Solubility is an important sensory quality attribute of traditional Chinese medicine(TCM) granules. In this paper, 90 batches of granules(30 batches of TCM formula granules, 30 batches of Chinese patent medicine granules and 30 batches of Japanese Kampo granules) were used as the research objects. The turbidity sensor was used to characterize the turbidity curve of the granule dissolution process. The classification system of granule dissolution behaviors was constructed from three dimensions: dissolution degree, equilibrium time, and dissolution mechanism. According to the equilibrium time, the granule dissolution rates were divided into three categories : faster(<100 s), general(101-300 s) and slow(>301 s). According to the turbidity curve profile, the granule dissolution mechanisms were classified into dissolution-controlled type(α-type), dispersion-controlled type(β-type), and dispersion-controlled type followed by dissolution-controlled type(γ-type). The proportion of TCM formula granules, Chinese patent medicine granules and Japanese Kampo granules with complete dissolution or slight turbidity at the end of dissolution was 46.7%, 96.7%, and 10.0%. The proportion of TCM formula granules, Chinese patent medicine granules, and Japanese Kampo granules with faster dissolution rates(<100 s) was 23.3%, 26.7%, and 40.0%. The average dissolution rate of Japanese Kampo granules was faster than that of TCM formula granules, and it was slightly faster than the average dissolution rate of Chinese patent medicine granules. The dissolution mechanism of Chinese patent medicine granules was mainly α-type, while that of Japanese Kampo granules was mainly β-type, and the three types of dissolution mechanisms of TCM formula granules accounted for a relatively average. The purpose of improving the solubility and dispersion of granules can be achieved by combining the comprehensive application of various functional excipients with the small dosage of Japanese Kampo granules and the wide addition scope of excipients. In the process of transforming TCM compound prescriptions into formulas, there is still much room for innovation in formula excipients and process optimization.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Excipients ; Solubility ; Nonprescription Drugs ; Biological Products

We explored the correlations between the color difference values [ΔL~*(lightness), Δa~*(red-green), Δb~*(yellow-blue)] and the content of four active components(including sesquiterpenoids and polyacetylenes) in the powder of Atractylodes lancea and A. chinensis, aiming to provide reference for the quality evaluation of Atractylodis Rhizoma and establish a qualitative model that can distinguish between A. lancea and A. chinensis based on the chromatic values. The tristimulus values(L~*, a~*, and b~*) of 23 batches of A. lancea and A. chinensis were measured by a color difference meter. The content of atractylenolide Ⅱ, β-eudesmol, atractylodin, and atractylone in the 23 batches of samples were measured by high performance liquid chromatography(HPLC). Principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were performed to establish the qualitative models for distinguishing between A. lancea and A. chinensis. SPSS was employed to analyze the correlations between the tristimulus values and the content of the four index components. The results showed that the established PCA and PLS-DA models can divide the A. lancea and A. chinensis samples into two regions, and the tristimulus values of A. lancea and A. chinensis were positively correlated with the content of β-eudesmol and atractylodin. Therefore, the PCA and PLS-DA models can successfully identify A. lancea and A. chinensis, and the appearance color can be used to quickly predict the internal quality of Atractylodis Rhizoma. This study provides a reference for the quality evaluation of Atractylodis Rhizoma and the modern research on the color of Chinese medicinal materials.
Atractylodes ; Sesquiterpenes, Eudesmane ; Drugs, Chinese Herbal ; Rhizome ; Excipients

In recent years, the use of active substances as excipients or as substitutes for other excipients in the design of modern drug delivery systems has received widespread attention, which has promoted the development of the theory of unification of medicines and excipients in the design of traditional Chinese medicine(TCM) preparations. Adopting the theory of unification of medicines and excipients to design drug delivery systems can reduce the use of excipients and thus the cost of preparations, reduce drug toxicity, increase drug solubility and biocompatibility, enhance synergistic effect, and realize targeted delivery and simultaneous delivery of multiple components. However, the research on the application of this theory in the modern drug delivery system of TCM preparations is still insufficient, with few relevant articles. In addition, the TCM active substances that can be used as the excipients remain to be catalogued. In this paper, we review the types and applications of the drug delivery systems with TCM active substances as excipients and describe their common construction methods and mechanisms, aiming to provide references for the in-depth research on the modern drug delivery systems for TCM preparations.
Medicine, Chinese Traditional ; Excipients ; Drugs, Chinese Herbal ; Nanomedicine ; Pharmaceutical Preparations

