Tucatinib(1) is an oral inhibitor of HER2 for clinical treatment of HER2- positive breast cancers. In this paper, the synthesis methods of 1 and its key intermediate 4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3- methylaniline(2) are reviewed, and the advantages and disadvantages of each synthetic route are discussed. This review is beneficial to the future process research of tucatinib.

This paper summarizes the relevant literature on tablet disintegration published at home and abroad from 2010 to 2021, and outlines the influencing factors and possible disintegration mechanisms of tablet disintegration process. The disintegration of tablets is affected by the properties of raw and auxiliary materials, formulation composition, process parameters and disintegration medium. The mechanisms of tablet disintegration mainly include swelling, shape recovery and wicking. Among the commonly used functional auxiliary materials for disintegration, starch and its derivatives, croscarmellose sodium and sodium carboxymethyl starch promote disintegration through swelling. The mechanism of polyvinylpolypyrrolidone promoting disintegration is shape recovery. Cellulose and its derivatives promote disintegration through strong wicking effect. Future research directions include: correlation modeling between critical material attributes, critical process parameters and tablet disintegration behavior in tablet technology; objective, visual and quantitative characterization of tablet disintegration process and behavior; development and application of new pharmaceutical excipients to promote tablet disintegration.

Lignin is a kind of natural aromatic biopolymer, which is usually composed of highly cross-linked aromatic ether unit structures through random polymerization. It is a widely distributed and high-yield biomass resource, inferior to cellulose and hemicellulose. It is expected to become an important and inexpensive source of aromatics, which is crucial for the pharmaceutical field. This paper reviews the current extraction methods, degradation technologies of lignin, and summarizes the applications of lignin and its degradation and modification products in the pharmaceutical field, so as to provide some references for the full utilization and functional application of lignin resources.

The U.S. FDA approved 53 new drugs in 2023, including 31 chemical small molecules, 21 biological products and 1 botanical drug. According to the prescription information for professionals and the related literature as well as patent information, this review describes the descriptions, indications, mechanism of action, dosage forms and strengths, adverse reactions, and one synthetic route of the chemical small molecules, and brief information about biological and botanical products.

Dynamic vapor sorption(DVS) technology is served as a crucial tool for the examination of pharmaceutical crystal forms and co-crystals. Not only can DVS technology assess moisture sorption performance of an API, but it also probes into phase transition issues, co-crystal screening, quantification of amorphous content at low levels in crystalline materials, as well as the miscellaneous. At present, many countries and regions have included DVS technology into their pharmacopoeias for the exploration of water-solid interactions. However, the Chinese pharmacopoeia has not recorded this technology. This paper provides an overview of the application and advance of DVS technology in the investigation of pharmaceutical crystal forms and co-crystals, as a reference for related research on polymorphism of drugs.

Orodispersible films are innovative single-layer or multi-layer composite drug-loading films that can be quickly wetted by the patient’s saliva and dissolved in the mouth without the need for drinking water. This review introduces the dosage form characteristics, global development, formulation compositions and process features, research content and general requirements of quality control of orodispersible films. For the quality evaluation of orodispersible films, except for the conventional inspection items of ordinary oral preparations, some special characteristics, such as physical, chemical, and mechanical properties of orodispersible films should also be evaluated based on the dosage form characteristics in order to ensure the safety and effectiveness of the products.

Inherited retinal diseases(IRD) are an important cause of irreversible vision loss or blindness, whose prognosis is poor, and clinically effective intervention methods are lacking. Gene therapy has created new possibilities for IRD treatment. Adeno-associated viral(AAV) is a widely used viral gene therapy vector with application prospects. This paper briefly describes the feasibility of AVV vectors in ocular application, focuses on the preclinical and clinical progress of the application of AAV delivery system for IRD treatment, evaluates the safety and efficacy based on the obtained data, and summarizes the influencing factors of gene therapy for IRD, as well as looks forward to the future research directions, providing references for the technological innovation of IRD treatment and the subsequent product development of AAV vectors.

