Quality By Design Concept Research Articles

Analytical Method Lifecycle Management in Pharmaceutical Industry: a Review.

The adoption of Quality by Design (QbD) and Analytical Method Lifecycle Management (AMLM) concepts to ensure the quality of pharmaceutical products has been applied and proposed over the last few years. These concepts are based on knowledge gained from the application of scientific and quality risk management approaches, throughout method lifecycle to assure continuous improvement and high reliability of analytical results. The overall AMLM starts with the definition of the method's intended use through the Analytical Target Profile definition, including three stages: (1) Method Design, taking advantage of the well-known concept of QbD; (2) Method Performance Qualification; (3) Continued Method Performance Verification. This is intended to holistically align method variability with product requirements, increasing confidence in the data generated, a regulatory requirement that the pharmaceutical industry must follow. This approach views all method-related activities, such as development, validation, transfer, and routine use as a continuum and interrelated process, where knowledge and risk management are the key enablers. An increase in method robustness, cost reduction, and decreased risk failures are some of the intrinsic benefits from this lifecycle management. This approach is clearly acknowledged both by regulators and industry. The roadmap of the regulatory and industry events that mark the evolution of these concepts helps to capture the current and future expectation of the pharmaceutical framework.

Quality by Design (QbD): Application of Comprehensive Risk Analysis in Blending Process for XLGB Capsule in Medicine Industry

Intelligent development is becoming an inevitable choice for the development of green manufacturing enterprises, improving the medical quality and guaranteeing the safety is an important role player in the intelligent development of medical industry. Since the risk model prediction is crucial in many areas of medical work, risk management and communication are meaningful in industry management. The framework of comprehensive risk management of Chinese Patent Medicine (CPM) has been presented and constructed at presence. To enhance the quality level and safety management of medical service, this article explored the different theory meanings of innovation and conducted a comprehensive risk evaluation of Chinese medicine industry. This paper provides a foundational reference for future research that how to apply quality-by-design (QbD) approach for the development of medicine industry. This study demonstrates that the application of the QbD concept is a novel area in CPM quality.

Solid State Characterization of Olmesartan medoximil Solid Dispersion and in-silico Formulation Design using Quality by Design Techniques Engendered by Definitive Screening Design

Objectives: Olmesartan medoxomil (OM) is employed for treating patients who are intolerant of ACE inhibitors. The challenge to the researchers is because of its poor oral bioavailability and poor solubility. The approach for this problem is to use a hydrophilic carrier in formulation of oro-dispersible tablet (ODT) which presents a suitable way to improve the bioavailability by using quality by design (QbD) techniques with design of experiments (DoE) using definitive screening design (DSD) which produce a robust and rugged formulation. Methods: The focus of the research was to formulate OM/PVP solid dispersion (SD) and formulation of an Oro dispersible tablet (ODT) by QbD techniques. The main focus of this research is to provide a rugged and robust formulation using QbD concept with the application of Definitive screening design for optimization. Results: The dissolution studies of OM/PVP K30 1:1% w/w showed full release within 30 min which may be attributed due to the hydrogen bond formation between OM and PVP K30 in the FTIR spectra which enhanced the solubility. The disintegration and dissolution results were found to be satisfactory and meeting the desired quality target product profile (QTPP). Conclusion: The present research highlights a thorough understanding of the dosage form development with the knowledge of the critical risks involved in formulation to have an impact on critical quality attributes (CQAs). The critical material attributes (CMAs) were refined by DoE using definitive screening design (DSD) to develop design space. Key words: Critical material attributes (CMAs), Critical quality attributes (CQAs), Definitive screening design (DSD), Quality by design (QbD), Design of experiments (DoE).

Implementation of the Quality by Design approach for developing the composition and the manufacturing technology of an injectable drug for intra-articular introduction