Oral solid dosage(OSD) occupies a key position in the market of Chinese patent medicines and new traditional Chinese medicines. Processing route is the foundation for the research and development of traditional Chinese medicine OSDs. On the basis of prescriptions and preparation methods of 1 308 traditional Chinese medicine OSDs recorded in the Chinese Pharmacopoeia, we summarized the patterns of processing routes of both modern dosage forms(tablets, granules, and capsules) and traditional dosage forms(pills and powder) and constructed a manufacturing classification system(MCS) based on the processing routes. Based on the MCS, statistical analyses were conducted respectively on medicinal materials, pharmaceutical excipients, extraction solvents in the pretreatment process, crushed medicinal materials, methods of concentration and purification, and methods of drying and granulation, aiming to uncover the process features. The results showed that each dosage form can be prepared via different routes with different processing methods of decoction pieces and raw materials for dosage preparation. The raw materials for dosage form preparation of traditional Chinese medicine OSDs included total extract, semi-extract, and total crushed powder, which accounted for different proportions. The raw materials for traditional dosage forms are mainly decoction pieces powder. Semi-extracts are the main raw materials for tablets and capsules, which account for 64.8% and 56.3%, respectively. Total extracts are the main raw materials for granules, with a proportion of 77.8%. Compared with tablets and capsules, traditional Chinese medicine granules with dissolubility requirements had a larger proportion of water extraction process, a higher proportion of refining process(34.7%), and a lower proportion of crushed medicinal mate-rials in semi-extract granules. There are four ways to add volatile oil to the modern dosage forms of traditional Chinese medicine. In addition, some new technologies and processes have been used in concentration, filtration, and granulation processes of traditional Chinese medicine OSDs, and the application of pharmaceutical excipients is diversified. The results of this study are expected to provide reference for the processing route design and upgrading of OSDs for new traditional Chinese medicines.
Capsules ; Excipients ; Medicine, Chinese Traditional ; Powders

The present study prepared a new type of Ginkgo biloba ketone ester(GBE50) preparation from polyethylene glycol and croscarmellose sodium with good biocompatibility and a certain viscosity by fused deposition modeling(FDM)-type 3D printing technique. Firstly, a cylindrical 3D printing model with a diameter of 9.00 mm and a height of 4.50 mm was established. Subsequently, the 3D-GBE50 preparations with three paths(concentric, zigzag, and grid), different layer heights, and different filling gaps were designed and prepared after the optimization of the proportions of excipients. The morphology, size, chemical properties, and dissolution activity of the 3D-GBE50 preparations were fully characterized and investigated. The results showed that 3D-GBE50 preparations had smooth appearance, clear texture, standard friability, good thermal stability, and stable chemical properties. Moreover, the printing path, layer height, and filling gap were directly related to the release rate of 3D-GBE50 preparations. The dissolution of 3D-GBE50 tablets with zigzag printing path was the fastest, while the dissolution rates of 3D-GBE50 tablets with concentric circle and grid-shaped printing paths were slower than that of commercially available G. biloba Ketone Ester Tablets. In addition, the dissolution of 3D-GBE50 tablets was faster with higher layer height and wider filling gap. As revealed by the results, th FDM-type 3D printing technique can flexibly regulate the drug release activity via controlling the printing parameters, providing effective ideas and methods for the pre-paration of personalized pharmaceutical preparations.
Carboxymethylcellulose Sodium ; Esters ; Excipients/chemistry* ; Ginkgo biloba ; Ketones ; Polyethylene Glycols/chemistry* ; Printing, Three-Dimensional ; Tablets/chemistry* ; Technology, Pharmaceutical/methods*