在我国仿制药一致性评价政策的推动下，随着ICH M9 等指导原则的实施，对参比制剂处方的正确解析直接决定 了是否可豁免仿制药的生物等效试验，且关系到仿制药与参比制剂生物等效试验的成败。该文全方位阐述了如何将逆向 工程法用于参比制剂解析，包括处方、生产工艺及包装等方面，并结合审评经验进行案例分析，旨在引导业界探索更多 的逆向工程技术用于开发高质量的仿制药，以期加速仿制药上市。

Free vitamin K1(VK1) in VK1-loaded mixed micelles(VK1-MM) injection leads to security risks. The encapsulation efficiency is one of the indexes to evaluate the content of free VK1 in mixed micelles and their drug-loading performance, while the applicability of various determination methods is different. This study compared the applicability of extraction, centrifugation, and filtration methods in evaluating the encapsulation efficiency of VK1-MM. The study of the main factor affecting the accuracy of each method showed that the extractant altered the structure of VK1-MM during extraction. In addition, the free VK1 and VK1-MM could not be completely separated by centrifugation, which was related to the tiny density difference between free VK1 and water. However, filtration could effectively separate free VK1 and VK1- MM with the appropriate pore size and material of the filter membrane. The recovery of filtration was 100.40％ (with RSD of 0.80％, n=3), which showed filtration was suitable for determining the encapsulation efficiency of VK1-MM. Simultaneously, the applicability of different encapsulation efficiency determination methods and the characteristics of formulations were analyzed, which provided a reference for establishing a suitable encapsulation efficiency determination method for other micellar preparations.

Chirality is a widely existing property in pharmaceuticals. In general, the chiral enantiomers show higher activity and lower adverse reaction than their racemates. Therefore, the manufacturing of pure chiral enantiomer is of great scientific significance. Crystallization resolution method is an important technique in pharmaceutical industry to achieve the separation of enantiomers. As a novel crystallization technique, cocrystal has attracted much attention due to its broad applicability. In this paper, the history and development of chiral resolution based on cocrystallization are briefly introduced. Meanwhile, the recent progress in this field is classified and summarized according to the structural characteristics of cocrystals formed by racemic drugs. In addition, the main challenges of chiral resolution based on cocrystallization are summarized and prospected.

文章基于药学研究的特点，探讨药学研究不同阶段质量管理的要素，供药学研究机构建立和完善其质量管理体系时参考。 通过对比药学研究与非临床研究、临床试验的异同，以及药学研究与药品生产的异同，分析GLP、GCP 和GMP 对药学研究质 量管理的适用性；通过分析药学研究不同阶段质量管理的特点，探讨药学研究在非GMP、类GMP 和完整GMP 阶段的质量管 理要素。药学研究不同阶段的质量管理目标有所不同，药学研究机构应基于自身工作内容及药学研究各个阶段的质量管理目标 建立相应的质量管理体系，确保药学研究数据的可靠性以及临床试验用药品的质量。

Ozanimod hydrochloride, a new type of oral sphingosine 1-phosphate(S1P) receptor modulator, is clinically used for the treatment of relapsing multiple sclerosis. In this review, the synthetic methods of ozanimod hydrochloride and its key intermediates are summarized and evaluated based on different schemes described in the literature. The scaffold structure of ozanimod hydrochloride is (S)-1-amino-4-(1,2,4-oxadiazol-3-yl)-2,3-dihydro- 1H-indene. Starting from 4-cyano-2,3-dihydro-1H-inden-1-one(2), chiral auxiliary agents or catalysts for asymmetric hydrogenation are used to construct the chiral amino group at the 1-position of 2,3-dihydro-1H-indene. Alternatively, the 1-carbonyl group is converted to the chiral hydroxyl before constructing the chiral amino group. The oxadiazole ring at the 4-position of 2,3-dihydro-1H-indene is synthesized in situ from 4-cyano group.