Aim. To implement the Quality by Design (QbD) approach in order to develop the composition and the manufacturing technology of injectable hyaluronate sodium (HS) in combination with chondroitin sulfate (CS) for intra-articularintroduction. Materials and methods. The composition of the solution for injection was developed using samples of the active pharmaceutical ingredient (API) of HS and CS. The approaches of the ICH international guidelines were used to create the QbD protocol. The quality target product profile (QTPP) was developed based on the literature review, analysis of similar drugs and the previous in-house experimental studies. Determination of critical quality assessment (CQA) product indicators was performed by risk analysis for all quality indicators listed in QTPP. The risk assessment of quality indicators was performed by assessing them according to the Risk Priority Number system (hereinafter – RPN) by a 9-point scale. When studying the composition and the manufacturing technology of the injectable solution the quality risk management (QRM) was developed according to the Ishikawa diagram. Results and discussion. It has been found that the QbD concept is a systematic approach to the drug development. At the first stage QTPP was developed. Based on the QTPP data the CQA indicators were determined, and quality risks were assessed. The critical process parameters (CPP) of the solution for injection based on HS and CS, their control methods, as well as the critical material attributes (CMA) were determined. Based on the data obtained the drug control strategy was proposed taking into account the need to minimize the repetition of control experiments. Using the Isikawa diagram the variability of the material and the process with the environmental factors affecting the qualityof the solution for injection with HS and CS was shown.Conclusions. Using the basic QbD approaches when developing the composition and the manufacturing technology of an injectable drug for intra-articular introduction it has been found that the route of administration, dose, potency, and consumer properties of the product are important aspects of QTPP. It has been proven that the quality indicators, such as transparency, viscosity, sterility and the quantitative content of API are determined as CQA to achieve the objectives defined in QTPP. The study shows that almost all stages of production are critical, therefore, they need to be constantly monitored and checked to obtain a quality product. In further experimental studies to confirm the composition developed and the manufacturing technology according to QRM it is necessary to focus on such indicators as the solution temperature, stabilization time, degassing mode and filtration conditions.

A strategy for population pharmaceutical quality assessment based on quality by design

From a regulatory perspective, drug quality consistency evaluation must concern different processes used for the same drug. In this study, an assessment strategy based on quality by design (QbD) was developed for population pharmaceutical quality evaluation. A descriptive analysis method based on QbD concept was first established to characterize the process by critical evaluation attributes (CEAs). Then quantitative analysis method based on an improved statistical process control (SPC) method was established to investigate the process indicators (PIs) in the process population, such as mean distribution, batch-to-batch difference and abnormal quality probability. After that rules for risk assessment were established based on the SPC limitations and parameters. Both the SPC parameters of the CEAs and the risk of PIs were visualized according to the interaction test results to obtain a better understanding of the population pharmaceutical quality. Finally, an assessment strategy was built and applied to generic drug consistency assessment, process risk assessment and quality trend tracking. The strategy demonstrated in this study could help reveal quality consistency from the perspective of process control and process risk, and further show the recent development status of domestic pharmaceutical production processes. In addition, a process risk assessment and population quality trend tracking provide data-based information for approval. Not only can this information serve as a further basis for decision-making by the regulatory authority regarding early warnings, but it can also reduce some avoidable adverse reactions. With continuous addition of data, dynamic population pharmaceutical quality is meaningful for emergencies and decision-making regarding drug regulation.

Development of preparation process of icaritin-coix seed oil microemulsion based on quality by design concept

To optimize the formulation and preparation process of icaritin-coix seed oil microemulsion(IC-MEs) based on quality by design(QbD) concept. IC-MEs were prepared by water titration. Firstly, the risk factors that may affect the quality of IC-MEs were evaluated. Then Plackett-Burman design was used to screen out prescription factors and process parameters that had a significant effect on the indicators. Finally, Box-Behnken design was used to optimize the prescription ratio of IC-MEs. Through the risk assessment and Plackett-Burman design, three formulation factors [drug loading efficiency, the ratio of mixed-oil(coix seed oil-Glycerol tributyrate) to mixed-surfactant(HS15-RH40) and water addition] were determined as the key factors affecting IC-MEs. The regression model established by Box-Behnken design had a good predictability. The optimal formula was as following: the drug loading efficiency of 0.92%, the ratio of mixed-oil(coix seed oil-glycerol tributyrate) to mixed-surfactant(HS15-RH40) of 4∶6, and the water addition of 5.7 mL. According to this prescription, IC-MEs were prepared, and its encapsulation efficiency after 1 week was 92.45%±1.00%. Therefore, the stability of IC-MEs could be improved by optimizing prescription and process parameters of IC-MEs based on the QbD concept, which can provide certain reference value for the future development of IC-MEs.

Analytical Quality by Design as an Important Tool to Determine the Best Analytical Conditions for Isoniazid and Its Respective Succinylated Prodrug.

