OBJECTIVE To investigate the impact of polyethylene oxide (PEO, POLYOX^TM), penetration additives, and butylated hydroxytoluene (BHT) on tablet properties and drug release of mirabegron extended release (ER) tablets and provide some ideas of formulating polyethylene oxide based ER tablets for the formulators. METHODS Single-factor-experiment was applied to investigate the impact of formulation components on drug release of mirabegron ER tablets. Different molecular weight (MW), series of particle size and use level of polyethylene oxide, three types of penetration additives (PEG 8000, PEG 4000 and lactose) and several use levels of butylated hydroxytoluene (BHT) were investigated. RESULTS Mirabegron ER tablets formulated with polyethylene oxide WSR N60K at 28% use level got statistically equivalent drug release with marketed mirabegron ER tablets. Higher MW and higher use level of polyethylene oxide led to slower drug release, while lower MW and lower use level led to faster drug release. Particle size of polyethylene oxide WSR N60K did not significantly affect mirabegron drug release. The tablets using either polyethylene glycol (PEG 8000 or 4000) or lactose as penetration additives could achieve equivalent drug release as marketed mirabegron ER tablets. The blend of polyethylene oxide WSR 301 and N12K at ratio of 35∶65 has the same viscosity with polyethylene oxide WSR N60K and led to statistically similar drug release. CONCLUSION Formulation of polyethylene oxide based mirabegron ER tablets are robust.

Nano quantity analyte detector (NQAD) is a universal detector based on the principle of aerosol developed in recent years. The detector response is not dependent on the chemical structure of the analyte, but only on the size and quantity of aerosol particles. With the characteristic of wide range of linearity, high sensitivity, simplicity of calculation, operation and stable, NQAD is suitable for those analytes of non-ultraviolet absorption, difficult ionization, non-electrochemical activity, which makes up for the deficiencies of other detectors. In this paper, the operating principle, characteristics, and advantages of NQAD and its application in pharmaceutical analysis are reviewed, and the application in drug quality control is prospected.

OBJECTIVE To analyze the influencing factors of tacrolimus (FK506) blood concentration non-attainment in renal transplant patients and construct a risk prediction column-line diagram model. METHODS Two hundred patients admitted to the hospital from June 2020 to June 2023 who were treated with FK506 after renal transplantation and whose blood concentration was monitored for 30 d were selected for the study, and according to the monitoring results, they were categorized into 126 cases in the group of meeting the standard (5-15 μg·L^-1) and 74 cases in the group of failing to meet the standard (<5 μg·L^-1 or>15 μg·L^-1), and the clinical data were collected, and independent risk factors for failing to meet the standard of FK506 were screened and fit into a predictive model by single-factor and multifactorial logistic regression analysis. Clinical data of the two groups were collected, and the independent risk factors for FK506 blood concentration non-compliance were screened by single-factor and multifactor logistic regression analyses, according to which, a prediction model for the risk of FK506 blood concentration non-compliance was constructed with a line graph and tested for goodness-of-fit. RESULTS Of the 1 200 FK506 concentration monitoring sessions in 200 patients within 30 d after surgery, the number of sessions in which the target concentration of 5-15 μg·L^-1 was reached was 756, with an attainment rate of 63.0%. A total of 126 patients reached the target concentration (target group), and 74 patients did not reach the target concentration (non-target group). The proportion of patients with age >60 years, male, intravenous, fasting blood glucose (FPG) >7 mmol·L^-1, total bilirubin (TB) >20 μmol·L^-1, white blood cell count (WBC)≤4×10⁹·L^-1, and blood creatinine (Cr) >133 μmol·L^-1 was higher in the non-attainment group than in the attainment group, and the difference was statistically significant (P<0.05). Multifactorial logistic regression analysis was performed, and the results showed that age >60 years, male, FPG>7 mmol·L^-1, TB>20 μmol·L^-1, and Cr>133 μmol·L^-1 were independent risk factors for substandard FK506 blood concentration in renal transplant patients (all P<0.05). The AUC of the constructed column-line graph model reached 0.859 (0.795-0.924), the model calibration curve validation C-index was 0.836, and the H-L deviation test χ²=4.203, P=0.516, the calibration curve was basically the same as the ideal curve trend, with a good degree of precision and differentiation. DCA analysis showed that the column-line graph prediction model displayed a large range of threshold probabilities (0.05 to 0.95), which corresponded to the largest area of the red curve to the gray curve and the horizontal axis, indicating a better clinical utility value of the model. CONCLUSION Age >60 years, male, FPG >7 mmol·L^-1, TB >20 μmol·L^-1, and Cr >133 μmol·L^-1 are the risk factors for substandard FK506 blood concentration in renal transplantation patients, and the column-line graph model constructed accordingly can effectively predict the degree of risk for substandard FK506 blood concentration in renal transplantation patients.