Tiapride hydrochloride was synthesized from 2-methoxy benzoic acid with an overall yield of 46.0％ by the reaction with chlorosulfonic acid, followed by sodium sulfite and dimethylsulfate to generate methyl 2-methoxy- 5-(methanesulfonyl) benzoate, the latter was reacted with N,N-diethylenediamine, and then by salt formation with hydrochloric acid.

Vaginal drug delivery has attracted great attention due to its advantages such as rich blood supply, large surface area of vagina and avoidance of the hepatic first-pass effect. However, there are still issues such as leakage and discomfort in application of traditional drug dosage forms for vaginal administration. At present, strategies such as bioadhesive materials, thermosensitive materials, pH responsive materials, mucosal penetration techniques and nano technologies have been proposed to improve the retention time, permeability, and release characteristics of drugs in the vagina. Based on the physiological structure and characteristics of the vagina, this review summarizes the delivery strategies and techniques of drug delivery through the vaginal mucosa, hoping to provide a reference for the development of vaginal topical medication and uterine-targeting delivery products.

随着材料科学的发展和制药工业水平的进步，采用可生物降解的聚合物载体材料将化学药物制备为微球注射剂， 可解决药物半衰期短、需频繁给药的问题。但由于微球制备技术较为复杂，实现产业化较困难，目前上市的微球药物制 剂较少。并且，对基于微球的长效注射剂进行仿制也存在较高的技术壁垒，仿制产品数量更是寥寥无几。文章参考化学 药品注射剂仿制药相关技术要求，结合微球注射剂的产品特点和相关文献资料，对其处方工艺开发、质量和稳定性研究 等需要关注的内容进行讨论，以期为化学仿制药微球注射剂的药学研究提供参考。

In recent years, liposome products have been successively launched. However, standardized testing methods for in vitro release of liposomal products have not been incorporated in various pharmacopoeias, which poses great challenges for the development and regulation of liposomal products. In vitro release is an important technical indicator for evaluating the quality of pharmaceutical preparations, and plays an important role in product development, quality research, and product release. This review introduces the in vitro release methods and detection apparatuses of liposomal products reported both domestically and internationally, and elaborates on the selection basis of in vitro release methods suitable for approval products. It is hoped that this review will promote and improve the development of in vitro release methods for liposomes, and provide more scientific and accurate data support for the research and regulation of liposome products.

As a novel drug delivery system, microspheres can provide a sustained-release drug delivery lasting from weeks to months, which reduce drug administration frequency and improve patient compliance. Poly(lactide-coglycolide)( PLGA) has been widely used as a carrier material for microspheres manufacture. However, the molecular characteristics of PLGA are the key influence factors in the stage of formulation design, which are related to the pivotal behaviors of microspheres, such as drug loading, particle size and sustained-release properties. In this paper, by reviewing the recent studies on the preparation and evaluation of PLGA microspheres, five momentous molecular properties of PLGA(such as the relative molecular weight and distribution), which have significant effects on the properties of microspheres are screened out. The effects of each molecular property on the behaviors of microspheres are summarized and the reasons are explained, which provides a reference for the selection of PLGA type in the development of microspheres with expected properties.

The pharmaceutical films are thin sheets formed by various methods such as casting or extrusion, which results in a dispersion of the active pharmaceutical ingredients through the film. They are subject to growing research and have received increasing interests recently due to their convenient administration and improved patient compliance. This review summarizes the marketed products of film dosage form, their quality standards, and storage requirements. Besides, the testing methods of quality inspection items including disintegration time and dissolution are discussed. Finally, brief explanations are provided for the revision of general requirements of pharmaceutical films in the general chapter of the Chinese Pharmacopoeia by comparing with the United States Pharmacopoeia, European Pharmacopoeia, and Japanese Pharmacopoeia.

