Process analysis technology(PAT)is of great significance to improve the process control and quality as-surance in the manufacture of dermal drug delivery products.This paper reviewed the application of PAT technology in the advanced manufacturing of dermal drug delivery products,introduced the basic situation of PAT and chemo-metrics,and summarized the commonly used PAT tools and their application examples in recent years.In the fu-ture,PAT will play a greater role in the process ofdermal drug delivery products,but the research in this area is still very scarce now.

This paper combed the principle and characteristics of microdialysis(microperfusion)technology,sum-marized the application status in transdermal drug delivery system and analyzed the problems and challenges.It also outlooked on future development direction and provide relevant suggestions which can contribute to provide refer-ence for further research in this field.

As non-invasive drug delivery systems,transdermal patches can deliver drugs through the intact skin at a fixed dose and a adjustable rate in order to product a systemic or local therapeutic effect.Focused on the key quality attributes of transdermal patches,the article illustrated the testing methods and how to control key points.It also briefly described the testing methods and standards of some other characteristics referring to pharmacopoeia,current policies and regulations in various countries,which provided a reference for pharmaceutical industries and relevant departments to improve the quality control methods and standards.

Objective:Different methods were used to determine the dissolution of piroxicam patch,and the disso-lution results were evaluated,in order to select a determination method that could more accurately reflect the drug release process of piroxicam patch,so as to provide a reference for the scientific and accurate evaluation of drug quality.Methods:The liquid chromatography method for the detection of piroxicam was established,and the 24 hour dissolution curves of piroxicam patch were investigated by paddle over disk method,rotating cylinder method and vertical diffusion cell method,and the dissolution curves were compared by f1 difference factor method,f2 simi-larity factor method and Weibull model fitting,and the in vitro dissolution behavior of different methods was evalua-ted.Results:Piroxicam had a good linear relationship in the range of 1-150 μg·mL-1(r=1.000),the accura-cy was 100.9％(n=9),the precision was 1.7％(n=9),and the sample solution was stable within 72 hours.The results of the comparison of dissolution curves showed that the dissolution of piroxicam patch was more in line with the Weibull model.Under the same conditions of dissolution medium and temperature,there was little differ-ence between the paddle over disk method and rotating cylinder method,and there was a possibility of substitution for each other,and there were significant differences between the vertical diffusion cell method and the other two methods.Conclusion:The vertical diffusion cell method is more in line with the dissolution process of drugs in actual use,and provides more references for quality evaluation.

Objective:To establish the qualitative and quantitative methods of Lomatogonium carinthiacum(Wulf.)Reichb.in the prescription of Mongolian medicine Polypill Zhuanglun-5 decoction,and solve the phe-nomenon of Lomatogonium carinthiacum(Wulf.)Reichb.being replaced.Methods:Microscopic identification method was used to observe the pollen grains in the powder;The reference substance of swertiamarin and Lomato-gonium carinthiacum(Wulf.)Reichb.were used as the control,and the ethyl acetate methanol water formic acid(12∶2∶2∶0.5)was used as the developing agent for TLC identification;HPLC was used under the condin-tion including Agilent Eclipse Plus C18(250 mm × 4.6 mm,5 μm)as chromatographic column and 0.2％phosphoric acid solution(A)-acetonitrile(B)as mobile phase with gradient elution at 238 nm of detection wavelength were used.Contents of Zhuanglun-5 decoction from different manufacturers were determined with swertiamarin as reference substance.Results:Among the 12 batches of Zhuanglun-5 decoction,8 batches were Lomatogonium carinthiacum(Wulf.)Reichb.,2 batches were Viola yedoensis,and 2 batches were other medicinal materials.The content of swertiamarin in 8 batches of Zhuanglun-5 decoction ranged from 0.2 to 11.7 mg·g-1.Conclusion:The established identification method is simple and effective,and the content determination method is stable and has strong specificity.It can provide technical support for the supervision of the preparation,and has a reference effect for the improvement of traditional Chinese and Mongolian pharmaceuti-cal preparation standards.

Objective:To determine the relative correction factor of pre-vitamin D and simplify the calculation method of vitamin D assay.Methods:By studying the calculation method of vitamin D content in drug standards of various countries,HPLC was used to determine the relative correction factor of pre-vitamin D,and the influencing factors of determination were investigated.Results:The relative correction factors of pre-vitamin D at 254 nm and 265nm wavelength were determined by statistical analysis of 7 laboratories in China.Conclusion:Using the pre-vi-tamin D relative correction factor method to calculate the total amount of vitamin D simplified the experimental steps can be simplified by the pre-vitamin D relative correction factor method to calculate the total amount of vitamin D and the random operating errors can be avoided.The method is rapid and accurate,and lay a solid foundation for further improving the standard of vitamin D preparations.

