COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest tha...COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest that cytokine storms(interleukins)may play an important role in severe cases of COVID-19.Neutralizing key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality rate.Tocilizumab(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS patients.Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical trials.This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug shortages.Here,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of TCZ.It is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.展开更多
Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the mul...Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments.The application of mesenchymal stem/stromal cells(MSCs)as therapeutic drugs has provided novel treatment options for diverse degenerative and chronic diseases including KOA.However,the complexity and specificity of the“live”cells have posed challenges for MSC-based drug development and the concomitant scale-up preparation from laboratory to industrialization.For instance,despite the considerable progress in ex vivo cell culture technology for fulfilling the robust development of drug conversion and clinical trials,yet significant challenges remain in obtaining regulatory approvals.Thus,there’s an urgent need for the research and development of MSC drugs for KOA.In this review,we provide alternative solution strategies for the preparation of MSC drugs on the basis of the principle of quality by design,including designing the cell production processes,quality control,and clinical applications.In detail,we mainly focus on the quality by design method for MSC manufacturing in standard cell-culturing factories for the treatment of KOA by using the Quality Target Product Profile as a starting point to determine potential critical quality attributes and to establish relationships between critical material attributes and critical process parameters.Collectively,this review aims to meet product performance and robust process design,and should help to reduce the gap between compliant products and the production of compliant good manufacturing practice.展开更多
In recent years,new preparations of traditional Chinese medicines(TCMs)have been developed,increasing the need for their clinical trials.Using placeboes rather than control drugs is increasingly popular in clinical tr...In recent years,new preparations of traditional Chinese medicines(TCMs)have been developed,increasing the need for their clinical trials.Using placeboes rather than control drugs is increasingly popular in clinical trials of TCMs,as the therapeutic effects of the tested TCMs can be more properly judged.The basic attributes of TCM placeboes include similarity,safety,applicability and controllability.In particular,it is necessary to have similarities in appearance,color,smell and taste between the tested TCMs and placeboes.This is quite difficult for some TCMs due to their distinctive smell and taste.On the other hand,according to the TCM theory on homology of medicine and food,many foods also have certain bioactivities,potentially further complicating the selection of materials for TCM placeboes.In this review,firstly,studies on the special smell and taste of TCMs were introduced.Then,the preparation quality evaluation processes for TCM placeboes were summarized and discussed,based on the relevant literature published in recent years and the research results from our own lab.This review will facilitate the further research and development of TCM placeboes.展开更多
Objective This study aimed to design and optimize the water extraction process for Chuantieling(喘贴灵,CTL)based on the concept of quality by design(QbD).Methods The single-factor experiments were used to select the b...Objective This study aimed to design and optimize the water extraction process for Chuantieling(喘贴灵,CTL)based on the concept of quality by design(QbD).Methods The single-factor experiments were used to select the best experimental points of CTL water extraction.On this basis,the transfer rate of ephedrine hydrochloride and sin-apine thiocyanate,and the yield of the extract were evaluated as the evaluation indicators.The liquid-solid ratio,extraction time,and pH value were selected as the main factors to carry out the Box-Behnken design(BBD).A mathematical model of the critical process parameters(CPPs)and critical quality attributes(CQAs)was established,the interaction between CQAs and CPPs was examined,and the CTL extraction process design space was established and optimized,which guaranteed the stability of the process.The high performance liquid chro-matography(HPLC)was used to analyze the main active compounds in the CTL extract.Results Through single-factor experiments,the best experimental parameters were found to be a liquid-solid ratio of 8∶1,extraction time of 90 min,pH value of 4,and extraction times of three.The experimental variance analysis results of the BBD showed that the P value of the re-gression model was less than 0.05,and the lack-of-fit value was greater than 0.01,indicating that the constructed model had good predictive ability.The operating space of the CPPs of the CTL water extraction process was combined with the actual production situation.In the pro-duction situation,the best extraction process was nine times of water addition,72 min of ex-traction time,and 4.5 of pH value.The HPLC results showed that the peak areas of ephedrine hydrochloride,sinapine thiocyanate,tetrahydropalmatine,methyl eugenol,cinnamaldehyde,and 6-gingerol in the CTL extract accounted for 0.94%,14.32%,0.78%,31.23%,0.34%,and 0.44%of the total peak area,respectively.Conclusion The water extraction process design space of CTL based on QbD was conducive to actual production operations,ensuring the stability of the process.展开更多
