Online preconcentration and determination of five alkaloids in Yangxinshi tablet by large-volume sample stacking and micelle to solvent stacking in cyclodextrin-modified electrokinetic chromatography.

The two-step preconcentration technique consisting of large-volume sample stacking (LVSS) and micelle to solvent stacking (MSS) in cyclodextrin-modified electrokinetic chromatography (CDEKC) was developed for the analysis of five cationic alkaloids in complex Chinese herbal prescriptions. Relevant parameters affecting separation and stacking performance were optimized separately. Under the optimal LVSS-MSS-CDEKC conditions, less analysis time and organic solvent were required, and the enhancement factors of analytes ranged from 12 to 15 compared with the normal CDEKC separation mode. Further, all validation results demonstrated good applicability and multiple alkaloids (epiberberine, dehydrocorydaline, jatrorrhizine, coptisine and berberine) in Yangxinshi tablet (YXST) have been simultaneously determined. This approach presents powerful potential for the determination of multiple components in complex preparations of Chinese medicine.

Development of an easy-to-set-up multiple heart-cutting achiral-chiral LC-LC method for the analysis of branched-chain amino acids in commercial tablets.

In this paper, the development and application of a multiple heart-cutting achiral-chiral LC-LC method (mLC-LC) for the analysis of dansylated (Dns) branched-chain amino acids in commercial tablets are described. In the first dimension, a Waters Xbridge RP C18 achiral column was used under gradient conditions with buffered aqueous solution and acetonitrile. The elution order Dns-valine (Dns-Val) < Dns-isoleucine (Dns-Ile) < Dns-leucine (Dns-Leu) turned out with full resolution between adjacent peaks: 7.25 and 1.50 for the Val/Ile and the Ile/Leu pairs, respectively. A "research" validation study was performed, revealing high accuracy (Recovery%) and precision (RSD%) using two external set solutions, respectively, in the range 93.7%-104.1% and 0.4%-3.2%. The C18 column was connected via a two-position six-port switching valve to the quinidine-based Chiralpak quinidine-anion-exchange chiral column. A water/acetonitrile, 30/70 (v/v) with 50 mM ammonium acetate (apparent pH of 5.5) eluent allowed getting the three enantiomers' pairs resolved: RS equal to 4.3 for Dns-Val and Dns-Ile, and 1.7 for Dns-Leu. The application of the mLC-LC method confirmed that the content of Val, Ile, and Leu in the tablets was compliant with that labeled by the producer. Only l-enantiomers were found in the food supplement, as confirmed by LC-MS/MS analysis.

Combination of large-volume sample stacking with polarity switching and micelle electrokinetic chromatography for the analysis of anion compounds in Yangxinshi tablets.

INTRODUCTION: Yangxinshi tablet (YXST) is a traditional Chinese medicine preparation characterized by its high efficacy and safety for the treatment of cardiovascular diseases. Anionic compounds have been revealed as potential active components. However, there is currently limited research regarding its quality control. OBJECTIVE: We aimed to establish a strategy for the simultaneous separation and determination of five key anionic compounds in YXST. METHOD: A sensitive and efficient analytical method was developed and applied for the simultaneous separation and determination of five key compounds in YXST using large-volume sample stacking with polarity switching and micelle electrokinetic chromatography (LVSS-PS-MEKC) coupled with diode array detection. Crucial parameters, including sample volume, applied voltage, composition and pH of the running buffer, concentration of organic modifier, and switching time of the polarity, were systematically evaluated and optimized using a single variable method to enhance separation performance. Furthermore, the impact of cyclodextrin and sodium dodecyl sulfate as electrolyte modifiers was also investigated. RESULTS: Under the optimal conditions, baseline separation of the five compounds (daidzein, puerarin, glycyrrhiztinic acid, chlorogenic acid, and salvianolic acid B) was achieved within 20 min. In comparison to the conventional MEKC mode, the constructed LVSS-PS-MEKC method exhibited a more than sixfold increase in the enrichment factor. The method was validated in terms of linearity, precision, accuracy, 24 h stability, and recovery and successfully applied to analyze YXST samples. CONCLUSION: A sensitive strategy was developed for the simultaneous separation and determination of five key anionic components in YXST, offering a robust and efficient strategy for pharmaceutical analysis.