药品集中采购是降低药价、保障患者用药权益的重要政策，对医药企业生产运作具有指导意义，发展至今已有 20 余年的历史。文章采用文本挖掘法，选取 1999 年 1 月至 2022 年 7 月的国家药品集中采购政策相关文件，分析我国药品 集中采购政策的演变规律，以及其对药品生产企业的阶段性影响，从采购主体、集采规则、配套措施和价值目标 4 个层 面得出结论，并结合现阶段带量采购的实践经验，为集中采购政策的后续开展与医药企业生产规划提出建议。

Soft capsules may encounter a series of stability problems in the processes of production, transportation and storage, such as the adhesion, leakage and delayed disintegration, which greatly shorten the shelflives of soft capsules. High temperature, high humidity, ultraviolet radiation, γ-radiation, rapid drying and other physical conditions or exposing to aldehydes, ketones, imines and other chemical substances will cause cross-linking and aging of soft capsule shell, inducing above stability issues. Developing new types of soft capsule shell material might improve the aforementioned issues. In this review, new soft capsule shell materials are classified according to sources, the research progress of animal-, plant- and microbial-derived materials, as well as modified and synthetic shell materials are introduced, hoping to provide a reference for improving the stability of soft capsules during their shelf-lives.

Oral administration is the preferred method for drug delivery. However, due to the unique properties of drugs and the gastrointestinal barrier, the bioavailability of oral administration is limited. By referencing the structural characteristics of organisms in nature and adopting a biomimetic perspective, the biomimetic nanocarriers can be designed and prepared to improve the oral absorption of drugs, which hold promising development prospects. This review summarizes the application of nanocarriers designed and prepared with various biomimetic ideas in oral drug delivery,offering insights and references for the development and clinical application of oral nanocarriers.

This study used styrene-isoprene-styrene(SIS) block copolymer as the matrix, liquid paraffin as carrier dispersant, hydrogenated petroleum resin as the tackifier, N-methyl pyrrolidone(NMP) as solubilizer, menthol as the penetration enhancer, citric acid as the acidity regulator and butylated hydroxytoluene(BHT) as the antioxidant to prepare loxoprofen sodium(1) transdermal patches. The preparation process was optimized by orthogonal design. The optimized formulation compositons of the patch were as follows: the mass fraction of SIS was 27％, liquid paraffin was 33％, hydrogenated petroleum resin was 26％, citric acid was 1.2％, menthol was 5.67％, and both NMP and BHT were 0.85％. The quality of 1 patch prepared according to the optimal formulation was stable, and the adhesive property was good. Its transdermal effect was equivalent to the reference preparation(the permeability per unit area at 24 h reached 72.69 μg).

To perform the quality control of arbidol hydrochloride, five potential related substances were synthesized. They were ethyl 6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-[(phenylsulfinyl)- methyl]-1H-indole-3-carboxylate(related substance A), ethyl 6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1,2- dimethyl-1H-indole-3-carboxylate(related substance B), ethyl 6-bromo-5-hydroxy-1-methyl-4-[(methylamino)- methyl]-2-[(phenylthio)methyl]-1H-indole-3-carboxylate(related substance C), ethyl 4-[(dimethylamino)methyl]- 5-hydroxy-1-methyl-2-[(phenylthio)methyl]-1H-indole-3-carboxylate(related substance D) and ethyl 6,7-dibromo-4- [(dimethylamino)methyl]-5-hydroxy-1-methyl-2-[(phenylthio)methyl]-1H-indole-3-carboxylate(related substance E). Their chemical structures were confirmed by MS, 1H NMR and 13C NMR.