The microstructures of pharmaceutical preparations play a pivotal role in determining their critical quality attributes(CQAs),such as drug release,content uniformity,and stability,which greatly impact the safety and e...The microstructures of pharmaceutical preparations play a pivotal role in determining their critical quality attributes(CQAs),such as drug release,content uniformity,and stability,which greatly impact the safety and efficacy of drugs.Unlike the inherent molecular structures of active pharmaceutical ingredients(APIs)and excipients,the microstructures of pharmaceutical preparations are developed during the formulation process,presenting unique analytical challenges.In this review,we primarily focus on presenting the research methods used to elucidate the microstructures of pharmaceutical preparations,including X-ray imaging(XRI),scanning electron microscopy(SEM),atomic force microscopy(AFM),Raman spectroscopy,infrared(IR)spectroscopy,and rheometer technology.Subsequently,we highlight the applications,advantages,and limitations of these methods.Finally,we discuss the current challenges and future perspectives in this field.This review aims to provide a comprehensive reference for understanding the microstructures of pharmaceutical preparations,offering new insights and potential advancements in their development.展开更多
Ensuring the removal of host cell proteins(HCPs) during downstream processing of recombinant proteins such as monoclonal antibodies(m Abs) remains a challenge.Since residual HCPs might affect product stability or safe...Ensuring the removal of host cell proteins(HCPs) during downstream processing of recombinant proteins such as monoclonal antibodies(m Abs) remains a challenge.Since residual HCPs might affect product stability or safety,constant monitoring is required to demonstrate their removal to be below the regulatory accepted level of 100 ng/mg.The current standard analytical approach for this procedure is based on ELISA;however,this approach only measures the overall HCP content.Therefore,the use of orthogonal methods,such as liquid chromatography-mass spectrometry(LC-MS),has been established,as it facilitates the quantitation of total HCPs as well as the identification and quantitation of the individual HCPs present.In the present study,a workflow for HCP detection and quantitation using an automated magnetic bead-based sample preparation,in combination with a data-independent acquisition(DIA) LC-MS analysis,was established.Employing the same instrumental setup commonly used for peptide mapping analysis of m Abs allows for its quick and easy implementation into pre-existing workflows,avoiding the need for dedicated instrumentation or personnel.Thereby,quantitation of HCPs over a broad dynamic range was enabled to allow monitoring of problematic HCPs or to track changes upon altered bioprocessing conditions.展开更多
Near infrared(NIR)spectroscopy is now widely used influidized bed granulation.However,there are still some demerits that should be overcome in practice.Valid spectra selection during modeling process is now a hard nut...Near infrared(NIR)spectroscopy is now widely used influidized bed granulation.However,there are still some demerits that should be overcome in practice.Valid spectra selection during modeling process is now a hard nut to crack.In this study,a novel NIR sensor and a cosine distance method were introduced to solve this problem in order to make thefluidized process into"visualization".A NIR sensor wasfixed on the side of the expansion chamber to acquire the NIR spectra.Then valid spectra were selected based on a cosine distance method to reduce the influence of dynamic disturbances.Finally,spectral pretreatment and wavelength selection methods were investigated to establish partial least squares(PLS)models to monitor the mois-ture content.The results showed that the root mean square error of prediction(RMSEP)was 0.124%for moisture content model,which was much lower than that without valid spectra selection treatment.All results demonstrated that with the help of valid spectra selection treatment,NIR sensor could be used for real-time determination of critical quality attributes(CQAs)more accurately.It makes the manufacturing easier to understand than the process parameter control.展开更多