Central nervous system (CNS) diseases are a serious threat to human health. However, due to the existence of blood-brain barrier (BBB), there is a lack of effective technology to deliver drugs to the brain, which seriously affects the success rate of drug development related to CNS diseases, resulting in treatment results that are often unsatisfactory. Therefore, a new technology is urgently needed to solve the above problems. Brain targeted peptide-drug conjugates, which consist of a brain targeted peptide, a linker, and a payload, have become a promising CNS drug by enabling bioactive molecules to cross the BBB and reach the brain parenchyma by using biologically relevant endogenous transport mechanisms. In this review, the types and characteristics of brain targeting peptides, linkers, and payloads are briefly introduced, and some common brain targeting peptide-drug conjugates are listed, as well as the challenges faced by such drugs and the improvement methods, in order to provide ideas for the design and development of drugs for CNS diseases.

OBJECTIVE To explore the mechanism of Atractylodes macrocephala polysaccharide (AMP) in improving chronic unpredictable mild stress (CUMS) depression in mice by integrating metabolomics technology and gut microbiota analysis. METHODS CUMS depression mouse model was established. Low, medium and high dose AMP treatment were given at 0.062 5, 0.125, 0.250 g·kg^-1, respectively, fluoxetine was given at the dosage of 0.015 g·kg^-1, control group and model group were given 0.9% saline solution, and all groups were given at 5 mL·kg^-1·d^-1 of drug. The content of 5-hydroxytryptamine(5-HT) in the brain of mice was determined by enzyme-linked immunosorbent assay (ELISA), and the CUMS depression model was tested by combining sucrose preference test (SPT) results. The 16S rDNA amplicon sequencing technology was used to analyze the gut microbiota in the feces of mice in each group. LC-MS technology was used to perform non-targeted metabolomics determination of mouse serum. RESULTS Compared with the control group, the sucrose preference rate of CUMS model mice was significantly lower, and the content of 5-HT in the brain of mice was significantly reduced (P<0.01), indicating that the CUMS depression model was successfully established. After AMP treatment, the sucrose preference rate and 5-HT content of mice in each group increased (P<0.01), the gut microbiota of CUMS mice had a regulatory effect, serum metabolites were significantly changed, and 58 metabolites were significantly adjusted. Spearman correlation analysis showed that the changes in gut microbiota were significantly associated with the changes in metabolite levels. CONCLUSION AMP exerts intervention effects on CUMS depression model mice by regulating the stability of gut microbiota, upregulating the F-B ratio, and thereby regulating metabolic pathways.

OBJECTIVE To establish the fingerprint and content determination method of Impatientis Pritzelii Rhizoma to improve the quality control method of Tujia ethnomedicinal herb Impatientis Pritzelii Rhizoma. METHODS The fingerprint was established by UPLC with ACQUITY UPLC BEH C₁₈ column. Phlorizin content assay was performed by HPLC with Eclipse XDB-C₁₈ column. The mobile phases for both methods were composed of acetonitrile and 0.1% formic acid with different gradient elution procedures. The detection wavelength was set at 283 nm. The comparative study was carried out between Impatientis Pritzelii Rhizoma and its adulterants (such as the roots and rhizomes of Impatiens pinfanensis, I. uliginosa, I. siculifer and I. noli-tangere). RESULTS Nine main chromatographic peaks in the fingerprint could be served as the characteristic peaks of Impatientis Pritzelii Rhizoma, four of which were corresponding to catechin, epicatechin, scopolamine and phlorizin, respectively. The established fingerprint could reflect the distribution of the chemical components of Impatientis Pritzelii Rhizoma, which was distinguished from four adulterants. Phlorizin was found and determined in Impatientis Pritzelii Rhizoma for the first time. The contents in 16 batches of Impatientis Pritzelii Rhizoma ranged from 0.007% to 0.085%, while no phloridin was found in the adulterants. CONCLUSION The established methods for the fingerprint and phlorizin content determination of Impatientis Pritzelii Rhizoma are specific, accurate and effective, which could be used for its quality control.

