Common Problems of Traditional Chinese Medicine Effervescent Tablets and Prospect Analysis of Powder Modification Technology / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） effervescent tablets have the characteristics of rapid disintegration， good taste， and convenient taking， but there are some technical difficulties in the preparation and storage process， which are mainly reflected in the sticking， easy moisture absorption， poor compressibility， and poor stability. The basic physical properties of TCM powder （extract powder， raw powder） are the main cause of these technical problems， and also the key to control the quality of TCM effervescent tablets. Powder modification technology has shown good effects in solving the above problems. The author intended to review the research in the above aspects in recent years， and proposed the following strategies for applying powder modification technology to solve the problems in the production process of TCM effervescent tablets from the three aspects of raw materials， excipients and preparation intermediates：①The application of co-processing technology to the treatment of raw materials and auxiliary materials can solve the problems of sticking， poor compressibility， delayed disintegration， and poor stability. ②Using surface coating technology to treat raw materials and preparation intermediates can improve poor fluidity， poor compressibility and delayed disintegration. ③The hygroscopicity of the preparation can be reduced by using microencapsulation technology to treat the raw material. ④The inclusion technology can improve the clarity and stability of the preparation.

Characterizing flowability of microcrystalline cellulose and its visualizing the correlation of the performance parameters / 药学学报

In this study, multivariate statistical analysis was applied to characterize the flowability of different types of microcrystalline cellulose (MCC), and the visualization of R language was used to explore the intrinsic correlation on its performances. To verify the operability of multivariate statistical analysis, we compared the results of the conventional methods such as repose angle method, Hausner ratio method, Carr's index method and the parameter a of Kawakita equation to determine whether there are significant differences between the conventional ones and multivariate statistical analysis. Moreover, the fillibility and compressibility were characterized by parameters 1/b of Kawakita equation and the means of pressure-tensile strength and compressibility curve method, respectively. The data was analyzed through R language for visualizing the correlation among the performance parameters of MCC. The flowability of the series of microcrystalline cellulose PH (MCCPH) were superior to the series of microcrystalline cellulose WJ (MCCWJ), the compressibility of MCCPH-302 was optimum, and the flowability and fallibility of MCCPH-102 were better than others. The results of conventional methods were consistent with multivariate statistical analysis. The fillibility was positively correlated with flowability, both negatively correlated with compressibility by analyzing correlation coefficient diagram, which was statistically significant (P<0.01). It is reasonable that adopting multivariate statistical analysis to character the flowability of powders, which is more objective than the traditional approach. The correlation visualization of performance parameters of powders provides convenience for screening preparation material via the visualization of R language.

Physical properties and biological effects of mineral trioxide aggregate mixed with methylcellulose and calcium chloride

Abstract Objectives: Methylcellulose (MC) is a chemical compound derived from cellulose. MTA mixed with MC reduces setting time and increases plasticity. This study assessed the influence of MC as an anti-washout ingredient and CaCl2 as a setting time accelerator on the physical and biological properties of MTA. Material and Methods: Test materials were divided into 3 groups; Group 1(control): distilled water; Group 2: 1% MC/CaCl2; Group 3: 2% MC/CaCl2. Compressive strength, pH, flowability and cell viability were tested. The gene expression of bone sialoprotein (BSP) was detected by RT-PCR and real­ time PCR. The expression of alkaline phosphatase (ALP) and mineralization behavior were evaluated using an ALP staining and an alizarin red staining. Results: Compressive strength, pH, and cell viability of MTA mixed with MC/CaCl2 were not significantly different compared to the control group. The flowability of MTA with MC/CaCI2 has decreased significantly when compared to the control (p<.05). The mRNA level of BSP has increased significantly in MTA with MC/CaCl2 compared to the control (p<.05). This study revealed higher expression of ALP and mineralization in cells exposed to MTA mixed with water and MTA mixed with MC/CaCl2 compared to the control (p<.05). Conclusions: MC decreased the flowability of MTA and did not interrupt the physical and biological effect of MTA. It suggests that these cements may be useful as a root-end filling material.

Assessment of radio frequency heating on composition, microstructure, flowability and rehydration characteristics of milk powder

Abstract Radio frequency heating (RFH) provides higher efficiency and more uniform heating zone compared with conventional method. The aim of present work is to evaluate the effect of RFH (at 90 °C for 5 or 10 min) on the changes in composition (protein oxidation and fat distribution), microstructure, flow characteristic and rehydration property of infant milk powder. The results indicate that the concentration of protein dityrosine was slightly enhanced, more free fat appeared on powder surfaces (> 50% increase), and porosity in powder matrix as tested by SEM was increased after RFH treatment. For powder flowability, raw sample had low cohesiveness (specific energy = 4.39 mJ/g), and RFH provided better flowability and decreased compressibility. Moreover, RFH had some negative impacts on wettability and solubility of powder particles with contact angle increase at least 5% and solubility decrease of 2%~4%, indicating worse rehydration abilities. Guggenheim-Anderson-de Boer (GAB) model was applied to fit moisture vapor sorption isotherms, and longer RFH duration leading to higher c values (about 63% increase at 10 min). In addition, the RFH initiated browning reaction as CIE a* values increased from -1.8 to -1.3.