Chemical Profiling of Shen-Wu-Yi-Shen Tablets Using UPLC-Q-TOF-MS/MS and Its Quality Evaluation Based on UPLC-DAD Combined with Multivariate Statistical Analysis.

Shen-Wu-Yi-Shen tablets (SWYST) is a traditional Chinese medicine prescription used for treating chronic kidney disease (CKD). This study aims to characterize the constituents in SWYST and evaluate the quality based on the quantification of multiple bioactive components. SWYST samples were analyzed with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and a data-processing strategy. As a result, 215 compounds in SWYST were unambiguously identified or tentatively characterized, including 14 potential new compounds. Meanwhile, strategies based on characteristic fragments for rapid identification were summarized, indicating that the qualitative method is accurate and feasible. Notably, the glucose esters of laccaic acid D-type anthraquinone were first found and their fragmentation patterns were described by comparing that of O-glycoside isomers. Besides, based on comparisons of the cleavage ways of mono-acyl glucose with different acyl groups or acylation sites, differences in fragmentation pathways between 1,2-di-O-acyl glucose and 1,6-di-O-acyl glucose were proposed for the first time and verified by reference substances. In addition, a validated UPLC-DAD was established for the determination of 11 major bioactive components related to treatment of CKD (albiflorin, paeoniflorin, 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-d-glucoside (TSG), 1-O-galloyl-2-O-cinnamoyl-ß-d-glucose, emodin-8-O-ß-d-glucoside, chrysophanol-O-ß-d-glucoside, aloe-emodin, rhein, emodin, chrysophanol and physcion). Moreover, TSG and 1-O-galloyl-2-O-cinnamoyl-ß-d-glucose were found as the quality markers related to the origins of SWYST based on multivariate statistical analysis. Conclusively, the findings in this work provide a feasible reference for further studies on quality research and mechanisms of action in treating CKD.

DCTPP1, a reliable Q-biomarker for comprehensive evaluation of the quality of tripterygium glycoside tablets based on chemical references.

BACKGROUND: As first-line clinical drugs, tripterygium glycoside tablets (TGTs) often have inconsistent efficacy and toxic side effects, mainly due to inadequate quality control. Therefore, clinically relevant quality standards for TGTs are urgently required. PURPOSE: Based on chemical substances and considering pharmacological efficacy, we aimed to develop an effective quality evaluation method for TGTs. METHODS: Representative commercial samples of TGTs were collected from different manufacturers, and qualitative UHPLC/LTQ-Orbitrap-MS and quantitative UHPLC-MS/MS analysis methods were successfully applied to evaluate their quality similarities and differences based on their chemical properties. Then the anti-immunity, anti-inflammatory and antitumor activities of TGTs and related monomers were evaluated using Jurkat, RAW264.7, MIA PaCa-2, and PANC-1 as cellular models. Subsequently, we predicted and verified small molecule-DCTPP1 interactions via molecular docking using the established DCTPP1 enzymatic activity assay. Finally, we performed a gray relational analysis to evaluate the chemical characteristics and biological effects of TGTs produced by different manufacturers. RESULTS: We collected 24 batches of TGTs (D01-D24) from 5 manufacturers (Co. A, Co. B, Co. C, Co. D, Co. E) for quality evaluation. The chemical composition analysis revealed significant differences in the substance bases of the samples. The D02, D18-D20 samples from Co. B constituted a separate group that differed from other samples, mainly in their absence of diterpenoids and triterpenoids, including triptolide, triptophenolide, and triptonide. In vitro anti-immunity, antitumor and anti-inflammatory tests using the same TGT concentration revealed that, except for D02, D18-D20, the remaining 20 samples exhibited different degrees of anti-immunity, antitumor and anti-inflammatory activity. Our experiments verified that triptolide, triptophenolide, and triptonide were all DCTPP1 inhibitors, and that TGTs generally exhibited DCTPP1 enzyme inhibitory activity. Moreover, the inhibitory activity of D02, D18-D20 samples from Co. B was much lower than that of the other samples, with a nearly tenfold difference in IC50. Further comprehensive analysis revealed a high correlation between DCTPP1 enzyme inhibition activity and the anti-immunity and antitumor and anti-inflammatory activities of these samples. CONCLUSION: The established DCTPP1 enzymatic activity assay proved suitable for quantitative pharmacological and pharmaceutical analysis to complement the existing quality control system for TGTs and to evaluate their effectiveness.

