Solvent-free styrene-isoprene-styrene(SIS) block copolymer-based hot melt pressure sensitive adhesive(HMPSA) is commonly used as transdermal patch matrix due to its advantages of environmental protection, high adhesion strength and good drug compatibility. However, the aging problem in its long-term storage and use will lead to problems such as viscosity attenuation and abnormal drug release, which restricts its clinical application and industrialization promotion. This paper mainly introduces the material properties, aging types and mechanisms of solventfree SIS-based HMPSA, systematically summarizes the aging characterization techniques and evaluation methods, and the current commonly used anti-aging strategies. Based on the existing research progress, this paper analyzes the advantages and limitations of different strategies, and puts forward the future research direction, aiming to provide a reference for the development of anti-aging properties of HMPSA for transdermal patches.

Erdafitinib(1), a novel small-molecule targeted agent, is the first fibroblast growth factor receptor(FGFR) tyrosine kinase inhibitor approved for the treatment of advanced or metastatic bladder cancer. By selectively targeting genetic alterations in FGFR signaling pathways(such as mutations, fusions, or amplifications), it modulates cellular growth and division, thereby treating urothelial carcinoma of bladder and demonstrating broad clinical and commercial application prospects. This review systematically analyzes the synthetic strategies of 1, comprehensively reviews 9 reported synthetic routes of 1, and critically evaluates the advantages and limitations of each route. These abovementioned insights aim to offer valuable references and guidance for the synthesis research and industrial-scale manufacture of 1 and its key intermediates.

Enteral tube administration is an important oral alternative treatment route for patients with dysphagia. However, its clinical application faces multiple challenges, such as insufficient standardization, lack of guidance in drug package inserts, and an immature in vitro evaluation system. The U.S. FDA has issued enteral tube administration technical guidelines for more than 30 types of drugs(e.g., esomeprazole capsules, rivaroxaban tablets), clearly specifying test parameters(including enteral tube diameter, types and volumes of dispersion medium, incubation time). Currently, the problem of missing or incomplete information related to enteral tube administration in the package inserts of generic drugs in China is prominent, which may lead to clinical operation errors and risks to drug stability. This article reviews the relevant technical guidelines for enteral tube administration, the current status and research progress of clinical applications at home and abroad, as well as the existing problems. It focuses on summarizing the key points to be noted when conducting in vitro comparative studies, aiming to provide technical suggestions for the design, implementation, and result evaluation of in vitro tests for oral drugs administered via enteral tubes.

An optimized synthetic route for mirogabalin besylate(1), a drug for the treatment of diabetic neuropathic pain in adults, was developed using 3-ethylbicyclo[3.2.0]hept-3-ene-6-one(2) as the starting material. The process involved chemical resolution, Wittig-Horner reaction, Michael addition, nitro reduction, secondary resolution, deprotection, and salt formation. In this optimal route, key improvements included enhancing the chiral resolution method and optimizing the nitro reduction step, which mitigated safety risks from Raney nickel hydrogenation. The overall yield increased from 8％ to 10.2％ (based on 2), with HPLC purity of the targeted compound reaching 99.2%. Featuring simple operation and reliable product quality, this route is suitable for industrial production.

Sevoflurane(1) is a widely used inhalation anesthetic. To address the issues in existing synthetic techniques, this study developed the continuous gas phase synthesis of 1. Using Cr-Ce@C as the catalyst and hexafluoroisopropyl chloromethyl ether and hydrogen fluoride as raw materials, the gasified and mixed reactants flowed into the catalytic bed for a fluorine-chlorine exchange reaction. After 33 min of operation, the conversion rate of chloromethyl ether and the selectivity for 1 reached 92％ and 97％ , respectively. The isolated yield of target product 1 was 80％ with a purity of 99％ . This method demonstrated excellent selectivity, safe control, and showed significant potential for continuous large-scale production and automated process control.