This study aims to explore the key factors influencing the processing of braised Rehmanniae Radix, optimize the processing, and determine the correlation between the components in different processed products and chroma values, which is expected to add quantitative indexes for the processing of braised Rehmanniae Radix and better control the processing. The weights of the indexes catalpol, rehmannioside D, verbascoside, isoacteoside, 5-hydroxymethylfurfural, reducing sugar, and appearance were calculated based on analytic hierarchy process(AHP) in combination with coefficient of variation, and the overall desirability(OD) was obtained. Box-Behnken design was used to explore the optimal amount of water added, time for soaking with rice wine, and steaming time in the processing of braised Rehmanniae Radix. Colorimeter was employed to determine the chroma of 17 samples and raw samples, and SPSS, Prism, and other software to investigate the correlation between the components in braised Rehmanniae Radix and the chroma values. The results showed that each factor influenced the processing, and the influence followed the order of steaming time>amount of water added>time for soaking with rice wine. The optimal processing process is as below: A total of 100 g medicinal material was added with 7 times of water, followed by soaking with rice wine for 5 h and steaming in a pot for 6 h. The correlation analysis suggested the extremely significantly positive correlation between L~* and content of catalpol, between a~* and 5-hydroxymethylfurfural content, and between b~* and catalpol content, and the extremely significantly negative correlation between L~* and the content of 5-hydroxymethylfurfural and reducing sugar, and between b~* and the content of 5-hydroxymethylfural and reducing sugar. In this experiment, response surface methodology was used to optimize the processing technology of braised Rehmanniae Radix and the optimized process was rational and feasible. The content of chemical components in braised Rehmanniae Radix was significantly correlated with the chroma. This study provided a new method for the quality evaluation of braised Rehmanniae Radix.
Drugs, Chinese Herbal/chemistry* ; Excipients ; Furaldehyde/analogs & derivatives* ; Iridoid Glucosides ; Plant Extracts ; Rehmannia/chemistry* ; Sugars ; Technology ; Water

Three kinds of excipients were selected to investigate the anti-bitterness effect on the extremely bitter characteristics of Andrographis Herba decoction, and the optimal combined anti-bitterness formula was obtained. The preparation principle of different excipients was clarified by virtual screening and experimental verification to explore the advantages of the three kinds of excipients in the combined anti-bitterness effect. Sensory evaluation showed that mPEG_(2000)-PLLA_(2000), γ-cyclodextrin(γ-CD), and aspartame all had good anti-bitterness effect, which reduced the bitterness intensity of Andrographis Herba decoction by 0.5, 6, and 3 points, respectively. The anti-bitterness effect was superior when 0.15% mPEG_(2000)-PLLA_(2000), 1.60% γ-CD, and 0.04% aspartame were combined, and the taste score of the Andrographis Herba decoction decreased from 8 points(severe bitterness) to 1 point(almost no bitterness). Quantum chemistry calculations showed that mPEG_(2000)-PLLA_(2000) reduced the electrostatic potential of bitter groups, which spontaneously combined with it and formed a physical barrier, hindering the binding of bitter components to receptors. The interaction between γ-CD and bitter components was studied. It was found that the surface area and free energy of γ-CD decreased and the dipole moment increased, indicating that γ-CD included bitter components and self-assembled to form supramolecules. Molecular docking showed that hydroxy at position 14 and carbonyl at position 16 of andrographolide, and hydroxy at position 3 and 4, carbonyl at position 14, and five-membered lactone ring of dehydrated andrographolide were possibly the main bitter groups. The binding free energies of aspartame to bitter receptors TAS2 R10, TAS2 R14, and TAS2 R46 were-3.21,-1.55, and-2.52 kcal·mol~(-1), respectively, indicating that aspartame competed to inhibit the binding of bitter groups to bitter receptors. The results of content determination showed that the free amounts of andrographolide and dehydrated andrographolide in Andrographis Herba decoction were 0.23% and 0.28% respectively, while after adding flavor masking excipients, the dissociation amount of andrographolide and dehydrated andrographolide in the decoction decreased to 0.13% and 0.20%, respectively. The above results show that mPEG_(2000)-PLLA_(2000) involves some bitter components into it through micellar self-assembly to reconcile the entrance bitterness, and γ-CD includes the remaining bitter components in the real solution to control the main bitter taste. Aspartame further competes to inhibit the combination of bitter components and bitter receptors, and improves the taste to be sweet. Multi-excipients combined with anti-bitterness strategy significantly reduces the free concentration of bitter substances in Andrographis Herba decoction, and optimizes the taste of the decoction.
Andrographis ; Taste ; Aspartame ; Excipients ; Molecular Docking Simulation