Holistically assessing the quality consistency of compound liquorice tablets from similarities of both all chemical fingerprints and the integrated dissolution curves by systematically quantified fingerprint method.

In recent years, traditional analytical methods have failed to meet the widespread use of multi-component Chinese pharmaceutical formulations. To solve this problem, this study proposed a comprehensive analytical strategy using compound liquorice tablets (CLTs) as an example, both in terms of chemical quality and dissolution curve consistency. Firstly, the peak purity of the two wavelengths was checked using dual-wavelength absorbance coefficient ratio spectra (DARS) to avoid the fingerprint bias caused by peak purity. Secondly, liquid-phase dual-wavelength tandem fingerprint (DWTF) of 38 batches of CLTs was established for the first time. The two analytical methods were also evaluated using the systematically quantified fingerprint method (SQFM), and the 38 batches of samples were classified into two grades with good quality consistency. Quantitative analysis of the five markers of CLTs was performed simultaneously using the standard curve method (SCM) and the quantitative analysis of multiple components by single marker (QAMS). The results showed no significant differences between the two analytical methods (p > 0.5). In addition, the in vitro dissolution of CLTs in two media (pure water and pH = 4.5 medium) was determined by the total UV fingerprint dissolution assay. The similarity of the dissolution curves was also analyzed by combining the f2 factor and the dissolution-systematically quantified fingerprint method (DSQFM). The result showed that most of the samples had f2 > 50 and Pm satisfied the range of 70-130%. Finally, a principal component analysis (PCA) model was developed to combine the evaluation parameters of chemical fingerprint and dissolution curves for comprehensive analysis of the samples. In this study, a chromatographic and dissolution-based quality analysis method was proposed, which effectively overcomes the shortcomings of previous analytical methods and provides a scientific analytical method for the quality control of natural drugs.

Fabrication of timed-release indomethacin core-shell tablets for chronotherapeutic drug delivery using dual nozzle fused deposition modeling (FDM) 3D printing.

In the present study, timed-release indomethacin tablets, releasing drug after predetermined lag times, were developed for the effective treatment of early morning stiffness in rheumatoid arthritis using two-nozzle fused deposition modeling (FDM) 3D printing with a Bowden extruder. The developed core-shell tablets consisted of a drug-containing core and release-regulating shell with different designed thicknesses (i.e., 0.4 mm, 0.6 mm, 0.8 mm). The filaments to fabricate cores and shells were prepared using hot-melt extrusion (HME), and different filament compositions were formulated for core tablets and screened for rapid release and printability. Eventually, the HPMCAS-based formulation comprised a core tablet enclosed by a shell of Affinisol™ 15LV, a swellable polymer. During 3D printing, one nozzle was dedicated to printing core tablets loaded with indomethacin, and the other nozzle was dedicated to printing shells, making a whole structure produced at once without inconvenient filament change and nozzle cleanout. The mechanical properties of filaments were compared using a texture analyzer. The core-shell tablets were characterized for dissolution profiles and physical attributes (e.g., dimension, friability, hardness). SEM image indicated a smooth and complete surface of the core-shell tablets. The tablets showed 4-8 h of lag depending on the shell thicknesses and released most of the drugs in 3 h, regardless of the shell thicknesses. The core-shell tablets showed high reproducibility but exhibited low dimensional accuracy in the shell thickness. This study explored the suitability of using two-nozzle FDM 3D printing with Bowden extrusion for producing personalized chronotherapeutic core-shell tablets and discussed possible challenges that needed to be considered for a successful printing process using this technology.

An Innovative Approach for Formulation of Rutin Tablets Targeted for Colon Cancer Treatment.