Pharmaceutical production is changing from batch production to continuous production,during which granulation is one of the most important unit operations.The quality of mass-produced products is traditionally guarant...Pharmaceutical production is changing from batch production to continuous production,during which granulation is one of the most important unit operations.The quality of mass-produced products is traditionally guaranteed by conducting off-line testing,which cannot meet the demand of continuous production for real-time monitoring of critical process parameters and critical quality attributes(CQAs)of the pharmaceutical granulation technology.Since the U.S.Food and Drug Administration proposed process analytical technology(PAT)in 2004,many PAT tools have been developed to monitor the granulation process and provide information regarding the granulation operation conditions and endpoint determination.In this article,we review the recent research and application of two PAT modes in the granulation process,namely,single CQA and multi-CQA PAT,with the aim to provide references for comprehensively improving the technological level of the pharmaceutical granulation process.Furthermore,the potential applications in traditional Chinese Medicine are discussed.展开更多
This study reported an original end-to-end dataflow engineering framework for the quality transfer principle to overcome the quality challenges in real-world honey manufacturing.Firstly,650 pivotal data points of phys...This study reported an original end-to-end dataflow engineering framework for the quality transfer principle to overcome the quality challenges in real-world honey manufacturing.Firstly,650 pivotal data points of physical and chemical quality attributes from 65 batches of honey intermediates were characterized through multiple sensors,which included rheological properties,acidity,moisture,and sugars.Furthermore,a hypersensitized TAS1R2@AuNPs/SPCE biosensor was developed to identify biological quality attributes of honey,the powerful affinities between honey intermediates and the TAS1R2 receptor were discovered(KD<1×10^(−8)M),and the abnormal batches of B2,B23 and C23 were diagnosed by TAS1R2@AuNPs/SPCE biosensor and multivariable algorithm.Finally,the end-to-end dataflow containing physical,chemical and biological critical quality attributes was successfully established to interpret the quality transfer principle of honey manufacturing,which revealed that the front-end refining process was relatively unstable and the back-end refining process was a negligible influence on the quality of honey manufacturing.This framework embraces quality management,quality transfer,and biosensor information,which will contribute to discovering the quality transfer principle in industrial innovation for intelligent manufacturing.展开更多
Monitoring critical quality attributes in pharmaceutical manufacturing ensures that the final product meets specified requirements.Process analysis allows for appropriate modifications and customization of pharmaceuti...Monitoring critical quality attributes in pharmaceutical manufacturing ensures that the final product meets specified requirements.Process analysis allows for appropriate modifications and customization of pharmaceutical design from formulation to production.The laborious sample presentation and throughput have stimulated the development of in-process spectroscopy methods for pharmaceutical analysis.Raman spectroscopy has demonstrated the unique advantages of rapid and nondestructive analysis,good interpretability,and effective moisture interference avoidance.The Raman imaging technique can obtain spatial and chemical information that is useful for characterizing drug quality.This article describes the applications of Raman spectroscopy and imaging techniques in pharmaceutical analysis.It covers the monitoring of crystal forms and particle size distribution,quantification of active pharmaceutical ingredients,evaluation of contents uniformity,prediction of dissolution profiles in solid preparations,identification of counterfeit drugs,and applications in reverse engineering and process analytical technology.Moreover,the challenges and prospects are proposed to facilitate the continued development of Raman spectroscopy and imaging techniques,providing necessary references for further research in this field.展开更多
基金Project FIS PI-17/00547(Instituto CarlosⅢ,Ministerio de Economía y Competitividad,Spain),which means that it was also partially supported by European Regional Development Funds(ERDF)the University of Granada(Spain)for the support。
文摘COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest that cytokine storms(interleukins)may play an important role in severe cases of COVID-19.Neutralizing key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality rate.Tocilizumab(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS patients.Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical trials.This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug shortages.Here,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of TCZ.It is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.