粉体的性质尤其是流动性对固体制剂的开发和制备具有重要意义。认识和掌握物料的粉体学性质，有助于处方筛 选、工艺改进、质量控制、生产等问题的解决。该文通过分析口服固体制剂研发中粉体学性质研究方面的常见问题，并 结合审评中接触到的实际案例，从审评角度提出了口服固体制剂开发中粉体学指标的控制建议，以期为口服固体制剂的 制剂研究和注册申报提供一定的参考。

ICH《E6(R3) ：药物临床试验质量管理规范(GCP)》是涉及人类参与者的临床试验的国际性伦理和科学质量标准。 遵循GCP 开展临床试验将有助于确保试验参与者的权益、安全和健康得到保护，并且确保临床试验结果可靠。GCP 是各 国药品监管部门对药物临床试验监督管理的重要依据。同时，GCP 是ICH 的一级指导原则，充分实施该原则是认定ICH 成员资格的重要条件之一。文章旨在介绍此次修订的背景、修订进展及修订的亮点，有助于我国各界充分了解E6(R3) 原则及附件1 的修订意涵，为后续遵循和实施E6(R3) 奠定基础。

Dissolving microneedles can deliver drugs directly to subcutaneous lesions with a high drugdelivering capacity by painlessly inserted into the skin. However, due to the limitation of drug loading, their application in clinics has been limited. Therefore, improving the drug loading of microneedles is crucial for the application of dissolving microneedles. This paper reviews three strategies to improve the drug loading of microneedles, namely design of new formulation forms, improvement of microneedle structure and the preparation process of microneedles, hoping to provide a reference for the clinical translational research of microneedles.

Paclitaxel belongs to the diterpenoid compounds and has good antitumor activity against various cancers such as ovarian cancer and breast cancer. Due to its poor solubility, paclitaxel has significant adverse reactions when it was used directly, limiting its clinical application. Serum albumin nanoparticles can compensate for the inherent defects of paclitaxel, enhance the stability of the drug in the body, improve its bioavailability and targeting ability, achieve the purpose of enhancing efficacy and reducing toxicity, and to some extent solve the problem of paclitaxel. This review summarizes the preparation process of serum albumin-paclitaxel nanoparticles, the application of modified serum albumin in paclitaxel-loaded nanoparticles, in order to provide theoretical guidance for the development of serum albumin based nanodrug delivery systems that meet actual clinical applications.

(R)-3-aminobutanol[(R)-1] was a versatile intermediate of several drugs, and it was of great significance to optimize its synthetic process. According to a patent, the final product was (S)-3-aminobutanol instead of the required (R)-product if prepared with (R)-α-phenethylamine[(R)-3] as the chiral auxiliary agent. So, with (S)-3 as the chiral auxiliary agent, compound (R)-3-[[(S)-1-phenylethyl]amino]butan-1-ol[(R)-5] and (S)-5 were prepared by the reductive amination of 4-hydroxy-2-butanone(2), and then (R)-5 and (S)-5 were transformed into the corresponding hydrochlorides. After that, compounds 5 hydrochloride was isolated by recrystallization with a mixed solvent of ethanol and ethyl acetate (volume ratio=3∶1). After alkalization, compound 5 was underwnt the de-benzylation with palladium charcoal and ammonium formate to obtain compound 1 with a total yield of 56.04％(based on 2), a purity of 98.5％ and ee of 99％.

Surface modified liposomes with hyaluronic acid as a new transdermal drug delivery carrier can significantly improve the transdermal penetration of drugs by swelling the stratum corneum through the powerful hydration effect of hyaluronic acid. Due to its unique structure and tumor cell targeting, hyaluronic acid forms a mesh structure on the surface of liposomes, which can realize active targeting, prevent drug leakage, prolong drug release, improve stability, and synergistically enhance antitumor activity. This study mainly introduces the research progress of hyaluronic acid modified liposomes in the aspects of the preparation methods and related parameters, synergistic transdermal absorption of hyaluronic acid and liposomes, enhancement of tumor cell targeting of liposomes, the stability and sustained release effect of modified liposomes, as well as application prospects. It provides a reference for the further development of hyaluronic acid modified liposomes for transdermal drug delivery.

