence of different drying methods on the powder science properties of Chinese medicine extract powder and the influence of physical properties on the formability of the preparation, which provides a new evaluation method for the Chinese medicine extract powder.
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Objective To prepare 15 batches of Chuanxiong Rhizoma standard decoction, and establish HPLC fingerprint and physical fingerprint for quality evaluation. Methods Fifteen batches of Chuanxiong Rhizoma standard decoction were prepared according to preparation conditions of the traditional Chinese medicine (TCM) standard decoction in “Technical Requirements for Quality Control and Standard Formulation of Prescription Granules of TCM (draft for soliciting opinions)”. The mobile phase of HPLC consisted of 0.6% aqueous solution of phosphoric acid and acetonitrile with gradient elution, column temperature of that was 30 ℃, flow rate of that was 1.0 mL/min and detection wavelength of that was 324 nm. Physical fingerprint that consisted of nine secondary indexes (relative homogeneity index, intergranular porosity, Karl index, loose density, vibrating density, dry weight loss, hygroscopicity, Hausner ratio, and angle of repose) was established. Results There were 13 common peaks in the HPLC control fingerprint, and three of them were identified as chlorogenic acid, caffeic acid, and ferulic acid respectively. Taking ferulic acid as a reference peak, the relative retention time and relative peak area of each co-owned peak were analyzed, and the limits of relative retention time and relative peak area of each co-owned peak were specified. The HPLC and physical fingerprint were established, and the similarity should greater than 0.9. Conclusion The HPLC and physical fingerprint of the Chuanxiong Rhizoma standard decoction can be used as reasonable and stable index to evaluate the quality of Chuanxiong Rhizoma standard decoction. Which provides a reference for the preparation and quality control of Chuanxiong Rhizoma dispensing granule.
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OBJECTIVE:To optimize the dry granulation technology conditions for Yinqiao baidu tablet. METHODS:Using granulating difficulty degree and disintegration time as investigation indexes,ratio and amount of accessories microcrystalline cellu-lose and compressible starch in Yinqiao baidu tablet,moisture content of the sprayed powder were screened. Using yield of particle and angle of repose as indexes,L9(34)orthogonal test was used to optimize the wheel pressure,rotating speed and feeding speed in dry granulation technology,and verification test was conducted. RESULTS:The ratio of microcrystalline cellulose and compress-ible starch was 7:3,and mixing ratio of the two with spray powder+inclusion compound was 1:5. The moisture content of spray powder was controlled in 1％-2％. The optimal technology was as follow as wheel pressure of 3.5 MPa,roller speed of 4 r/min and feeding speed of 10 r/min. In verification test,average yield of particle was 69.2％ and angle of repose was 31.5 °. Transfer rate of chlorogenic acid had reached over 92％,and RSD of each index was below 2.53％(n=3). CONCLUSIONS:Each index of parti-cle prepared by optimized accessories formulation and technology shows good reproducibility and feasibility,and the technology is stable and suitable for production.
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Objective: Comparing the differences about physicochemical properties and in vitro dissolution behavior of active ingredients between ultrafine powder and common powder of Eucommia ulmoides to provide the experimental evidence for the ultrafine powder application and the control of particle size. Methods: Ultrafine powders were produced by using ultra mill. Particle size, cell wall breaking rate, morphology, and dissolution were used to evaluate the effect of particle size on microcharacteristic and dissolution behavior of powders of E. ulmoides. Results: There were significant differences between ultrafine and common powders of microcharacteristic. The extraction rates and dissolution rates of the active ingredients of ultrafine powders were higher than those of common powders. Conclusion: An appropriate degree of superfine grinding can increase the wall-breaking rate and promote the dissolution of active ingredients of E. ulmoides, and the dissolution medium has an obvious influence on the dissolution rates. The application of ultrafine grinding technology to E. ulmoides is feasible.
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Objective: To evaluate the effect of the excipients on hygroscopicity of Gushuling Granules and optimize the damp-proof excipients. Methods: Moisture absorption rate was used to optimize the type and ratio of materials; The concentration of ethanol, moisture absorption rate, formability, angle of repose, and appearance of Gushuling Granules were used to optimize the molding technology. Results: The best damp-proofing excipients were as follows: the hybrid materials were lactose-mannitol 4:1, medicine-auxiliary ratio of 1:2, and with 85% ethanol to granulate. Gushuling Granules were good uniform, damp-proofing, and formability, the critical relative humidity was 76%. Conclusion: The preparation technology is stable. The study provides the experimental evidences for the research and development of Gushuling Granules.
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OBJECTIVE:To investigate the effects of amylum pregelatinisatum on the dissolution of calcium dobesilate capsule.METHODS:The amount of amylum pregelatinisatum was optimized by means of the determination of angle of repose and the in vitro dissolution,using the single factor design.The comparisons of effects of different manufactory of amylum pregelatinisatum on formulation and dissolution of capsule were done.RESULTS:Amylum pregelatinisatum could improve significantly the fluidity of powder of capsule.The dissolution of calcium dobesilate capsule were decreased with the increment of amylum pregelatinisatum.It demonstrated that the fluidity of powder and dissolution of calcium dobesilate capsule were the best when the ratio of amylum pregelatinisatum and microcrystalline cellulose was 1∶3 and the amount of sodium carboxymethyl starch was 4 %.The different resource of amylum pregelatinisatum had great effect on the dissoution of the formulation.CONCLUSION:Amylum pregelatinisatum is a favourable filler adjuvant of capsule,but its quantity and the quality should make an optimization.