To further improve the applicability of production process and safety of production operations, this study established a chromatography method without ethanol or phenol for the preparation of pneumococcal polysaccharides. With the process control capability(including the recovery ability of the target substance and the impurity removal effect) and crucial quality attributes of the product as the main evaluation indicators, this study confirmed the crucial process parameter as follows: ultrafiltration cassettes with a molecular weight cut-off of 100 000, ultrafiltration dialysis multiples ≥ 20, hexadecyl trimethyl ammonium bromide mass fraction of 1.0 ％ (3.0％ for pneumococcal polysaccharide type 23F), chromatography buffer pH value of 6.7 - 7.1. In compliance with the commercial production scale, the chromatography method was used to isolate and purify pneumococcal polysaccharides. The quality of the pneumococcal polysaccharides prepared by the chromatography method is in line with the standards of ChP 2020 Edition. And the polysaccharides exhibited good stability over 60 months. It indicated that the established process were stable and reliable, providing a technical support for the commercial-scale production of pneumococcal polysaccharide.

To improve the dissolution and bioavailability of poorly soluble drugs, a novel drug delivery system based on periodic mesoporous organosilicas(PMOs) was proposed. The PMOs carriers were synthesized via a hydrothermal method using 1,2-bis(triethoxysilyl)ethane(BTEE) as the bridged organosilica precursor. The poorly soluble drug fenofibrate(1) was loaded onto the carriers to obtain the drug delivery system, 1/PMOs. The the carrier structure, in vitro dissolution and in vivo bioavailability of the drug were investigated. The results showed that the PMOs exhibited a uniform mesoporous structure with a pore size of 3.65 nm, and the pore walls were composed of an organic-inorganic hybrid amorphous framework containing ethane groups. Compared with the bulk drug 1, 1/PMOs significantly increased the in vitro dissolution rate of drug, achieving over 90％ dissolution within 5 min. In vivo pharmacokinetic studies in rats demonstrated that the relative bioavailability of 1/PMOs was increased to 800％ of that of the 1 suspension. This enhancement could be attributed to the high specific surface area of the carrier, which allowed the drug to be highly dispersed and physically adsorbed within the ordered mesopores. Due to the limitations of the pore channels, the drug remained in a water-soluble amorphous state, thereby accelerating its dissolution in the gastrointestinal tract and improving its in vivo absorption. This strategy effectively solves the low oral bioavailability of 1.

The overfill volume of monoclonal antibody injections significantly affects drug quality, production costs, and clinical safety, making it a critical consideration during drug development, production, and regulatory review. This study used Osemitamab monoclonal antibody injection(labeled as 7.5 mL) as the object. The properties of the drug solution were determined by viscosity and density measurements, and hold-up volume tests were conducted by simulating clinical operations(n=90). The upper control limit(UCL) for the variability of hold-up volume of penicillin bottles and syringes was determined to be 0.39 mL using statistical process control chart analysis. Based on the accuracy of the filling production line(with a variability of 2％ ), the excess filling volume was calculated to be 0.54 mL, the target filling volume was 8.04 mL, and the filling volume control range was 7.89 - 8.19 mL. Compared with the traditional method(target filling volume of 8.22 mL), the optimized method can save 2.2％ of the drug solution and significantly reduce production costs, which provided practical guidance and references for the formulation of biological product filling strategies.

A HPLC-charged aerosol detector(CAD) method based on hydrophilic interaction chromatography(HILIC) mode was established for the determination of related substances and content of voglibose in bulk drug. An Agilent InfinityLab Poroshell 120 HILIC-Z column(3.0 mm×150 mm, 2.7 μm) was used, with 200 mmol/L ammonium formate solution(pH 3.0 adjusted with formic acid) and acetonitrile (250 ∶ 750) as the mobile phase. The flow rate was 0.5 mL/min, the column temperature was 50 ℃. The temperature of the CAD was 50 ℃, the data acquisition frequency was 2 Hz, and the filtration constant was 3.6 s. The methodological research results showed that the separation between the main component and various impurities was good, and there was a good linear relationship of the main component and various impurities in the corresponding mass concentration ranges. The average recoveries of three known impurities (n=9) were 103.0％ , 99.0％ , and 95.6％ , with RSD of 4.1％ , 5.6％ , and 4.2％ , respectively. The average recovery of main component(n=9) was 100.0％ , with RSD of 1.1％ . The detection limits for voglibose and its impurities Ⅰ , Ⅱ , Ⅲ were 1.3, 2.6, 3.3, and 1.5 ng, respectively. This method is easy to operate and has high specificity, which can provide a reference for the quality control research of strongly polar compounds without ultraviolet absorption.