The aim of this study was the improvement of rutin solubility along with targeting its release to colon for effective treatment of colon cancer. Five formulations of compression-coated tablets were prepared with the same core composition including rutin-polyvinyl pyrrolidone K30 solid dispersion (rutin-PVP K30 SD) but differ in being coated with either frankincense alone or different combinations of frankincense with gelatin. The superior formula was selected based on the in vitro drug release then further evaluated in terms of physical properties and in vivo performance in dogs using X-ray. Moreover, in vitro cytotoxicity of rutin, rutin-PVP K30 SD, frankincense, and a mixture of rutin-PVP K30 SD with frankincense in a ratio representing their concentrations in the selected formula was assessed against human colon cancer (HCT-116) cell lines using sulforhodamine B assay. The formula (F4) with the coat consisted of 65%w/w frankincense and 35%w/w gelatin achieved acceptable in vitro controlled drug release. In vivo X-ray in dogs confirmed that F4 tablet could remain intact in the stomach and small intestine until reaching the colon. In vitro cytotoxicity revealed that mixture of rutin-PVP K30 SD with frankincense was more effective in arresting cancer cell growth than rutin or frankincense alone. Moreover, stability studies revealed that F4 tablets were physically and chemically stable. Thus, improving rutin solubility using solid dispersion technique and formulating it into frankincense-based compression-coated (F4) tablets would be a successful approach for colonic delivery of rutin with potential of improving therapeutic efficacy.

Cross-talk between the RAS-ERK and mTOR signalings-associated autophagy contributes to tripterygium glycosides tablet-induced liver injury.

BACKGROUND AND AIMS: Drug-induced liver injury (DILI) remains a critical issue and a hindrance to clinical application of Tripterygium Glycosides Tablet (TGT) despite its favorable therapeutic efficacy in rheumatoid arthritis. Herein, we aimed to elucidate the molecular mechanisms underlying TGT-induced hepatotoxicity. METHODS: Chemical profiling of TGT was identified by UPLC-Q/TOF-MS/MS and its putative targets were predicted based on chemical structure similarity calculation. Following "DILI-related gene-TGT putative target" interaction network construction, a list of key network targets was screened according to nodes' topological importance and functional relevance. Both in vivo and in vitro experiments were performed to determine drug hepatotoxicity and the underlying mechanisms. RESULT: A total of 49 chemical components and 914 putative targets of TGTs were identified. Network calculation and functional modularization screened RAS-ERK and mTOR signalings-associated autophagy to be one of the candidate targets of TGT-induced hepatotoxicity. Experimentally, TGT significantly activated RAS-ERK axis, elevated the number of autophagosomes and the expression of LC3II protein, but reduced the expression of p62 protein and suppressed mTOR phosphorylation in the liver tissues of TGT-induced acute liver injury mice and chronic liver injury mice in vivo and AML12 cells in vitro. Moreover, TGT and mL-098 (an activator of RAS) co-treatment reduced AML12 cell viability via regulating autophagy and TGT-induced liver injury-related indicators more dramatically than TGT treatment alone, whereas Salirasib (an inhibitor of RAS) had an opposite effect. CONCLUSION: RAS-ERK-mTOR cross-talk may play a crucial role in TGT-induced hepatocyte autophagy, offering a promising target for developing novel therapeutics to combat TGT-induced hepatotoxicity.

Enhancing tabletability of high-dose tablets by tailoring properties of spray-dried insulin particles.

The oral delivery of proteins and peptides provides an attractive dosing option due to its high patient compliance. However, as oral formulations of such macromolecules require the addition of typically poorly compactable permeation enhancers, the compression behaviour in tableting processes can become challenging. In this study, we show that poor compression behaviour can be overcome by tailoring the properties of peptide or protein particles, especially in high-dose tablet formulations. Spray-dried particles with varying particle size and morphology were produced and characterized. The particles were then evaluated for tabletability in well- and poorly tabletable formulations. Tabletability was found to be enhanced most with small and non-hollow spray-dried insulin particles in both formulations. The enhancement was more pronounced in the poorly tabletable formulation than in the well-tabletable one. Thus, the API particle properties play a key role, when evaluating manufacturability of poorly tabletable formulations.

Deep residual network enabled smart hyperspectral image analysis and its application to monitoring moisture, size distribution and contents of four bioactive compounds of granules in the fluid-bed granulation process of Guanxinning tablets.