Antibody-drug conjugates(ADC) combine the targeting ability of monoclonal antibodies and the potent cytotoxicity of small molecule substances, becoming a research focus in the current biopharmaceutical field. Although various ADCs have been marketed globally, challenges still exist in formulation and stability. This review outlines the key points and difficulties in ADC formulation development and clinical application from the perspectives of antibody, linker, and small molecule substance selection for ADC, and proposes a stability study plan during ADC use, aiming to provide references for the future ADC development.

This study developed the formulation and preparation of azithromycin(1) dry suspension based on the concept of quality by design(QbD). First, 1 and trisodium phosphate were granulated to improve the taste, then 1 particles and sucrose(grinding) were granulated, followed by mixing with the added sucrose. The second-step granulation and mixing process were optimized by Box-Behnken design with granulation time, adding sucrose ratio after granulation, and mixing time as independent variables and content uniformity as the dependent variable. The optimal process was as follows: granule time was 14 min, adding sucrose ratio was 40％, and mixing time was 44 min. Three batches of process validation samples prepared according to the optimized parameters had an average content uniformity of 2.3. And the dissolution behaviors of self-made preparations(T) and reference preparations(R) were similar in media with pH values of 2.0, 4.5, and 6.0. The bioequivalence between T and R was studied through a three-cycle partially repeated crossover design in healthy volunteers. The results showed that under fasting conditions, the cmax of T and R were 114.675 and 114.917 ng/mL, the AUC0→t were 552.41 and 594.87 h·ng·mL–1; under fed conditons, the cmax of T and R were 37.755 and 32.945 ng/mL, the AUC0→t were 276.66 and 257.87 h·ng·mL–1. The statistical analysis results of reference-scaled average bioequivalence(RSABE) or average bioequivalence(ABE) showed that T and R were bioequivalent. The quality and efficacy of the 1 dry suspension prepared in this study were consistent with the reference.

The rapid development of inhaled products, especially dry powder for inhalation, highlights the quantitative demands for the amorphous content of micronized bulk drugs. This review briefly describes seven widely used quantitative methods, named PXRD, DSC, dynamic vapor adsorption, microcalorimetry, solution calorimetry, IR and Raman spectroscopy methods, as well as their limitations and corresponding detection instruments. And based on the common limit requirements of amorphous content for inhaled bulk drugs, some examples are provided. The advantages and disadvantages of different methods are analyzed to provide some references for related researches.

Carbonyl reductases(CREDs) are valuable tools in the synthesis of chiral drugs. In this study, 96 CREDs from different sources were obtained by gene mining strategy, then cloned and expressed in Escherichia coli to construct CRED library 1.0. The catalytic performance of the enzyme library for eight substrates with different structures was investigated. The results showed that the catalytic performance of CREDs on various substrates with distinct structure was significantly different. Several enzymes with high catalytic activity were screened out from the enzyme library, such as K21, K42, K38 and K73, which can efficiently catalyze ethyl acetoacetate, 4-chloroacetoacetate ethyl ester, acetophenone and ethyl benzoylacetate, respectively. Later, the process development for the efficient preparation of optically chiral alcohol (S)-4-chloro-3-hydroxybutyrate(ee>99％) by carbonyl reductase K42 and K87, the synthesis of (R)-4-chloro-3-hydroxybutyrate(ee>99％) by K94 were successfully realized with a space-time yield of 800 g·(L·d)–1. The carbonyl reductase library 1.0 provided a new tool box for industrial synthesis of chiral drugs.