A UPLC-MS/MS method was established for the determination of nitrosamine drug substance-related impurities(NDSRIs), 2-(1-nitrosopiperidin-4-yl)-1H-benzo[d]imidazole(2) and 1-(2-ethoxyethyl)-2-(1-nitrosopiperidin4-yl)-1H-benzo[d]imidazole(3) in bilastine(1). A Hypersil Gold column(2.1 mm×100 mm, 3 μm) was used with 0.1％ formic acid solution as mobile phase A and acetonitrile as mobile phase B under linear gradient elution conditions. Mass spectrometry was performed using an electrospray ionization(ESI) source in positive ion mode with selective reaction monitoring(SRM) for detection. The results showed that good linear relationships were obtained for 2 and 3 in the range of 0.2 - 4.0 ng/mL. The limits of quantification were 0.020 6 and 0.021 0 ng/mL, and the limits of detection were 0.006 2 and 0.006 3 ng/mL, respectively. The average recoveries(n=9) were 100.98％ and 101.25％ , with the RSDs of 0.95％ and 1.25％ , respectively. This study can provide a reference for the NDSRIs control of 1.

The applicability of culture media after 4-hour exposure for dynamic monitoring of settling microbes in cleanrooms was validated in this study. Referring to the technical requirements of Appendix Ⅰ of “Good Manufacturing Practice (2010 Revision)”(GMP) and Chinese Pharmacopoeia 2020 Edition(ChP 2020) Part Ⅳ , General Chapter 9205, six groups of 40 prefilled plates(with 90 mm diameter) containing tryptic soy agar(TSA) were separately exposed in a biosafety cabinet for 30 min and 4 h, respectively. After exposure, the plates were weighed to calculate water loss rate, and media applicability was validated using the spread plate method in accordance with the ChP 2020 General Chapter 1105. The results showed that under the conditions of temperature of 17 - 26 ℃ , relative humidity of 12％ - 63％ , descending airflow velocity of 0.32 - 0.33 m/s, and inflow airflow velocity of 0.54 - 0.56 m/s, the maximum water loss rate of the medium was 27.84％ , and the recovery ratios of all tested bacteria ranged from 0.5 to 2.0. This study confirmed that the 4-hour exposure of culture medium for dynamic monitoring of settled plates in cleanrooms met the requirements of General Chapter 1105 of the ChP 2020 .

To develop the cleaning procedure for in situ cleaning(CIP) of solution preparation unit in biopharmaceutical production, this study optimized the process in two phases. In the first phase, the water storage step for water for injection cleaning in the original procedure was eliminated. After cleaning 5 tanks and pipelines, full inspections were performed on the collected samples. Subsequently, microbial limit tests were conducted daily for 3 consecutive days, and this entire process was repeated for 3 rounds. The minimum value of the post-cleaning hold time across the 3 rounds was defined as the post-cleaning hold time. In the second phase, the optimized procedure was divided into two CIP processes: post-production CIP(pre-cleaning with purified water + alkaline cleaning) and the pre-production CIP(cleaning with purified water + water for injection). Representative tanks and the most difficult-to-clean components were selected. Sampling and testing were carried out after adhering to the preset dirt hold time, alkaline hold time, and post-cleaning hold time. This phase was repeated for 2 rounds. Finally, the key parameters of the cleaning process(including the CIP procedure, pre-cleaning hold time, alkaline hold time, and post-cleaning hold time) were determined for use in the concurrent cleaning validation during production.