Tuberculosis is a worldwide health concern and isoniazid is the most used and considered one of the most effective drugs for its treatment. The "quality" concept must be incorporated into the final pharmaceutical product, according to the quality by design (QbD) definition. Therefore, the determination of analytical test conditions is extremely important and the design of experiments (DoE) becomes a very useful tool. This paper used the concept of QbD to assist the development of analytical conditions for isoniazid and its respective prodrug, applying HPLC. HPLC analytical methodologies were developed for isoniazid and its succinylated derivative. The experimental design was carried out using three analytical parameters at three levels. Four chromatographic responses were studied. The impact of analytical parameters on chromatographic responses was assessed using a Pareto chart. Regression models were obtained using multiple regression analysis. DoE analysis was conducted using the Minitab® program and the experiments were performed sequentially, with varying factors. We identify three main risk parameters: mobile phase (high), flow rate (moderate), and pH of buffer (moderate). The ratio of mobile phase buffer (X2) and mobile phase pH (X3) had a major influence on the peak resolutions (Y3). The capacity factors for iso-suc (Y1) and isoniazid (Y2) peaks should be within 3-9 and 4-10, respectively. The peak resolutions between iso-suc and isoniazid (Y3) should be above two. We designed 27 experiments, obtaining 1.0 mL/min flow rate, 95% buffer in the mobile phase, and pH 7.0 as the optimal analytical conditions. Analytical Quality by Design was used as an important tool to determine the best analytical test conditions for isoniazid and its respective prodrug - succinylated isoniazid.

The application of quality by design in the development of the liquid chromatography method to determine empagliflozin in the presence of its organic impurities.

Analysis of impurities is an important step in the quality control of pharmaceutical ingredients and final products. From drug synthesis or excipients, even in small concentrations, impurities may affect efficacy and safety. The method was developed following Quality by Design (QbD) for the analysis of the antidiabetic empagliflozin. The concept of QbD is used as a tool for the development of methods and formulations. Through predefined objectives and risk analysis, robust methodologies and reduced solvent consumption are developed. A simple HPLC method was developed and validated for the quantitative determination of empagliflozin and its organic impurities from the synthesis process. The method was carried out in a Shim-pack phenyl column with a mobile phase consisting of an acetonitrile/water mixture (72 : 28), with isocratic elution and the detector wavelength was 230 nm. The validation process, in accordance with international guidelines, shows that the method was linear, precise and accurate for empagliflozin, impurity 1 and impurity 2. Limits of detection (0.01, 0.02 and 0.01 μg mL−1) and quantification (0.10, 0.10 and 0.05 μg mL−1) were determined for EMPA, IMP1 and IMP2, respectively. The HPLC method for impurity determination in empagliflozin was linear, precise, accurate and robust. It can be successfully applied in the quality control of empagliflozin and the synthesis of impurities, being adequate for routine analysis.

Considerations and Regulatory Challenges for Innovative Medicines in Expedited Approval Programs: Breakthrough Therapy and Sakigake Designation.

In the breakthrough therapy designation (BTD) and Sakigake designation programs, rolling submission and close communication between applicants and regulatory authorities enable the timely access of patients to innovative medicines. However, challenges in the quality development, including chemistry, manufacturing, and control (CMC), are expected during the accelerated timeline. This study focused on development with quality by design (QbD) concept, shelf life of drug product, and post marketing commitment (PMC) to clarify developmental strategies and regulatory challenges associated with expedited approval programs. QbD developments, shelf life of drug products, and PMC were surveyed in the review reports of the US Food and Drug Administration (FDA) and Pharmaceuticals and Medical Devices Agency (PMDA) websites. Overall, 86% of BTD products and two out of three Sakigake products were developed using a QbD approach. Furthermore, 92% of BTD products and two out of three Sakigake products were granted a shelf life of at least 18months. In the BTD pathway, 50% of PMCs concerned the reevaluation of specification and test method. For most BTD and Sakigake products, the control strategy was developed utilizing the QbD concept, and long shelf life was granted despite the accelerated timeline. No discount for specification setting was observed for assuring quality, based on the available data at the time of approval in the BTD and Sakigake programs, although PMCs were mainly required for reevaluation of the specification and test method in BTD programs. Further efforts should focus on creating/revising guidelines for CMC development.