Bed collapse is a serious problem in a fluid-bed granulation process of traditional Chinese medicine. Moisture content and size distribution are regarded as two pivotal influencing factors. Herein, a smart hyperspectral image analysis methodology was established via deep residual network (ResNet) algorithm, which was then applied to monitoring moisture content, size distribution and contents of four bioactive compounds of granules in the fluid-bed granulation process of Guanxinning tablets. First, a hyperspectral imaging camera was utilized to acquire hyperspectral images of 132 real granule samples in the spectral region of 389-1020 nm. Second, the moisture content and size distribution of the granules were measured with a laser particle sizer and a fast moisture analyzer, respectively. Moreover, the contents of danshensu, ferulic acid, rosmarinic acid and salvianolic acid B of the granules were determined by using high-performance liquid chromatography-diode array detection. Third, ResNet quantitative calibration models were built, which consisted of convolutional layer, maxpooling layer, four convolutional blocks with residual learning function and two fully connected layers. As a result, the Rc2 values for the moisture content, granule sizes and contents of four bioactive compounds are determined to be 0.957, 0.986, 0.936, 0.959, 0.937, 0.938, 0.956, 0.889, 0.914 and 0.928, whereas the Rp2 values are calculated as 0.940, 0.969, 0.904, 0.930, 0.925, 0.928, 0.896, 0.849, 0.844, and 0.905, respectively. The predicted values matched well with the measured values. These findings indicated that ResNet algorithm driven hyperspectral image analysis is feasible for monitoring both the physical and chemical properties of Guanxinning tablets at the same time.

[Ginkgo biloba Ketone Ester Tablets with different release rates prepared by fused deposition modeling 3D printing technology].

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.

Comprehensive Evaluation of the Quality of Tripterygium Glycosides Tablets Based on Multi-Component Quantification Combined with an In Vitro Biological Assay.

Tripterygium glycosides tablets (TGTs) are widely used in clinical practice to treat rheumatoid arthritis and other autoimmune diseases, with significant beneficial effects but also high toxicity, necessitating rigorous quality evaluation and control. In current study, a rapid resolution liquid chromatography tandem electrospray ionization triple quadrupole mass spectrometry (RRLC-ESI-MS/MS) method was developed and validated for the quantitative analysis of 14 components of ten batches of TGTs produced by different manufacturers, including four diterpenoids, three triterpenoids, and seven sesquiterpene alkaloids. Meanwhile, the NO inhibition effects of these TGTs were evaluated in LPS-induced RAW264.7 cells for their downstream anti-inflammatory activities, as well as their cytotoxicity. The results indicate that the TGTs from different manufacturers showed poor quality consistency, as evidenced by large variations in chemical profiles and biological effects, which may increase the risks associated with clinical use. To improve the quality status of TGTs, it is crucial to identify indicator components whose characterization can accurately reflect the efficacy and toxicity of TGTs from which they were derived. Our study reveals that triptolide, triptoquinone B, celastrol, and demethylzelaysteral considerably contributed to the anti-inflammatory activity and/or cytotoxicity of TGTs, implying that they should be further investigated as candidate indicator components for TGT quality control.

A Novel Preparation Method for Effervescent Tablets of Xianganfang Containing Fresh Juice using a Semi-Solid Extrusion 3D Printer with Three Cartridge Holders.

This study aimed to prepare effervescent tablets of traditional Chinese medicine Xianganfang with fresh juice using a semi-solid 3D printer with three cartridge holders to seperate acid and alkali source by drug paste through model design to avoid sticking impact and premature effervescence during the tableting in the conventional preparation process. The powder of Xianganfang including fresh juice of Phyllanthus emblica and licorice extract was obtained by vacuum freeze-drying with 50% mannitol as cryoprotectant. Then, the formulation of 3D-printed effervescent tablets was investigated. Further 5% HPMC hydroalcoholic gel was mixed with sodium bicarbonate and freeze-dried Xianganfang powder to prepare alkali source and drug paste respectively while 30% PVP ethanol solution was mixed with tartaric acid to prepare acid source paste; these three pastes had good printability. The pastes of drug, acid, and alkali were loaded into three syringe cartridges separately and numbered as "3," "5," and "7," according to cartridge holders of the 3D printer, and printed in the order of "537,353,735" for separating acid and alkali by drug to avoid premature effervescence. And the basic printing parameters were optimized. The tablets were evaluated by the appearance, tablet weight variation, hardness, disintegration time, friability, pH, and stability. The physicochemical properties all conformed to the Chinese Pharmacopoeia 2020 edition. The content of the active ingredient gallic acid was 0.769 ± 0.019 mg/g. This study provided a new method to prepare effervescent tablets of traditional Chinese medicine with fresh juice using 3D printing technology.