OBJECTIVE To establish a high performance liquid chromatography-refractive index detector method for the determination of main potential carbohydrate residues fructose and sucrose concentration in dextran 40 raw materials from different of production processes, analyze the differences in carbohydrate residues in dextran 40 produced by different manufactures, and provide a reference for the quality evaluation of related drugs and the formulation or edit of national drug standards. METHODS Isocratic elution was performed on a ZORBAX-NH₂ column. Mobile phase consisted of 75% acetonitrile and 25% water at a flow rate of 1.0 mL·min^-1. RID was used as detector. The detector temperature and column temperature was maintained at 40 ℃ and the injection volume was 50 μL. RESULTS Sucrose was not detected in all batches of dextran 40. Fructose residue could only be detected in dextran 40 which using alcohol precipitation production process, and the content was 0.005%-0.14%. No fructose residue was detected in the dextran 40 of manufacturer B using membrane filtration method. CONCLUSION The HPLC-RID method is established to determine the content of fructose and sucrose in dextran 40. The method has strong specificity, high sensitivity, good stability and simple operation. The amount of fructose residual in dextran 40 produced by different processes varies greatly. The fructose residual in the raw material of dextran 40 obtained by membrane filtration is significantly lower than that by alcohol precipitation, it is necessary to control the fructose residue in the quality standard.

Hippophae rhamnoides L. is a high-quality medicinal and edible plant with rich nutritional values and a wide range of biological activities. It has been used to improve hyperglycemia, hyperlipidemia, liver injury and prevent cardiovascular diseases. Sea buckthorn polysaccharides (SBPs) are one of the most important bioactive components of Hippophae rhamnoides L.. The preperation methods of SBPs include hot water extraction, ultrasonic-assisted extraction, microwave-assisted extraction, and flash extraction. Different preperation methods lead to different configurations and biological activities of SBPs. Furthermore, these biological activities are related to the chemical structure of SBPs, including the relative molecular weight, monosaccharide composition, glycosidic bond and three-dimensional structure. Modern pharmacological studies have demonstrated that SBPs possess various activities, including hepatoprotective, anti-inflammatory, immunomodulatory, anti-tumor, antioxidant activity, as well as the regulation of blood sugar and lipid metabolism disorder, which will exhibit excellent development value in functional food and medicament. However, few studies on the structure-function relationship of SBPs have been reported. In this paper, the preperation methods, structure characterization, pharmacological activities and the utilization of SBPs were systematically reviewed, the structure-activity relationship and application prospect were discussed, which will provide a theoretical basis for a further research and development and utilization of SBPs.

OBJECTIVE To analyze the chemical components of Longzuan Tongbi Granules, a classical prescription of Zhuang medicine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS The MS/MS data were collected in positive and negative ion mode after gradient elution of the test solution using an ACQUITY UPLC HSS T3 column (2.1 mm×100 mm, 1.8 μm) and a mobile phase system consisting of 0.1% formic acid water (A)-0.1% formic acid acetonitrile (B). RESULTS A total of 113 compounds, including 64 alkaloids, 20 flavonoids, 12 organic acids, 8 coumarins, 5 lignans and 4 others, were identified by high-resolution mass spectrometry data analysis, reference substance and database comparison, while referring to the mass fragmentation patterns of relevant components reported in the literature, and of which 109 secondary metabolites were attributed for recognition. CONCLUSION The material basis of Longzuan Tongbi Granules is rich, represented by alkaloids, and Toddalia asiatica is the important “main drug”. This information can provide a scientific basis for the pharmacodynamic mechanism study and rational clinical use of this formula.

OBJECTIVE To prepare a “sandwich” oral film (composed ofthe backing layer, sustained release layer, and adhesion layer) containing triamcinolone acetonide for the treatment of oral ulcers. METHODS Triamcinolone acetonide oral film was prepared by a tape casting process using ethyl cellulose (EC), hydroxypropyl methylcellulose (HPMC), and polyacrylic acid (PAA) as carrier materials. Taking the appearance, thickness, uniformity, adhesion, and mechanical strength of the film as indicators, the formulation of the backing layer, sustained release layer, and adhesion layer was optimized by a single factor study. The film's physicochemical properties and drug release in vitro were compared with the commercially available formulation Taisho^®. RESULTS The drug loading of the resulting triamcinolone acetonide three-layer oral film was 96.0%, and the film had good uniformity, mechanical strength, and adhesion. The designed oral film had a release curve similarity factor f₂ of 54.25 when compared to the commercially available formulation of Taisho^®. CONCLUSION The quality of triamcinolone acetonide oral film prepared by the tape casting process is consistent with that of Taisho^®. Moreover, the technology of this film is simple and feasible, with the potential for industrial conversion.