Research of classical prescription based on QbD concept:optimization of extraction process for modified Siwu Decoction

As an advanced concept in international pharmaceutical research,quality by design( QbD) can fulfill the strategic requirements of drug quality from testing to design. In this paper,the extraction process of Yanggong Prescription which was the modified Siwu Decoction was optimized based on QbD concept. With the extraction amount of solid matter,the content of ferulic acid and the content of paeoniflorin as critical quality attributes( CQAs),the failure mode and effect analysis( FMEA) was used to screen potential critical process parameters( p CPPs). The mathematical model was established by Box-Behnken experimental design to investigate the interaction between critical process parameters( CPPs) and CQAs. Then the design space for the extraction process of Yanggong Prescription was further established and optimized. Analysis of variance showed that the variance of all models was significant( P<0. 01),and the lack-of-fit value was not significant,indicating that the model was statistically significant. The relationship between various factors and the response values could be functionalized by the established models. Finally,through the optimization of the design space,the optimum extraction process of Yanggong Prescription was obtained as follows: 3 extraction times,122 minutes extraction,and 7 times of water adding. The extraction process of Yanggong Prescription based on the QbD concept was robust and reliable,which would provide guidance for the process development and quality control of its formulations.

Design and development of sustained and controlled release preparations in traditional Chinese medicine based on quality by design( QbD)

In this paper,the design and development of sustained and controlled release preparations in traditional Chinese medicine( TCM) based on quality by design( QbD) was put forward,aiming at the current situation that the final product quality is affected by multiple factors during the development of sustained and controlled release preparations in TCM. The important development of sustained and controlled release preparations in western medicine in recent years was summarized. According to the complex process of TCM,the concept of QbD was proposed to design and develop sustained and controlled release preparations in TCM. QbD concept was used to analyze the complex factors affecting sustained and controlled release preparations in TCM,and determine the high risk factors affecting the quality of the final product. The high risk factors were controlled from the process to achieve the goal of quality control.This article could provide research ideas for the sustained and controlled release preparations with complex components in TCM,so as to promote the research and development of sustained and controlled release preparations in TCM.

Study on famous prescription of prestigious traditional Chinese medicine based on QbD concept: optimization of extraction process and granule forming process of Tuomin Dingchuan Prescription

The quality of compound traditional Chinese medicine is the prerequisite and foundation for its stable efficacy. Based on the quality by design( QbD) concept,the controllable extraction times,extraction time and the ratio of water were the critical process parameters( CPPs) in the Tuomin Dingchuan Prescription extraction process. The CQAs corresponding to CPPs were screened from the four potential critical quality attributes( p CQAs),namely the extraction amount of solid matter,the content of amygdalin,the content of cimicifugoside and the content of 5-O-methylvisammioside by orthogonal experiment. The extraction amount of solid matter and the content of amygdalin were determined as CQAs in the extraction process by the variance analysis of Box-Behnken experimental. The optimal extraction process based on the linear model between CQAs and CPPs of the extraction process was immersion in water for 30 minutes,extraction for three times,extraction for 100 minutes each time and 10 times of water volume. The control space was established for the extraction amount of solid matter and the content of amygdalin,and both of them could be controlled simultaneously to achieve the optimization objective. The molding ratio of Tuomin Dingchuan granules was regarded as CQA in forming process. On the basis of the single factor investigation,the ratio of dry extract powder to excipient and the ratio of ethanol were determined as CPPs. The central composite design( CCD) was used to optimize the forming process of Tuomin Dingchuan granules. The results showed that the dextrin was used as the filler; the ratio of dry paste to dextrin was 1 ∶1; and 0. 3 m L·g-1 of 70% ethanol was added as binder. The soft material and granules conformed to the actual production requirements.

Study on famous prescription of prestigious traditional Chinese medicine master Lu Zhizheng based on QbD concept: optimization of extraction process and granule forming process of Meiyan Shuqi Prescription

Based on the concept of quality by design( QbD),the design space of Meiyan Shuqi Prescription extraction process was established,and its granules forming process was optimized. The content of total flavonoids was the critical quality attribute( CQA).The amount of water,extraction time and frequency were used as the critical process parameters( CPPs). Box-Behnken experimental design was used to optimize the extraction process. The design space of Meiyan Shuqi Prescription extraction process was established and verified. The results of variance analysis showed that the P value of the quadratic regression model was less than 0. 01,which indicated that the model had a statistical significance,and the relationship between each factor and response value could be functionalized by the established model. Through further optimization of design space,the optimal extraction process of Meiyan Shuqi prescription was13-fold volume of water,extraction for 3 times and each extraction time of 1. 4 hours. Furthermore,the forming process optimized by single factor was as follows: the excipient was dextrin; the ratio of extract powder to excipient was 1 ∶1; the wetting agent was 70% ethanol; and the amount of wetting agent was 0. 3 m L·g-1. The Meiyan Shuqi Prescription extraction process and the forming process based on QbD concept provide reference for the study of other traditional Chinese medicine prescriptions.