Functionality of Benecel K4M/Carbopol 971P NF matrices in direct compression tablets for controlled release.

The aim of this work is the assessment of the eventual enhancing effects of Carbopol 971P NF on the performance of Benecel K4M as a controlled release agent and its impact on other technological properties such as compactibility and powder flowability. The effect of Carbopol 971P NF and Benecel K4M in the performance of metronidazole tablets with controlled release was assessed using dissolution and compactibility profiles and the flowability of powders. Benecel K4M produces release profiles with an average exponent n=0.711 while Carbopol 971P NF displays average values of n=1.19. The values for tablets containing equal parts of Carbopol 971P NF and Benecel K4M was an average of n=0.947. Metronidazole tablets containing the Benecel K4M/Carbopol 971P NF blend shows a compactibility 2-3 times higher than tablets containing only Benecel K4M. Metronidazole/Benecel K4M blends flow sufficiently at all studied polymer proportions (≤ 30%) while admixtures of metronidazole/Benecel K4M with Carbopol 971P NF flow sufficiently only at polymer proportions ≤ 17%. Carbopol 971P NF enhances the overall performance of Benecel K4M in the same way as Noveon AA1 does, it reduces better the drug release and improves the compactibility, although decreases the flowability.

Improvement of powder flowability and hygroscopicity of traditional Chinese medicine extract by surface coating modification technology / 中国中药杂志

To study the improvement of powder flowability and hygroscopicity of traditional Chinese medicine extract by surface coating modification technology. The 1% hydrophobic silica nanoparticles were used as surface modifier, and andrographis extract powder was taken as a model drug. Three different techniques were used for coating model drugs, with angle of repose, compressibility, flat angle and cohesion as the comprehensive evaluation indexes for the powder flowability. The powder particle size and the size distribution were measured by Mastersizer 2000. FEI scanning electron microscope was used to observe the surface morphology and structure of the powder. The percentage of Si element on the powder surface was measured by energy dispersive spectrometer. The hygroscopicity of powder was determined by Chinese pharmacopoeia method. All of the three techniques can improve the flowability of powder extract. In particular, hygroscopicity of extract powder can also be improved by dispersion and then high-speed mixing, which can produce a higher percentage of Si element on the powder surface. The improvement principle may be correlated with a modifier adhered to the powder surface.

Solidification of magnolol phospholipid complex with polyvingypyrrolidone / 中国中药杂志

In this study, magnolol phospholipid complex (MPC) was prepared and solidified with polyvingypyrrolidone (PVPP). The influence of PVPP on MPC's flowability, dissolution and oral bioavailability was investigated. The results of phase characterization using differential scanning calorimetry (DSC), infrared spectroscopy (IR), and scanning electron microscopy (SEM) showed that magnolol existed in solidified powder and MPC in an amorphous state. In flowability and dissolution experiments, solidified powder showed significant superiority. At the same time, it showed a higher oral bioavailability compared with MPC, with AUC0-∞ of 73.47 μg•h•mL⁻¹ vs. 63.48 μg•h•mL⁻¹. This process for solidifying powder with PVPP is simple and convenient.

Influence of different types of lactose on powder flow and tablets dissolution.

The objective of this study was the evaluation of different types of lactose on the powders flow properties and dissolution of tablets of formulations with captopril and amoxicillin. Data of powders flow rate, compressibility index and dissolution profiles of tablets are presented. The powders flow rate showed higher sensitivity to small changes in their properties, compared to compressibility index. SuperTabs 21AN and 24AN flow at least 20 times faster than Lactopress and lactose NF. Lubrication increases the flow rate, maintaining the observed comparative differences. Dilution of lactoses with 50% captopril or amoxicillin reduces drastically the powder flow, producing also an equalizing effect. The greater flowability of SuperTabs, compared to other types of lactose, practically disappears. Dissolution of lubricated and unlubricated lactose tablets show a much faster dissolution of SuperTab 21AN tablets followed by Lactopress, lactose NF and SuperTab 24AN tablets. Dilution of lactoses with 50% captopril displays a quite smaller dissolution rate with a comparative similar behavior as observed before while dilution with amoxicillin show an equalizing effect of drug dissolution with minor differences between lactoses. The effect of lactose excipients on dissolution is attributed in a greater extent to mechanical properties of their tablets than to differences in solubility and dissolution.

Noveon AA1 as enhancer of HPMC as a direct compression matrix for controlled release.