基金Supported by Taishan Scholar Special Funding,No.tsqnz20240858Medical and Health Technology Project of Shandong Province,No.202402050122+4 种基金Science and Technology Development Plan of Jinan Municipal Health Commission,No.2024301008Clinical Medical Science and Technology Innovation Program of Jinan Science and Technology Bureau,No.202430055Natural Science Foundation of Jiangxi Province,No.20224BAB206077Gansu Provincial Hospital Intra-Hospital Research Fund Project,No.22GSSYB-6and the 2022 Master/Doctor/Postdoctoral Program of National Health Commission Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor,No.NHCDP2022004 and No.NHCDP2022008.
文摘Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments.The application of mesenchymal stem/stromal cells(MSCs)as therapeutic drugs has provided novel treatment options for diverse degenerative and chronic diseases including KOA.However,the complexity and specificity of the“live”cells have posed challenges for MSC-based drug development and the concomitant scale-up preparation from laboratory to industrialization.For instance,despite the considerable progress in ex vivo cell culture technology for fulfilling the robust development of drug conversion and clinical trials,yet significant challenges remain in obtaining regulatory approvals.Thus,there’s an urgent need for the research and development of MSC drugs for KOA.In this review,we provide alternative solution strategies for the preparation of MSC drugs on the basis of the principle of quality by design,including designing the cell production processes,quality control,and clinical applications.In detail,we mainly focus on the quality by design method for MSC manufacturing in standard cell-culturing factories for the treatment of KOA by using the Quality Target Product Profile as a starting point to determine potential critical quality attributes and to establish relationships between critical material attributes and critical process parameters.Collectively,this review aims to meet product performance and robust process design,and should help to reduce the gap between compliant products and the production of compliant good manufacturing practice.
基金sponsored by Natural Science Foundation of Shanghai(18ZR1439800,18ZR1436600)Three-year Action Plan for the Development of Traditional Chinese Medicine of Shanghai Municipal Health Planning Commission(ZY(2018-2020)-CCCX2001-03)+2 种基金Xinglin Young Scholar Program of Shanghai University of Traditional Chinese Medicine(A1-U17205010416)the Clinical Research Fund of Shanghai Municipal Health Commission(201940296)Science and Technology Innovation Project in Traditional Chinese Medicine of Pudong New District(PDZY2021-0813)。
文摘In recent years,new preparations of traditional Chinese medicines(TCMs)have been developed,increasing the need for their clinical trials.Using placeboes rather than control drugs is increasingly popular in clinical trials of TCMs,as the therapeutic effects of the tested TCMs can be more properly judged.The basic attributes of TCM placeboes include similarity,safety,applicability and controllability.In particular,it is necessary to have similarities in appearance,color,smell and taste between the tested TCMs and placeboes.This is quite difficult for some TCMs due to their distinctive smell and taste.On the other hand,according to the TCM theory on homology of medicine and food,many foods also have certain bioactivities,potentially further complicating the selection of materials for TCM placeboes.In this review,firstly,studies on the special smell and taste of TCMs were introduced.Then,the preparation quality evaluation processes for TCM placeboes were summarized and discussed,based on the relevant literature published in recent years and the research results from our own lab.This review will facilitate the further research and development of TCM placeboes.