Research of hospital preparations based on QbD concept: whole process optimization strategy of gynecological antipruritic lotion

The stable quality of hospital preparations is the basis for their clinical efficacy. Gynecological antipruritic prescription is widely used in gynecology clinics of Chinese medicine hospitals. Therefore,in this study,the production process of gynecological antipruritic lotion was optimized based on the concept of quality by design( QbD). The production process of the gynecological antipruritic lotion was developed to ensure its process stability and reliable quality,and enhance its clinical applicability. With total amount of matrine and oxymatrine used as the critical quality attribute( CQA) of the production process,parameter levels were designed based on production practice of hospital preparations,and Plackett-Burman and Box-Behnken experiments were used to optimize the water extraction and alcohol precipitation process of antipruritic lotion based on CQA of intermediates and final product. The soaking time,the first extraction time,and the second extraction time were determined as the critical process parameters( CPPs) of the production process. The optimal preparation process was as follows: water volume of 8 times,soaking for 0. 5 h,extraction for 2 times,the first extraction for 30 min,the second extraction for 56 min,alcohol concentration of 50%,and alcohol precipitation for 3 h. Furthermore,the design space was established based on the binomial regress model between CPPs and CQA,so as to set the optimization target and risk range; and the control space was displayed by overlay plot. The results of three repeated experiments in the control space showed that the relative standard deviation( RSD) of CQA was 4. 70%,and the similarity of chromatogram for gynecological antipruritic lotion was 0. 978,0. 974,and 0. 998,respectively. The above results indicated that the operation in the control space can guarantee the quality and stability of gynecological antipruritic lotion,suitable for practical application.

Implementation of Quality by Design: A Review

Background: In pharmaceutical terms, quality means a product free from any contamination and delivers the therapeutic benefit specified in the label at a reproducible rate which can be assessed by carrying out in vivo or in vitro tests for evaluation of performance. Quality by Design (QbD) is a necessary tool in pharmaceutical environment for having product/process/method impregnated with quality. QbD is a move toward drug development that ensures the preplanned product specifications by providing guidance for architecting the manufacturing processes and formulation. Methodology: It has provided the solution to support both the regulatory bodies and industry to shift towards added proactive and scientific approach. QbD is the greatest solution to construct quality in all pharmaceutical products, while at the same time, making it a part of the system is also a key challenge for the industry. By using QbD concept, regulators as well as industries are making a move in geometric progress in bringing quality products. Regulatory bodies across the world are showing significant attention to QbD. Conclusion: Therefore, an attempt has been made to highlight quality by designing generic drugs and its implications to pharmaceutical industry including clinical trials, pharmaceutical validation processes and in biologics and also to provide a brief description on the status of QbD in India and as well as in Asia.

Misunderstanding Design Space: a Robust Drug Product Control Strategy Is the Key to Quality Assurance

ICH guidelines Q8/11, Q9, and Q10 introduced risk-based approaches and enhanced scientific understanding as an opportunity to encourage continuous process improvement for pharmaceutical manufacturing. Conceptually, Quality by Design (QbD) promised to improve confidence in quality through the lifecycle of pharmaceutical products. A primary incentive for industry is the prospect of global regulatory concordance for new applications and post approval changes. Unfortunately, during the last decade, the industry has experienced regulatory divergence regarding the interpretation of ICH guidelines across geographic regions. Rather than truly harmonized regulatory expectations, localized interpretations of ICH guidance have resulted in different technical requirements posing significant challenges for a global industry. As a result, the increased complexity of manufacturing supply chains and the regulatory burden associated with maintaining compliance with these diverse regulatory expectations serves as a barrier to continual improvement and innovation. The QbD paradigm has effectively demonstrated a risk-based link between a product’s control strategy and patient needs that has prompted meaningful improvement in the industry’s approach to product quality assurance. Divergent interpretations of the concepts and definitions used in the modern QbD approach to product development and manufacturing, however, has led to challenges in achieving a common implementation of design space, control strategy, prior knowledge, proven acceptable range, and normal operating range. While the concept of design space remains an appealing focal point for demonstrating process understanding, the authors suggest that Control Strategy is the most important QbD concept, and one that assures product quality for patients. A focus by both regulators and manufacturers on the significance of Control Strategy could facilitate management of post approval changes to improve manufacturing processes and enhance product quality while also engendering regulatory harmonization.

Application of Quality by Design Approach to Bioanalysis: Development of a Method for Elvitegravir Quantification in Human Plasma.

