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.

Compared with traditional topical formulations, foam agents have many advantages, including easy application, less residue, high penetration, which are suitable for local administration to the skin or mucosa. Therefore, this dosage form has good patient compliance. Establishment of simple and reproducible evaluation method is particularly important for the development of foam agents. In addition, the researches on non-propellant, nanocarrier-based and bionic foam agents further expand the advantages of foam agents, and the application of new manufacturing technique accelerates the industrialization of foam agents. In this paper, the performance evaluations for the expansion, stability, density, rheology and permeability of foam agents, the recent research progress and manufacturing technique of foam agents are reviewed to provide some references for the development of green and efficient foam agents.

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.

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.

Inhalation therapy is the superior choice for treating respiratory diseases. Unlike traditional methods of drug administration, inhalation therapy requires the use of inhalation devices to deliver the drugs to targeted areas. Innovations in inhalation devices aim to improve the delivery efficiency, reduce the impact of respiratory flow rate on drug delivery and improve patient compliance. This paper reviews the development trends of oral inhalation devices and their progress in intelligentization. The soft mist inhaler based on innovative microfluidic nebulization technology and its nebulization mechanism and delivery characteristics are analyzed and discussed. Moreover, this paper further elaborates on the different stages of the development of intelligent inhalation devices. The impact of intelligent inhalation devices on patient compliance is also discussed, providing a reference for further research on intelligent inhalation devices.

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.

2-Phenylcyclopropylamine and its derivatives are important chiral pharmaceutical intermediates for antineoplastics, antidepressants and anticoagulants. The strategies for the synthesis of 2-phenylcyclopropylamine mainly include direct synthesis from cyclopropane-based derivatives and de novo construction of cyclopropane(Corey- Chaykovsky reaction, Kulinkovich-de Meijere reaction, etc.). In this paper, synthetic routes of 2-phenylcyclopropylamine derivatives are systematically summarized and outlined, the advantages and disadvantages of each route are briefly reviewed.

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.

In recent years, pulmonary infectious diseases have posed a serious threat to human health. Compared with the traditional oral and injection administration routes, inhalation administration is increasingly used to treat pulmonary infectious diseases. This route can achieve targeted delivery of drugs to the infected sites, and has the advantages of improving the pulmonary bioavailability, reducing systemic adverse reactions and drug resistance, and therefore has gained widely concern. This paper summarizes the research progress of inhalation preparations for treatment of pulmonary infectious diseases, with a view to providing references for the research and development of anti-infective drugs for pulmonary inhalation.

药品上市许可持有人在委托生产时，可能会面临技术转移中知识产权保护的挑战。文章聚焦于实际中的药品技术 转移，梳理了药品技术转移过程中可能存在的知识产权相关问题，如生产工艺信息的泄露、过度保密导致的技术转移不 充分、技术创新的产权归属纠纷等，并从提升知识产权保护意识、完善技术转移合同、落实项目责任管理制等方面提出 了相应的解决对策，以期帮助持有人和受托方长期合作，实现双赢的目标。

Raman spectroscopy and imaging technology were applied to investigate percutaneous penetration profiles of drugs in this paper. Raman spectra of the ex vivo skin samples were collected by mapping technique. Then, a semiquantitative analysis model of concentration and signal intensity of an analyte had been established using multiple linear regression. On this basis, the contribution coefficients of concentration were presented in the form of heat maps to achieve the visual analysis of permeability distribution of the analyte in the skin. Percutaneous permeation analysis of salicylic acid in pig skins was conducted using Raman spectroscopy and imaging technology. The concentration contribution coefficients of salicylic acid were 0.231％ and 0.275％ in the stratum corneum, and 3.1×10–4 and 2.4×10–4 in the active epidermal layer in the parallel experiments. Compared with the results determined by HPLC method, it was found that the change trend of drug concentration by the two methods was consistent, indicating that the concentration contribution coefficient obtained by Raman spectroscopy could be used for semiquantitative analysis, which provided a new technical means for studying the percutaneous absorption characteristics of the analyte and formulation optimization. In addition, the permeation distribution of hyaluronic acid with different relative molecular weights in pig skin was also investigated by this method, and the visual analysis of distribution of macromolecular drugs in skin was also realized.