基金Hunan University of Traditional Chinese Medicine Graduate Training Quality Engineering Project(2019CX57)the First-class Discipline Project on Chinese Pharmacology of Hunan University of Chinese Medicine (201803)。
文摘Objective This study aimed to design and optimize the water extraction process for Chuantieling(喘贴灵,CTL)based on the concept of quality by design(QbD).Methods The single-factor experiments were used to select the best experimental points of CTL water extraction.On this basis,the transfer rate of ephedrine hydrochloride and sin-apine thiocyanate,and the yield of the extract were evaluated as the evaluation indicators.The liquid-solid ratio,extraction time,and pH value were selected as the main factors to carry out the Box-Behnken design(BBD).A mathematical model of the critical process parameters(CPPs)and critical quality attributes(CQAs)was established,the interaction between CQAs and CPPs was examined,and the CTL extraction process design space was established and optimized,which guaranteed the stability of the process.The high performance liquid chro-matography(HPLC)was used to analyze the main active compounds in the CTL extract.Results Through single-factor experiments,the best experimental parameters were found to be a liquid-solid ratio of 8∶1,extraction time of 90 min,pH value of 4,and extraction times of three.The experimental variance analysis results of the BBD showed that the P value of the re-gression model was less than 0.05,and the lack-of-fit value was greater than 0.01,indicating that the constructed model had good predictive ability.The operating space of the CPPs of the CTL water extraction process was combined with the actual production situation.In the pro-duction situation,the best extraction process was nine times of water addition,72 min of ex-traction time,and 4.5 of pH value.The HPLC results showed that the peak areas of ephedrine hydrochloride,sinapine thiocyanate,tetrahydropalmatine,methyl eugenol,cinnamaldehyde,and 6-gingerol in the CTL extract accounted for 0.94%,14.32%,0.78%,31.23%,0.34%,and 0.44%of the total peak area,respectively.Conclusion The water extraction process design space of CTL based on QbD was conducive to actual production operations,ensuring the stability of the process.
文摘The microstructures of pharmaceutical preparations play a pivotal role in determining their critical quality attributes(CQAs),such as drug release,content uniformity,and stability,which greatly impact the safety and efficacy of drugs.Unlike the inherent molecular structures of active pharmaceutical ingredients(APIs)and excipients,the microstructures of pharmaceutical preparations are developed during the formulation process,presenting unique analytical challenges.In this review,we primarily focus on presenting the research methods used to elucidate the microstructures of pharmaceutical preparations,including X-ray imaging(XRI),scanning electron microscopy(SEM),atomic force microscopy(AFM),Raman spectroscopy,infrared(IR)spectroscopy,and rheometer technology.Subsequently,we highlight the applications,advantages,and limitations of these methods.Finally,we discuss the current challenges and future perspectives in this field.This review aims to provide a comprehensive reference for understanding the microstructures of pharmaceutical preparations,offering new insights and potential advancements in their development.
基金funding from Thermo Fisher Scientific as part of a funded collaborative agreement with NIBR。
文摘Ensuring the removal of host cell proteins(HCPs) during downstream processing of recombinant proteins such as monoclonal antibodies(m Abs) remains a challenge.Since residual HCPs might affect product stability or safety,constant monitoring is required to demonstrate their removal to be below the regulatory accepted level of 100 ng/mg.The current standard analytical approach for this procedure is based on ELISA;however,this approach only measures the overall HCP content.Therefore,the use of orthogonal methods,such as liquid chromatography-mass spectrometry(LC-MS),has been established,as it facilitates the quantitation of total HCPs as well as the identification and quantitation of the individual HCPs present.In the present study,a workflow for HCP detection and quantitation using an automated magnetic bead-based sample preparation,in combination with a data-independent acquisition(DIA) LC-MS analysis,was established.Employing the same instrumental setup commonly used for peptide mapping analysis of m Abs allows for its quick and easy implementation into pre-existing workflows,avoiding the need for dedicated instrumentation or personnel.Thereby,quantitation of HCPs over a broad dynamic range was enabled to allow monitoring of problematic HCPs or to track changes upon altered bioprocessing conditions.
基金the financial support of the Natural Science Foundation of Shandong Province of China(No.ZR2017MB012)Major In-novation Project of Shandong Province of China(2018CXGC1405)
文摘Near infrared(NIR)spectroscopy is now widely used influidized bed granulation.However,there are still some demerits that should be overcome in practice.Valid spectra selection during modeling process is now a hard nut to crack.In this study,a novel NIR sensor and a cosine distance method were introduced to solve this problem in order to make thefluidized process into"visualization".A NIR sensor wasfixed on the side of the expansion chamber to acquire the NIR spectra.Then valid spectra were selected based on a cosine distance method to reduce the influence of dynamic disturbances.Finally,spectral pretreatment and wavelength selection methods were investigated to establish partial least squares(PLS)models to monitor the mois-ture content.The results showed that the root mean square error of prediction(RMSEP)was 0.124%for moisture content model,which was much lower than that without valid spectra selection treatment.All results demonstrated that with the help of valid spectra selection treatment,NIR sensor could be used for real-time determination of critical quality attributes(CQAs)more accurately.It makes the manufacturing easier to understand than the process parameter control.