Tumor is closely related to the copper disorder in human body. In order to discover new copper ion chelating antitumor compounds, five 8-hydroxyquinoline derivatives were synthesized by C-2 aldol condensation, elimination and Michael reaction with 2-methyl-8-hydroxyquinoline as the starting material. The copper ion chelating ability and selectivity were studied by ultraviolet titration. And their cytotoxicity against human melanoma cells(A375 cells and Colo829 cells), human lung cancer cells(A549 cells), human liver cancer cells(HepG2 cells), human cervical cancer cells(HeLa cells) and human immortalized keratinocytes(HaCaT cells) was determined by MTT assay. Finally, two compounds TDMQ51 and TDMQ53 showed higher safety than the positive control fluorouracil(5-FU), while the complexation constants for copper and zinc differed by 13 orders of magnitude. These two compounds could be studied intensively as lead compounds owing to the good inhibitory activity to a wide variety of tumor cells.

我国药品基本医疗保险目录已形成了“独家品种谈判准入、非独家品种竞价准入”的分类准入机制，有效增加了 临床用药的选择。但目前医保准入路径适用分类仅以批文数量作为唯一划分标准，导致有核心专利权的多批文药品丧失 谈判资格，只能通过竞价准入路径进入国家医保药品目录，其在医保准入中的启动决定权、价格决定权和“双通道”推 荐权被削弱。文章建议完善医保准入流程，采取“批文+专利”的分类处理模式，从而更好地保护创新药专利权，为我国 药品基本医疗保险目录的准入提供更为公平、合理的环境。

文章在对药品生产洁净环境监测相关法规进行分析的基础上，结合药品生产企业洁净环境监测实践，将药品生产 洁净环境监测注意点划分为监测程序规定、监测计划和监测实施3 个方面，进行要点及注意事项的分析与阐述。并通过 国内外药品检查时在药品生产洁净环境方面发现的缺陷进行统计分析，对缺陷分布情况及典型问题进行介绍，为我国药 品生产企业，特别是无菌药品生产企业，进一步做好药品生产洁净环境监测提供参考与借鉴，同时也为各类药品生产洁 净环境监测的检查提供思路。

Amorphous solid dispersion is one of the most effective formulation approaches to enhance the oral bioavailability of poorly water-soluble drugs with wide application prospects. However, due to the “aging”, a solid state physical stability problem, which affects the dissolution in vitro and absorption in vivo, the development of amorphous solid dispersion-based preparations faces great challenges. The solid state physical stability is affected by many factors such as formulation composition, preparation process and storage conditions. In this paper, formulation composition, preparation process and quality control of amorphous solid dispersion-based preparations are summarized in order to provide the guidance for the development of amorphous solid dispersion-based preparations.

药品上市后的变更分为审批类变更、备案类变更和报告类变更，化学药品中等变更属于备案类变更。该文对福建 省药品监督管理局2021 年1 月至2023 年3 月受理的158 个化学药品中等变更备案资料，进行回顾性分析，并结合审评 经验、沟通交流案例梳理出典型问题，为加强药品上市后的变更管理提出了建议。这将有助于企业完整、准确地理解相 关要求，高效进行化学药品变更的研究/ 验证工作，同时也为药品监管部门开展化学药品中等变更备案审查提供了较详 实的技术参考。

除菌过滤系统及无菌生产工艺是保证非最终灭菌药品无菌性的重要环节。对除菌过滤系统进行使用前灭菌后完整 性测试(pre-use post sterilization integrity test，PUPSIT) 可确保其能有效拦截所有微生物。该研究梳理了国内外药品监管 机构对PUPSIT 及其节点的法规要求，分析、探讨了PUPSIT 的实施利弊和行业现状，以期为药品监管机构和无菌药品生 产企业提供参考。

Astaxanthin, as a fat-soluble carotenoid, has strong antioxidant properties. However, its application is limited due to the poor water solubility, extreme sensitivity to temperature, light and oxygen, and low bioavailability. Nowadays, new nano drug delivery systems have advantages in improving the aforementioned defects. In this paper, the current research status and application of astaxanthin nano preparations based on lipid, polysaccharide and protein are reviewed. Then, the directions of research on astaxanthin nano delivery systems are generalized and contemplated, hoping to provide references for the future clinical application of astaxanthin.