偏差管理是药品生产质量管理规范体系中的重要组成部分。文章结合文献研究和工作实践，分析目前制药企业偏差 管理的现状及存在问题，与某制药企业偏差管理存在问题基本一致。继而针对某制药企业建立了一套完整的偏差管理系 统，通过偏差调查深入挖掘偏差产生的根本原因并采取合理的纠正预防措施，以有效降低偏差事件的发生，提高某制药企 业的质量管理水平，切实保证药品质量、维护患者用药安全，期望能为国内制药企业改进偏差管理提供良好的借鉴。

警告信是FDA 对被检查企业或个人存在违规行为而采取的监管措施。该文对2018 至2021 年FDA 发给中国药品 生产企业的药品cGMP 警告信缺陷项目进行统计，并与国内文献研究中我国药品GMP 检查缺陷情况进行对比，分析我 国药品生产企业普遍存在的缺陷以及FDA 和我国药品监管机构在药品GMP 检查重点方面的区别，为我国药品生产企业 改进缺陷项目和通过药品GMP 检查提供建议。

An HPLC-CAD method was established for the determination of seven related substances(2 - 8) in sugammadex sodium(1) bulk drug. The Poroshell 120 SB-C8 column(4.6 mm×150 mm, 2.7 μm) was used, and the analysis was carried out in the linear gradient elution mode with 0.5％ formic acid solution as mobile phase A, and methanol as mobile phase B. The flow rate was 0.5 mL/min and the column temperature was 35 ℃. The temperature of the atomizer of the charged aerosol detector(CAD) was 35 ℃, the filtration constant was 3.6 s, and the data acquisition rate was 5 Hz. The results showed that it was linear for 3 in the range of 5 - 300 μg/mL, and it was linear for 1 bulk drug and other related substances in the range of 2 - 40 μg/mL. The LOQs and LODs of 1 - 8 were 0.985 - 1.145 μg/mL and 0.493 - 0.573 μg/mL, respectively. The average recoveries(n=9) of 2 - 8 were 95.6％ - 99.4％, with the RSDs of 1.21％ - 3.32％. This method is accurate, reproducible, and highly precise, which can be used to detect the related substances in 1 bulk drug, and also provides a reliable detection method for the quality control of 1.

A novel synthetic process of riluzole(1) was reported in this paper. 1-[2-Mercapto-4- (trifluoromethoxy)phenyl]thiourea(4) was prepared through the condensation of 2-amino-5-(trifluoromethoxy) benzenethiol(2) and thiourea(3) in the presence of hydrochloric acid. Then, 4 was transformed into the target compound through intramolecular cyclization catalyzed by CuSO4·5H2O/TEA system with an overall yield of 79.3％(based on 2) and a purity of 99.9％. This synthetic method with stable process and simple operation has not yet been reported in previous literature.

An improved synthetic process of roxadustat(1) was reported. Methyl 4-hydroxy-7- phenoxyisoquinoline-3-carboxylate(2) was chlorinated by 1,3-dichloro-5,5-dimethylhydantoin to obtain methyl 1-chloro- 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate(3), 3 was transformed into 1-methyl-4-hydroxy-7-phenoxyisoquinoline- 3-carboxylic acid(4) through coupling reaction with methylboronic acid and hydrolysis. Then 4 was amidated with glycine methyl ester hydrochloride to generate methyl (1-methyl-4-hydroxy-7-phenoxyisoquinoline-3-carbonyl)- glycinate(5). Finally, the target compound 1 was obtained from 5 by hydrolysis reaction with a purity of 99.9％ and an overall yield of 60.8％(based on 2). The optimized process was easy to operate and had been verified by pilot test, which was suitable for industrial production.

包衣微丸制剂具有掩盖药物的不良臭味、改善药物含量均匀性、提高药物稳定性与改变药物释放特性等特点，是 当前仿制药研发及申报的热点。文章介绍了包衣微丸的结构、制剂的处方组成以及包衣工艺的特点。结合生产现场检查 中的常见问题，对仿制药申报中包衣微丸制剂的处方工艺及质量研究进行了分析和探讨。

In this study, the synthetic method of the small molecule antineoplastics alpelisib(BYL719, 1) was improved. Using 2,4-dibromopyridine as the starting material, the key intermediate 4-bromo-2-(1,1,1-trifluoro- 2-methylpropan-2-yl)pyridine(8) was obtained via 5 steps, including nucleophilic substitution, silylation protection, deprotection, methanesulfonylation and substitution. Intermediate 8 condensed with [2-[(tert-butoxycarbonyl)amino]-4- methylthiazol-5-yl]boronic acid under the Pd-catalyzed Suzuki coupling reaction to give [4-methyl-5-[2-(1,1,1-trifluoro- 2-methylpropan-2-yl)pyridin-4-yl]-tert-butyl thiazol-2-yl]carbamate. Followed by removing the Boc protection group and condensation, the target compound 1 was obtained in a 15.9％ total yield.

