Formulation and technology of oxymatrine-astragaloside IV coloaded liposomes based on quality by design / 药学学报

To optimize the formulation and technology of oxymatrine-astragaloside IV coloaded liposomes (Om-As-Lip) based on quality by design (QbD) principles, and further to verify the feasibility of its amplification process, Om-As-Lip was prepared by ethanol injection combined with pH gradient method. The critical material attributions of Om-As-Lip were evaluated by dual-risk analysis tools and Plackett-Burman design (PBD). The formulation of Om-As-Lip was further optimized with the Box-Behnken design (BBD). The design space was also established based on the contour plots of BBD. In order to further investigate the amplification process of Om-As-Lip, the critical process parameters of high-pressure homogenization (HPH) were optimized by single-factor test, and the quality of the final product was also evaluated. The results of risk analysis and PBD confirmed that the astragaloside concentration, cholesterol concentration, and phospholipid ratio (HSPC∶SPC) were the ctitical material attributes. The model established by BBD had a good predictability, and the optimized mass ratio of As to phospholipids was 1∶40, cholesterol to phospholipids was 1∶10, HSPC to SPC was 51∶9. The design space of Om-As-Lip was as follows: the ratio of cholesterol to phospholipids was 1∶12-1∶5 and HSPC to SPC was 1∶7-17∶3. The optimized high-pressure homogenization pressure was 600 bar, temperature was 4 ℃, and cycle times was 6 times for HPH-Om-As-Lip. The quality of Om-As-Lip prepared based on the QbD concept can meet the expected CQAs, and the formulation and technology established can provide a reliable experimental basis for its future development and applications.

Four critical engineering and technical problems in manufacturing measurement of traditional Chinese medicine / 中国中药杂志

Focusing on the development and quality improvement strategy of the traditional Chinese medicine(TCM) industry, the scientific and technological innovation of the new engineering of TCM should be paid attention to solve the "stuck neck" dilemma. Under the background of the ecological and industrial revolution of the scientific and technological innovation system, the super-scale information interaction and multi-dimensional integration will inevitably lead to profound changes in the manufacturing mode of TCM. Manufacturing measurement of TCM is formed on the basis of the reliability engineering theory of process control of TCM production. It is the development extension of system theory and system science ideas and a cross-fertilization discipline that combines theory with practice and adheres to the "four-oriented" re-epistemology improvement of the TCM discipline. In response to the problems of complex raw material sources, coarse process technology, unclear material basis, and poor applicability of equipment and technology in the manufacture of TCM, the transformation research mode of "aiming at the integration of pharmaceutical industry-developing intelligent production line-enabling industrial transformation" has been developed. This paper proposed the four key engineering technical problems, i.e., the identification of critical quality attributes(CQA) in the manufacture of TCM, the quality by design(QbD) and product development of the manufacturing process of TCM, the quality transfer principle and multivariate process capability index of TCM manufacturing, and the development of measurement technology and equipment of the manufacturing measurement of TCM, to achieve the systematization of quality control indicators, real-time process control, digitalization of manufacturing process, transparency of quality transfer, and intelligent whole-process control. In this paper, the new concepts, new theories, and new technologies provide a reference for the industrialization of TCM.

Discussion on Microbial Quality Control Strategy in Whole Process of Chinese Materia Medica Production Guided by Concept of QbD / 中国实验方剂学杂志

Safety is the core of the quality of Chinese materia medica products， and microbial pollution caused by medicinal materials， decoction pieces， intermediate products and others can bring certain impact on the quality and safety of Chinese materia medica products. The reasons for this are not only the problems of medicinal materials themselves， but also the exogenous pollution introduced in the production process. How to effectively use microbial detection technology and establish an appropriate microbial quality control strategy in the whole process of Chinese materia medica production is of great significance to improve the quality of Chinese materia medica products. Therefore， the authors put forward a microbial quality control strategy in the whole process of Chinese materia medica production based on the guidance of quality by design （QbD） concept， emphasizing the scientific linkage between the internal and external microbial quality control systems to jointly ensure the quality of products in all aspects. Among them， the internal microbial quality control system includes the control of the whole chain of Chinese materia medica-decoction pieces-intermediate products-excipitents-packaging materials-final products， which should be carried out by stages and characteristics， while the external microbial quality control system includes the control of personnel-equipment and facilities-pharmaceutical water-environment， emphasizing the principle of quality risk management and the development of monitoring programs， aiming to closely integrate microbial quality risk management with the production process of Chinese materia medica products， and to classify and develop microbial control strategies in order to minimize the impact of contaminating microorganisms and effectively guarantee the quality of Chinese materia medica products.