The application of Quality by Design (QbD) principles in clinical laboratories can help to develop an analytical method through a systematic approach, providing a significant advance over the traditional heuristic and empirical methodology. In this work, we applied for the first time the QbD concept in the development of a method for drug quantification in human plasma using elvitegravir as the test molecule. The goal of the study was to develop a fast and inexpensive quantification method, with precision and accuracy as requested by the European Medicines Agency guidelines on bioanalytical method validation. The method was divided into operative units, and for each unit critical variables affecting the results were identified. A risk analysis was performed to select critical process parameters that should be introduced in the design of experiments (DoEs). Different DoEs were used depending on the phase of advancement of the study. Protein precipitation and high-performance liquid chromatography-tandem mass spectrometry were selected as the techniques to be investigated. For every operative unit (sample preparation, chromatographic conditions, and detector settings), a model based on factors affecting the responses was developed and optimized. The obtained method was validated and clinically applied with success. To the best of our knowledge, this is the first investigation thoroughly addressing the application of QbD to the analysis of a drug in a biological matrix applied in a clinical laboratory. The extensive optimization process generated a robust method compliant with its intended use. The performance of the method is continuously monitored using control charts.

Implementation of Quality by Design for Formulation of Rebamipide Gastro-retentive Tablet.

The purpose of the present study was to develop a rebamipide (RBM) gastro-retentive (GR) tablet by implementing quality by design (QbD). RBM GR tablets were prepared using a sublimation method. Quality target product profile (QTPP) and critical quality attributes (CQAs) of the RBM GR tablets were defined according to the preliminary studies. Factors affecting the CQAs were prioritized using failure mode and effects analysis (FMEA). Design space and optimum formulation were established through a mixture design. The validity of the design space was confirmed using runs within the area. The QTPP of the RBM GR tablets was the orally administered GR tablet containing 300mg of RBM taken once daily. Based on the QTPP, dissolution rate, tablet friability, and floating property were chosen as CQAs. According to the risk assessment, the amount of sustained-release agent, sublimating material, and diluent showed high-risk priority number (RPN) values above 40. Based on the RPN, these factors were further investigated using mixture design methodology. Design space of formulations was depicted as an overlaid contour plot and the optimum formulation to satisfy the desired responses was obtained by determining the expected value of each response. The similarity factor (f2) of the release profile between predicted response and experimental response was 89.463, suggesting that two release profiles are similar. The validity of the design space was also confirmed. Consequently, we were able to develop the RBM GR tablets by implementing the QbD concept. These results provide useful information for development of tablet formulations using the QbD.

Research on whole blending end-point evaluation method of Angong Niuhuang Wan based on QbD concept

The blending end-point determination of Angong Niuhuang Wan (AGNH) is a key technology problem. The control strategy based on quality by design (QbD) concept proposes a whole blending end-point determination method, and provides a methodology for blending the Chinese materia medica containing mineral substances. Based on QbD concept, the laser induced breakdown spectroscopy (LIBS) was used to assess the cinnabar, realgar and pearl powder blending of AGNH in a pilot-scale experiment, especially the whole blending end-point in this study. The blending variability of three mineral medicines including cinnabar, realgar and pearl powder, was measured by moving window relative standard deviation (MWRSD) based on LIBS. The time profiles of realgar and pearl powder did not produce consistent results completely, but all of them reached even blending at the last blending stage, so that the whole proposal blending end point was determined. LIBS is a promising Process Analytical Technology (PAT) for process control. Unlike other elemental determination technologies such ICP-OES, LIBS does not need an elaborate digestion procedure, which is a promising and rapid technique to understand the blending process of Chinese materia medica (CMM) containing cinnabar, realgar and other mineral traditional Chinese medicine. This study proposed a novel method for the research of large varieties of traditional Chinese medicines..

Research advances in secondary development of Chinese patent medicines based on quality by design concept

Quality by design (QbD) concept is an advanced pharmaceutical quality control concept. The application of QbD concept in the research and development of pharmaceutical processes of traditional Chinese medicines (TCM) mainly contains five parts, including the definition of critical processes and their evaluation criteria, the determination of critical process parameters and critical material attributes, the establishment of quantitative models, the development of design space, as well as the application and continuous improvement of control strategy. In this work, recent research advances in QbD concept implementation methods in the secondary development of Chinese patent medicines were reviewed, and five promising fields of the implementation of QbD concept were pointed out, including the research and development of TCM new drugs and Chinese medicine granules for formulation, modeling of pharmaceutical processes, development of control strategy based on industrial big data, strengthening the research of process amplification rules, and the development of new pharmaceutical equipment..