Ionic liquids is a low-temperature subclass of molten salts formed by organic cations and organic or inorganic anions, and its melting point is generally less than 100 ℃. Due to the designability of its anion and cation structures and the emergence of biocompatible anions and cations, toxicity of ionic liquids has been reduced, and related researches on drug delivery based on ionic liquids are increased. This review briefly introduces the development and design principles of ionic liquids, and summarizes the roles of ionic liquids in transdermal drug delivery systems, such as increasing the solubility of poorly soluble drugs, changing the permeability of biofilms, acting as drug delivery carriers and forming active pharmaceutical ingredient-ionic liquids(API-ILs). Finally, the safety and clinical application of ionic liquids are summarized, and the future development is prospected.

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.

Continuous flow process for the synthesis of losartan(1) was realized by microchannel reactor technology based on the synthetic routes reported in the literature. Compound 1 was obtained with an overall yield of 70.3％ [based on 2-cyano-4'-methylbiphenyl(2)] via bromination, N-alkylation and tetrazolium cycloaddition reaction using 2 and 2-butyl-4-chloro-1H-imidazole-5-carboxaldehyde(3) as the starting materials. The optimized process bearing mild reaction conditions, simple operation and higher security is suitable for industrial production．

Bromhexine hydrochloride(1) is a commonly used expectorant, showing a polycrystalline phenomenon. Crystal transformation might affect its efficacy. Infrared spectroscopy(IR), powder X-ray diffraction(PXRD), and differential scanning calorimetry(DSC) analyses were adopted to characterize crystal patterns of 1 in its granules and dispersible tablets, and the crystal stability of 1 during the preparation and storage processes was studied. Through IR and PXRD analyses, three different crystal forms of 1 could be identified, while the characterization results of three different crystal forms by DSC were not remarkable. The results indicated that crystal form A of 1 showed good crystal stability and did not undergo crystal transformation during the preparation processes of granules and dispersible tablets or storage under high temperature, light, and high humidity conditions. This paper provided data for improving quality control levels and monitoring the production process.

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。

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.

Vagina has the advantages of rich blood supply, large surface area and avoidance of liver first-pass effect, which is beneficial for the drug to exert its pharmacological effect. Among vaginal drug delivery systems, semisolid formulations have a certain fluidity and a larger spreading area in the vagina compared with solid formulations, which increases the absorption of drugs by the vaginal mucosa. The temperature-responsive gel for vaginal use can respond to the change of temperature and transform to a semi-solid from a liquid, so it is easy to spread and resist the clearance effect of vaginal fluid. This paper reviews the quality characterization and in vitro evaluation methods of semisolid preparations for vaginal use through literature search, hoping to provide some references for the further development of semi-solid preparations.

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.

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。

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.

Pullulan(1), a natural polymer, has been increasingly widely used in the pharmaceutical and food industries because of its solubility, malleability, spinnability, edibility, biodegradability, non-toxicity, and well biocompatibility. It can be used as the film-forming material to prepare films, as the capsule shell material to prepare capsules, as the biodegradable material to prepare microneedles and injections, and as the carrier material for targeted drug delivery. This paper introduces the characteristics of 1, briefly reviews its current status in application in pharmaceutical preparations, and offers a prospect of 1 development.

Owing to simple preparation process, high drug loading capacity and strong adhesion, nanocrystals can effectively solve the problems of short-term retention time, slow release rate and low bioavailability of poorly watersoluble drugs. Therefore, it has become a hot research topic in pharmaceutics in recent years. In this paper, the preparation technologies of nanocrystals and their research progress of applications in mucosal drug delivery systems such as nasal, ocular, oral, skin and pulmonary delivery systems are reviewed, hoping to provide a reference basis for the development of nanocrystal-based dosage forms of poorly soluble drugs.