Preparation of 3D printed metoprolol tartrate chewable tablets and optimization of printing process / 药学学报

With the growing demand of personalized medicine for children, it is especially important to develop medicines for children. In this study, using metoprolol tartrate as model drug, we developed 3D printed chewable tablets suitable for children with automated dosage distribution using semi-solid extruded (SSE) 3D printing technology. Based on the quality by design concept, this study prepared a semi-solid material with good printability using gelatin as the substrate, constructed 3D models and printed tablets with the aid of computer-aided design. The printing parameters were optimized and determined as follows: print temperature of 35-37 ℃, print speed of 25 mm·s-1, fill rate of 15%, and number of outer profile layers of 2. Subsequently, the printing process and the quality uniformity of the tablets were verified, and a linear relationship between the dose and the number of model layers was obtained. Finally, 3D printed chewable tablets were superior in terms of appearance, dose accuracy and compliance compared with traditional split-dose commercially available tablets. In this study, 3D printed metoprolol tartrate chewable tablets with good performance were successfully prepared to address the personalized medication needs of pediatric patients.

Quality by Design approach for the investigation of critical characteristics of Phyllanthus emblica from different vicinities / 数字中医药（英文）

@#[Objective] To explore the application of Quality by Design (QbD) tools in assessing geographical variations of Phyllanthus emblica (P. emblica) from five distinct Indian states. [Methods] In the current experiment, the Box-Behnken design with a reduced quartic model and 105 runs was employed with the use of the Design Expert software for randomized response surface mapping. Three different extraction methods (Soxhlet, maceration, and sonication) along with three solventst [distilled water, methanol, and water-methanol mixture (50 : 50 v/v)] were considered in the present study. The anti-oxidant activities, total flavonoid content (TFC), and total phenolic content (TPC) in the P. emblica were determined and analysed by gas chromatography-mass spectrometry (GC-MS) to identify the major components. [Results] The QbD overlay plot showed that the extractive value of the P. emblica was no less than 30% w/w, 2,2-diphenyl-1-picrylhydrazyl (DPPH) no less than 60% mcg/mL (micrograms per millilitre), TFC no less than 75 mg QE/g (milligrams of quercetin equivalents per gram), and TPC no less than 80 mg GAE/g (milligrams of gallic acid equivalents per gram). Moreover, the GC-MS data confirmed the presence of variation in the bioactives of P. emblica extracts. [Conclusion] The model was significant in describing the variation in extractive value, DPPH, TFC, and TPC. The QbD approach may tend to prioritize thoroughness in the extraction process, ultimately resulting in improved quality in the extracted products.

Optimization of HPLC method using central composite design for estimation of Torsemide and Eplerenone in tablet dosage form

Abstract A simple, precise, accurate and robust high performance liquid chromatographic method has been developed for simultaneous estimation of Torsemide and Eplerenone in tablet dosage form. Design of experiment was applied for multivariate optimization of the experimental conditions of RP-HPLC method. A Central composite design was used to study the response surface methodology and to analyse in detail the effects of these independent factors on responses. Total eleven experiments along with 3 center points were performed. Two factors were selected to design the matrix, one factor is variation in ratio of Acetonitrile and the second factor is flow rate (mL/min). Optimization in chromatographic conditions was achieved by applying Central composite design. The optimized and predicted data from contour diagram comprised mobile phase (acetonitrile, water and methanol in the ratio of 50: 30: 20 v/v/v respectively), at a flow rate of 1.0 ml/min and at ambient column temperature. Using these optimum conditions baseline separation of both drugs with good resolution and run time of less than 5 minutes were achieved. The optimized assay conditions were validated as per the ICH guidelines (2005). Hence, the results showed that the Quality by design approach could successfully optimize RP-HPLC method for simultaneous estimation of Torsemide and Eplerenone.