Objective:To optimize the detection method for residual solvents of esmolol hydrochloride for control of internal quality.Methods:Gas chromatography headspace injection method was adopted by selecting appropriate headspace equilibrium temperature and time in order to reduce sample contamination of the instrument,optimizing solvent ratio for reducing matrix effect and adjusting carrier gas flow rate and split ratio.Polar capillary column pro-grammed temperature rise method was used with high temperature holding time,etc.,and methodological validation was conducted.Results:Ether,ethyl acetate,methanol,and toluene could all be effectively separated with good precision,and there were good linear relationships between peak areas and mass concentrations.The accuracy of sample spiking at 50％,100％,and 150％concentrations was investigated,and the average recovery rates could all reach ranges of 94.8％-105.6％.Conclusion:This method is accurate,highly sensitive,and overcomes the shortcomings of the Chinese Pharmacopoeia methods.It can be used for the detection of residual solvents in esmolol hydrochloride.

Objective:To establish a method of inductively coupled plasma mass spectrometry(ICP-MS)for the simultaneous determination of 24 elemental impurities in dizocine injection in accordance with the relevant regula-tions of ICH Q3D.Methods:ICP-MS method was adopted to analyze the sample solutions after being diluted and then corrected by spiking indium and bismuth as internal standards,the plasma output power was set at 1 550 W,the sampling depth was set at 5 mm,the maximum load volume was set at 1.038 L·min-1,the cooling gas was set at 14 L·min-1,the auxiliary gas was 0.8 L·min-1,the peristaltic pump speed was 40 r·min-1,the injection system was hydrofluoric acid resistant system,the sampling cone and the pattern of the intercept cone were nickel cone and the sampling mode was manual and repeated 3 times.Results:All 24 elements were linear(all r were more than 0.99),the average recoveries were between 80.46％and 102.95％,the repeatability were less than 10.88％,and the intermediate precision were not more than 6.49％.The results of 24 elemental impurities in 3 different batches of dizocine injection met requirements of ICH Q3D.Conclusion:The ICP-MS method is conven-ient,rapid,sensitive and accurate,and can be used to detect the concentrations of 24 metal elements in dizocine injection,which may provide a basis for more strict quality management of the injection.

Objective:To establish an HPLC-DAD wavelength-switching method for the determination of aspirin dipyridamole tablets and free salicylic acid.Methods:An Agilent ZORBAX SB C18 column(250 mm ×4.6 mm,5 μm)was adopted with acetonitrile-tetrahydrofuran-glacial acetic acid-water(20∶5∶5∶70)as the mobile phase,and isocratic elution was performed at the flow rate of 1.0 mL·min-1,the column temperature of 30 ℃,and the detection wavelengths were 276 nm for aspirin,284 nm for dipyridamole and 303 nm for salicylic acid.Results:Aspirin,dipyridamole and free salicylic acid had a good linear relationship in the range of 38.37-383.71,9.60-96.05 and 1.02-10.21 μg·mL-1 respectively.The average recoveries were 99.88％(RSD=0.23％),99.01％(RSD=0.46％)and 100.99％(RSD=0.75％),respectively.There was no signif-icant difference for the content resuls between the established method and the standard method.The content uni-formity of A+2.2S ranges from 4.7 to 6.4.Conclusion:The established method is simple and suitable for the quality control of aspirin dipyridamole tablets.

The first supplement of the Pharmacopoeia of the People's Republic of China 2020 Edition will be imple-mented on March 12,2024.It plays an important role in connecting link between the preceding and the following.Among them,11 new pharmaceutical excipients monographs have been added and 46 monographs have been revised.This formulation and revision of pharmaceutical excipients standards are based on the concept of risk man-agement and the full lifecycle management and focuse on ensuring the clinical safety and effectiveness of drugs,the evaluation of critical quality attributes on pharmaceutical excipients is highlighted in the standard-making process,and functional-related characteristics(FRCs)and safety indicators are included.Moreover,the excipient standards have emphasized the concept of international pharmacopeia harmonization and green environmental protection and strengthened the standardization and operability.This article focuses on the general framework and the main charac-teristics of the standards of pharmaceutical excipients in the first supplement of the Chinese Pharmacopoeia 2020,which can contribute to accurately understand and utilize the standards in the Chinese Pharmacopoeia.