药物晶型是影响药物疗效的重要因素，关系到药物的安全性、有效性和质量可控性。近年来，药物晶型研究已成 为国内外研究的热点。该研究结合国内外药品监管机构的指导原则、技术要求以及当前国内审评技术要求，分析药物晶 型研究的关注点、表征方法及典型案例，旨在为多晶型药物的开发和仿制药注册申报提供参考。

Posterior segment diseases are the leading causes of visual impairment and blindness, and their treatments are mainly based on invasive approaches with many complications, serious adverse reactions and poor patient compliance. Non-invasive ocular drug delivery systems should be developed to overcome the ocular absorption barriers, increase drug permeability into posterior segment, so as to improve the drug bioavailability in posterior segment. This paper overviews the ocular barriers and novel non-invasive strategies(including the use of penetration enhancers, nanotechnology and iontophoresis) of drug delivery to the posterior eye segment. Moreover, the challenges of translational medicine and candidate drugs under clinical trial are summarized. Finally, the prospects of non-invasive posterior segment delivery are put forward.

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.

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.

Firstly, the formulation and process of curcumin nanoemulsion were optimized by single factor test and Box-Behnken design combined with response surface methodology with encapsulation efficiency as evaluation index, and the physicochemical properties of curcumin nanoemulsion prepared under the optimal conditions were investigated. The results showed that the encapsulation efficiency of curcumin nanoemulsion was (95.69±0.04)％, and the particle size was (109.7±0.5)nm. Transmission electron microscopy showed that curcumin nanoemulsion was homogeneous spherical. Then the optimal curcumin nanoemulsion was added to the composite matrix gel composed of poloxamer 188 and poloxamer 407 to prepare a transdermal thermosensitive hydrogel, and its quality was evaluated and its transdermal performance was studied. The results showed that the hydrogel had good temperature sensitivity, the gelation temperature and time were (34.3±0.3)℃ and (54.2±10.2)s, respectively. The cumulative penetration amount Q24 h of the hydrogel was (9.93±0.70)μg/cm2 and the steady transdermal rate Js was 0.71 μg·cm–2·h–1, which were 2.5 times and 2.6 times of those of the curcumin solution, respectively. Finally, 2,4-dinitrochlorobenzene was used to establish a mouse model of chronic eczema, and the efficacy of the title product was investigated with the commercial compound dexamethasone acetate cream as a positive control. The results showed that compared with the model group, the title product could significantly reduce the ear mass difference and swelling degree of mice(P<0.05), and there was no significant difference in efficacy between the positive control(compound dexamethasone acetate cream) group and the product(P>0.05). In addition, the efficacy of this product was significantly different from that of the curcumin solution(P<0.05).

Drug-device combination products have become a hot spot of innovation with the rapid development of modern science and technology. Drug-device combined products integrate the functions of medicines and medical devices, so they generally have the characteristics of high risk and complex technical performance. The development of drug-device combination products in China is still in its infancy and the regulatory system needs to be gradually improved. The guidances issued by U.S. FDA describe the key role of human factors engineering in the development of drug-device combination products, as well as the importance of human factors engineering to product safety and effectiveness. The relatively mature review thinkings of U.S. FDA might have a positive role in promoting the understanding of human factors engineering and evaluation of some related indicators for drug-device combination products of regulatory authorities in China.

To improve the quality of sodium valproate, a commonly used anti-epileptic drug, its related substance 2-isopropyl pentanoic acid(1) was synthesized. The compound methyl 2-cyano-valerate(3) was obtained by the reaction of methyl cyanoacetate(2) and bromopropane in methanol solution of sodium methoxide. And then, 3 was reacted with 2-iodopropane in methanol solution of sodium methoxide to synthesize methyl 2-cyano-2-isopropyl valenate(5). Followed by hydrolysis and decarboxylation, hydrolysis with sodium hydroxide and acidification with sulfuric acid, the title compound 1 was obtained with a total yield of 4％ and the purity of 98％.

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。

Baicalein, a flavone derived from Scutellaria baicalensis, exhibits antitumor effect by suppressing tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor angiogenesis, and regulating the tumor microenvironment. However, its poor solubility has attenuated the bioavailability and thus restricting the efficacy. Many studies utilize nano-drug delivery systems to improve bioavailability and antitumor efficacy of baicalein. This review summarizes the recent studies concerning the antitumor mechanisms of baicalein and its nano delivery systems to provide approaches for its further basic research and clinical application.