This work aimed the assessment of the effect of different proportions of Noveon AA1 on performance of HPMC as a controlled release agent for direct compression tablets. The functionality of polymer blends was determined using dissolution profiles, compactibility profiles and the powders compressibility index. Ten percent HPMC allows a metronidazole release after 3 h of 85%, an exponent n=0.48 and a release constant K=6.9. The increasing polymer substitution by Noveon AA1 decreases drug dissolution up to 36%, increases the exponent to 1.0 and decreases the release constant to 0.2%. The metronidazole/HPMC blend shows a slower increasing and a lower potential of tablets compactibility (20 N) while its increasing substitution by Noveon AA1 attains faster increasing and higher potential compactibilities (39 N). The metronidazole/HPMC (90:10) blend shows a low compressibility index (14%) that increases up to 33.2% with increasing Noveon AA1 proportions. Noveon AA1 proportions ≤ 5% display good/passable powder flowabilities. Noveon AA1 enhances the overall controlled release performance of HPMC, inducing zero order release patterns without lag or burst effects and reducing drug release more efficiently. Noveon AA1 also improves the compactibility of metronidazole/HPMC blends, however, decreases their flowability; flowability is acceptable only at lesser polymer proportions.

Relationship between granule flowability under different humidity and quality of guaifenesin sustained release tablet / 中国药学杂志

OBJECTIVE: To study influence of humidity on granule flowability, explore relationship between flowability and quality of guaifenesin sustained tablet, give a basis for industrialization. METHODS: By hygroscopicity study, CRH was measured. After 10 days in RH 33%, 60%, 75%, 84%, 92.5%, flowability of granule and quality index of tablet, such as appearance, extremum of weighty friability was measured and compared with result of 0 d. Functional relationship between micromeritics parameter and quality index of tablet was fitted. RESULTS: CRH of granule is between RH 67%-68%. When relative humidity is above RH 60%, flow-ability and quality of tablet is changed obviously. Used compressbiliity as X1, repose angle as X2, extremum of tablet weight as Y1, friability as Y2, linear relationship of them is Y1 = 0.192X1+ 0.092X2- 7.398 (r = 0.9921), Y2= 0.069X1 + 0.087X2 - 3.505 (r = 0.9881), when P < 0.001, the equations had statistical significance in the range of observation. CONCLUSION: Relative humidity of production and storage of granule should less than RH 60%. Functional relationship between micromeritics parameter of granule (compressbiliity and repose angle) and quality index of tablet (extremum of weighty friability) had statistical significance in the range of observation. Copyright 2012 by the Chinese Pharmaceutical Association.

Co-processed extracts of Cassia angustifolia Vahl, Fabaceae, and Maytenus ilicifolia (Schrad.) Planch., Celastraceae, for production of high load tablets

The aim of this study was to investigate the feasibility of a co-processing technique for improving the manufacturing properties of Maytenus ilicifolia (Schrad.) Planch., Celastraceae, and Cassia angustifolia Vahl, Fabaceae, extracts in order to obtain tablets containing a high dose of such extracts. An experimental mixture design was used to optimise the formulation composition. Flowability parameters, such as compressibility index, time flow and angle of repose, were determined. Additional important industrial parameters, such as granulometry, bulk density and moisture stability, were also studied. The results demonstrated that co-processing technique was able to improve the flowability of vegetal extracts, making these materials suitable for a direct compression process. The contour plots revealed that formulations with a higher amount of lactose produced the best flow results as well as a larger particle size and a greater bulk density. Tablets from co-processed extracts containing lactose as majority diluent showed appropriate physical-chemical characteristics and presented a more stable moisture sorption behaviour compared to commercial gelatine capsules.

Study on the change of red blood cell membrane after leukocyte filteration / 重庆医科大学学报

Objective:To explore the change of membrane protein composition of red blood cells after the blood being filtered by leukocyte filter.Methods:A total of 400ml blood from 20 healthy donors were equally divided into control group and filtered group according to the paired design.SDS-PAGE electrophoresis was done for the red blood cell membrane protein of both groups.Bandscan protein analysis software was used to analyze the composition of membrane protein.Fluorescence degree of polarization was detected by fluorescence polarization method and membrane flowability was counted.Plasma concentration of free hemoglobin(FHb) was detected weekly.Results:The band Ⅰ,Ⅱ and Ⅶ parotein of membrane skeleton of the filtered group decreased significantly compared with those of the control group(P﹤0.01),and the fluorescence degree of polarization and microviscosity of the filtered group was higher(P﹤0.01).There was significant difference of plasma FHb between filtered group and control group at each week except week 0,and that of the filted group was higher(P﹤0.01).Conclusion: Leukocyte filter can bring damage to erythrocyte membrane protein composition.Membrane microviscosity and plasma concentration of free hemoglobin increase and membrane flowability decreases.