A new direct compression mechanism of structural transition in Poria cocos extract composite particles.

The structural transition to generate amorphous translucent grains in Poria cocos dry extract (PCE) composite particles was found and studied as a new direct compression mechanism. The pressure and displacement sensing techniques were used to obtained stress-strain profiles during compression. The Exponential function, Kawakita model, Shapiro model and Heckel model were used to analysis mechanical properties of powders. 12 parameters derived from compression models and powder physical properties were applied to partial least squares method (PLS) for analyzing powder compression mechanism. It was found that only the oven-dried PCE composite particles undergoes the structural transition and generate translucent grains scattered and embedded in tablet, and these tablets have excellent mechanical stability. The structural transition in plant dry extract as the PCE composite particles could be exploited to improve powder compression and tabletability.

An integrated strategy to delineate the chemical and dynamic metabolic profile of Huachansu tablets in rat plasma based on UPLC-ESI-QTOF/MSE.

Metabolic research is a key method to understand the fate of traditional Chinese medicine (TCM) prescription in vivo and help to explain its pharmacological effects. Huachansu (HCS) tablets are prepared from the dried skin of Bufo gargarizans (Cantor, 1842), which have the effects of detumescence and analgesia, and used in the treatment of middle and advanced tumors. However, an in-depth understanding of the chemical components of HCS tablet and its metabolism in vivo is lacking. In this study, an integrated analytical strategy based on UPLC-ESI-QTOF/MSE was developed to efficiently identify the chemical components, the absorbed prototype compounds and metabolites of HCS tablets given by gavage in rats, and track their dynamic changes. As a result, 77 chemical components of HCS tablets were characterized, including 46 bufadienolides, 11 alkaloids, 10 amino acids and organic acids, 9 nucleosides, and 1 other component. Further more, 16 prototype compounds and 47 metabolites (38 bufadienolides-related and 9 alkaloids-related) were identified in rat plasma. Through the dynamic detection of prototype compounds and metabolites of HCS tablets in vivo, the phenomenon that 3 prototype compounds and 16 metabolites reappeared after a period of disappearance from the plasma was found. Additionally, 8 prototype compounds with large intensity in HCS tablet samples were not detected in the plasma samples of rats given HCS tablets but had metabolites within 0-24 h after administration, indicating that these components were rapidly absorbed and metabolized into metabolites in vivo. It was also observed that 9 metabolites can be driven from various prototype compounds and reach high concentrations in a short time. This study comprehensively identified the xenobiotics and metabolites of HCS tablets in rat plasma sample, systematically discussed their dynamic metabolic process in vivo, which laid a foundation for studying the pharmacodynamic substances of HCS tablets.

Identification and comparison of compounds in commercial Tripterygium wilfordii genus preparations with HPLC-QTOF/MS based on molecular networking and multivariate statistical analysis.

Tripterygium wilfordii genus preparations (TWGP) are widely used in traditional Chinese medicines for the treatment of autoimmune diseases and immune diseases with definite therapeutic effects but high toxicity. The aim of this study is to identify and compare chemical compounds in three types of commercial TWGP using UHPLC-QTOF-MS/MS and molecular networking (MN) technology. First, the mass fragmentation pathways of 10 compounds were investigated, which included two sesquiterpene alkaloids, four diterpenoids, and four triterpenoids. The chemical compounds were then identified using UHPLC-QTOF-MS/MS and a conventional database. Following that, molecular network technology was used to further identify the GNPS platform. Finally, metabonomic data analysis was used to compare 92 commercial TWGP samples from 13 manufacturers. A total of 103 compounds were identified, with the molecular network detecting 40 of them. Moreover, the quality of commercial Tripterygium glycoside tablets varies greatly and 26 compounds, including triptolide, wilforine, wilforgine, and demethylzeylasteral, were discovered to be the main differential compounds in tripterygium glycosides tablets. This was the first time MN technology was used for compound analysis in TWGP, laying the foundation for classifying effective and toxic substances and TWGP quality control.