基金the National Natural Sciences Foundation of China(No.82074276)Tianjin Science and Technology project(No.20ZYJDJC00090).
文摘Pharmaceutical production is changing from batch production to continuous production,during which granulation is one of the most important unit operations.The quality of mass-produced products is traditionally guaranteed by conducting off-line testing,which cannot meet the demand of continuous production for real-time monitoring of critical process parameters and critical quality attributes(CQAs)of the pharmaceutical granulation technology.Since the U.S.Food and Drug Administration proposed process analytical technology(PAT)in 2004,many PAT tools have been developed to monitor the granulation process and provide information regarding the granulation operation conditions and endpoint determination.In this article,we review the recent research and application of two PAT modes in the granulation process,namely,single CQA and multi-CQA PAT,with the aim to provide references for comprehensively improving the technological level of the pharmaceutical granulation process.Furthermore,the potential applications in traditional Chinese Medicine are discussed.
基金co-supported by Excellent Young Scientists Fund of National Natural Science Foundation of China(82022073)Major scientific and technological R&D projects in Jiangxi Province(20203ABC28W018)+1 种基金National Natural Science Foundation of China(82274110)the Fundamental Research Funds for the Central Universities(2022-JYB-JBZR-018,2022-JYB-JBZR-019).
文摘This study reported an original end-to-end dataflow engineering framework for the quality transfer principle to overcome the quality challenges in real-world honey manufacturing.Firstly,650 pivotal data points of physical and chemical quality attributes from 65 batches of honey intermediates were characterized through multiple sensors,which included rheological properties,acidity,moisture,and sugars.Furthermore,a hypersensitized TAS1R2@AuNPs/SPCE biosensor was developed to identify biological quality attributes of honey,the powerful affinities between honey intermediates and the TAS1R2 receptor were discovered(KD<1×10^(−8)M),and the abnormal batches of B2,B23 and C23 were diagnosed by TAS1R2@AuNPs/SPCE biosensor and multivariable algorithm.Finally,the end-to-end dataflow containing physical,chemical and biological critical quality attributes was successfully established to interpret the quality transfer principle of honey manufacturing,which revealed that the front-end refining process was relatively unstable and the back-end refining process was a negligible influence on the quality of honey manufacturing.This framework embraces quality management,quality transfer,and biosensor information,which will contribute to discovering the quality transfer principle in industrial innovation for intelligent manufacturing.
基金financial support of Key Project of Tianjin Natural Science Foundation(23JCZDJC00720)S&T Project of Haihe Laboratory of Modern Chinese Medicine(22HHZYSS00004)+1 种基金the Key University Science Research Project of Anhui Province(KJ2021A1146,KJ2020A0775)first batch of provincial science and technology mission projects in Anhui Province(2023tpt014)。
文摘Monitoring critical quality attributes in pharmaceutical manufacturing ensures that the final product meets specified requirements.Process analysis allows for appropriate modifications and customization of pharmaceutical design from formulation to production.The laborious sample presentation and throughput have stimulated the development of in-process spectroscopy methods for pharmaceutical analysis.Raman spectroscopy has demonstrated the unique advantages of rapid and nondestructive analysis,good interpretability,and effective moisture interference avoidance.The Raman imaging technique can obtain spatial and chemical information that is useful for characterizing drug quality.This article describes the applications of Raman spectroscopy and imaging techniques in pharmaceutical analysis.It covers the monitoring of crystal forms and particle size distribution,quantification of active pharmaceutical ingredients,evaluation of contents uniformity,prediction of dissolution profiles in solid preparations,identification of counterfeit drugs,and applications in reverse engineering and process analytical technology.Moreover,the challenges and prospects are proposed to facilitate the continued development of Raman spectroscopy and imaging techniques,providing necessary references for further research in this field.