Under the background of the "14th Five-Year Plan" industry development, the pharmaceutical industry has ushered in a critical period of strategic transformation. Pharmaceutical excipients are a major categoryin drugs in addition tomedicinal substances, and the research and development of industrial technologies and innovative products play a decisive role in the development of high-quality drugs. The special drug for children is the focus ofthe pharmaceutical industry in the new era, and the application of standar-dized excipients is a key step indistinguishingbetween adult drugs and special drugs for children. In the context of the policy background in China, this paper reviewed the status quo of excipient industry, technical bottlenecks, application problems of pediatric excipients, and their development hotspots, interpreted the strategic layout of excipient innovation research and development suitable for pediatric preparations, and put forward prospects for their future development technicalroutes to lay a solid foundation for the industry transformation.
Humans ; Child ; Excipients ; Drug Industry ; China ; Pharmaceutical Preparations

This study explored the correlation between color and chemical components of Chrysanthemi Indici Flos(CIF), aiming at providing a reference for its procurement, evaluation, and breeding. Colorimeter and ultra-performance liquid chromatograph(UPLC) were used to determine the color(lightness-shade chromaticity value L~*, red-green chromaticity value a~*, yellow-blue chromati-city value b~*) and chemical components(cynaroside, linarin, luteolin, apigenin, and chlorogenic acid) of 84 CIF germplasms, respectively. Diversity analysis, correlation analysis, regression analysis, and cluster analysis were performed. The results showed that the color and chemical components of CIF were diversified. Chlorogenic acid was in significantly positive correlation with L~* and b~* and significantly negative correlation with a~*. Cynaroside and grey relational grade γ_i of chemical components were in significantly po-sitive correlation with b~* and L~*, respectively, whereas linarin, luteolin, and apigenin had no significant correlation with L~*, a~*, or b~*. The 84 CIF germplasms were clustered into 4 clades. In addition, germplasms in clade Ⅲ had higher γ_i and total color value(E~*_(ab)) than those in other clades, with the best quality and color, and a germplasm with the highest quality, bright yellow color, and highest content of linarin was screened out in this clade. Thus, CIF with bright yellow color had high content of cymaroside and chlorogenic acid and thereby high quality. In summary, the color can be used to quickly predict the quality of CIF. Our results provided data for the evaluation of CIF quality by color and a reference for its procurement and breeding.
Chrysanthemum/chemistry* ; Luteolin/analysis* ; Chlorogenic Acid/analysis* ; Apigenin/analysis* ; Plant Breeding ; Excipients ; Chromatography, High Pressure Liquid/methods*

With Sangtang Yin granule as model drug,and based on the strategy of " unification of medicines and excipients",the feasibility of preparing high drug loading granules with traditional Chinese medicine( TCM) raw powder as carrier was explored. The powder yield,particle size and particle size distribution,fillibility,flowability,hygroscopicity,reconstituability and other key physical properties relating to preparations of 8 herbs( Dioscoreae Rhizoma,Euryales Semen,Atractylodis Macrocephalae Rhizoma,Coicis semen,Poria,Puerariae Lobatae Radix,Puerariae Thomsonii Radix and Coicis Semen by stir-frying with bran) were studied after being smashed,and the feasibility of taking them as excipients of TCM granules was evaluated by co-spray drying,dry granulation and other preparation techniques. According to the results of the physical properties of raw powders,raw powders of Dioscoreae Rhizoma,Euryales Semen and Puerariae Thomsonii Radix had a high powder yield,uniform particle size distribution,good fillibility,poor hygroscopicity and good reconstitutability,with the feature of assisting granule forming. Compared with the prescription of spray dry powder Sangtang Yin without any excipient,the co-sprayed powder had a high yield,good fillibility and compressibility. The yield of dry granules prepared by co-spraying dry powder was increased by more than 10%,and the particles had a uniform color,good fluidity and dissolubility with the drug-loading rate up to 100%. Based on the physical characteristics of TCM raw powder combined with the analysis of the preparation process,Dioscoreae Rhizoma and Puerariae Thomsonii Radix raw powder were selected as the carriers of granule preparations,and Sangtang Yin granule without any excipient was successfully prepared. The findings provide a feasible idea for the preparation of TCM granules with a high drug loading capacity.
Excipients ; Medicine, Chinese Traditional ; Particle Size ; Powders ; Pueraria ; Rhizome