Improvements on multiple direct compaction properties of three powders prepared from Puerariae Lobatae Radix using surface and texture modification: Comparison of microcrystalline cellulose and two nano-silicas.

It has been reported that hydrophilic nano-silica (N) markedly improved direct compaction (DC) properties of Zingiberis Rhizoma alcoholic extract. This study aims to examine the broader scope and generality of the previous work by investigating (i) three powders, i.e., the directly pulverized product, ethanol extract, and water extract prepared from the same medicinal herb-Puerariae Lobatae Radix (named DP, EE, and WE) and (ii) the effects on their DC properties of co-processing with N, hydrophobic nano-silica (BN), or microcrystalline cellulose (C). Unexpectedly, C provided the best improvement on tabletability for WE, while N for both DP and EE. More importantly, only N could move all parent powders to a regime suitable for DC, and BN rather than C enabled parent WE to be directly compressed. Typically, 6/9 N-modified powders simultaneously met the requirements of DC on bulk density, flowability, and tablet tensile strength (σt). Principal component analysis indicated that DC properties were mainly governed by flowability and texture properties. The partial least-squares regression model revealed that flowability, texture parameters, and deformation behavior of powders were dominating factors impacting tablet σt and solid fraction. Overall, the findings are promising for the manufacture of high drug loading tablets of herbs by DC.

Comprehensive chemical profile and quantitative analysis of the Shabyar tablet, a traditional ethnic medicine prescription, by ultra-high-performance liquid chromatography with quadrupole-orbitrap high-resolution mass spectrometry.

The Shabyar tablet is commonly used as a traditional ethnic medicine prescription for the treatment of night blindness, poor vision, and headaches. However, the chemical components of the Shabyar tablet have not been holistically explored, which seriously hinders the discovery of the activity. This study qualitatively and quantitatively investigated the overall chemical profile of the Shabyar tablet using ultra-high-performance liquid chromatography hyphenated with quadrupole-orbitrap high-resolution mass spectrometry. Altogether, 170 chemical components, including 59 flavonoids, 78 organic acids, 12 anthranones, three anthraquinones, one naphthalene, and 17 other compounds were tentatively identified and attributed, with 40 among these being unambiguously characterized in comparison with their corresponding authentic standards. To further determine the major representative constituents of the Shabyar tablet, a quantitative method was used for the simultaneous analysis of 33 characteristic components in Shabyar samples. The results were validated in terms of linearity, precision, repeatability, stability, and recovery. This newly developed approach could be successfully employed for evaluating the holistic quality of crude extracts and Chinese medicines in the Shabyar compound tablet and provide a solid chemical foundation for additional investigations on in vivo pharmacodynamics and therapeutic mechanisms to identify the potential effective components of traditional medicines.

Utilization of Pectin from Okra as Binding Agent in Immediate Release Tablets.

Polymeric materials from plants continue to be of interest to pharmaceutical scientists as potential binders in immediate release tablets due to availability, sustainability, and constant supply to feed local pharmaceutical industries. Paracetamol tablet formulations were utilized in investigating the potential binding characteristics of pectin harnessed from various okra genotypes (PC1-PC5) in Ghana. The pectin yields from the different genotypes ranged from 6.12 to 18.84%w/w. The pH of extracted pectin ranged from 6.39 to 6.92, and it had good swelling indices and a low moisture content. Pectin extracted from all genotypes were evaluated as binders (10, 15, and 20%w/v) and compared to tragacanth BP. All formulated tablets (F1-F18) passed the weight uniformity, drug content, hardness, and friability tests. Based on their crushing strength, tablets prepared with pectin from the various genotypes were relatively harder (P ≤ 0.05) than tablets prepared with tragacanth BP. Tablets prepared with pectins as binders at 10%w/v and 15%w/v passed the disintegration and dissolution tests with the exception of PC4 at 15%w/v. Incorporation of pectin from all genotypes (excluding PC5) as a binder at concentrations above 15%w/v (F13, F16, F14, and F15) produced tablets which failed the disintegration test and showed poor dissolution profiles. Thus, pectin from these genotypes can be industrially commodified as binders in immediate release tablets using varying concentrations.