Spray Drying in Research of Traditional Chinese Medicine Powders： A Review / 中国实验方剂学杂志

After more than 100 years of development， spray drying technology has become more mature and widely used， and it is of great importance in the field of traditional Chinese medicine （TCM）. TCM powders prepared by spray drying is the raw material of dispensing granules， and the powder properties have an important influence on subsequent molding process and product quality. As a new form of TCM， dispensing granules have been included in the management category of TCM decoction pieces， indicating a broader application market， and a consensus has also been reached on the importance of TCM powder research. Based on this， the author summarized the application progress of spray drying in the study of TCM powders， including the factors affecting spray drying process， such as liquid properties， process parameters and equipment factors， as well as the application of computational fluid dynamics （CFD） and thermodynamic model in spray drying process simulation. Moreover， some commonly used pharmaceutical excipients for the modification of TCM powders were also introduced such as maltodextrin， microcrystalline cellulose and povidone. In addition， spray drying technology can also be used as a preparation technology for new drug delivery systems such as microcapsules and solid dispersions. Through the summary of this paper， the author suggests that the future research direction of spray drying of TCM can be carried out from the aspects of application rule of the coprocessing auxiliary materials based on the "unification of medicines and excipients"， the "structure-property" relationship of spray-dried powders and the application of computer simulation and design， so as to further enrich the application of spray drying in the field of TCM powders.

Material Attribute Research in Quality Control of Traditional Chinese Medicine Pills： A Review / 中国实验方剂学杂志

As intelligent production of traditional Chinese medicine （TCM） has been inevitable， informatization and automation of the production process have become the precondition for realizing intelligent manufacturing of TCM， of which the accumulation of critical material attribute and the critical quality attribute are the basis. The study of material properties is of great significance to achieve the quality control of the final product in the process， but there is a lack of systematic induction and summary of the research on the attribute of TCM pills. Therefore， the authors analyzed and summarized the attributes of raw materials， excipients and intermediates in the pill unit process according to the classification of powder properties， rheological properties and texture properties. What’s more， the impact of material attributes on the quality of the final product was summarized. Besides， this review summarized the attribute characterization techniques involved in the pill process and provided some suggestions for the characterization of product quality attributes. Finally， based on the concept of quality by design （QbD）， the authors proposed that the study of material attribute should be combined with process analytical technology （PAT）， and the focus of drug quality control should be moved forward to guide equipment upgrading， so as to realize intelligent continuous manufacturing of TCM pills.

Establishment of Feedforward Control Model for Dry Granulation of Polysaccharide Components Based on Quality by Design / 中国实验方剂学杂志

ObjectiveA feedforward control model for dry granulation of polysaccharide components was established to guide the adjustment and optimization of critical process parameters （CPPs） in the design space， so as to reduce the impact of fluctuations in raw materials properties on the quality of medicines. MethodTaking Astragali Radix extract powder as the model drug， the design space of dry granulation CPPs was determined by Box-Behnken design. Astragali Radix mixed powder with different powder properties were prepared by mixture design， the variance inflation factor （VIF） was used to diagnose the multicollinearity of the powder properties， and principal component analysis （PCA） was used to extract the characteristic data of the model. Radial basis function neural network （RBFNN） was used to establish a feedforward control model for reflecting the relationship between the powder properties of polysaccharide components， dry granulation CPPs and one-time molding rate. ResultThe design space for dry granulation CPPs of polysaccharide components was 16-35 Hz for feeding speed， 10-23 Hz for roller speed， and 10-46 kg·cm-2 for roller pressure. The established RBFNN feedforward control model had a good predictive effect on the one-time molding rate of dry granulation of polysaccharide components， which could be used to guide the adjustment and optimization of CPPs in the design space， the relative error was 0.38%-6.73%， and the average relative error was 3.42%. ConclusionThe established feedforward control model can well reflect the relationship between the powder properties of the polysaccharide components， the dry granulation CPPs and the one-time molding rate of the granules， which can be used to guide the adjustment and optimization of CPPs in the design space， reduce the impact of material property fluctuation on product quality， and provide ideas for promoting the quality of traditional Chinese medicine from passive control to active control.

Current approaches of nanomedicines in the market and various stage of clinical translation

Compared with traditional drug therapy, nanomedicines exhibit intriguing biological features to increase therapeutic efficiency, reduce toxicity and achieve targeting delivery. This review provides a snapshot of nanomedicines that have been currently launched or in the clinical trials, which manifests a diversified trend in carrier types, applied indications and mechanisms of action. From the perspective of indications, this article presents an overview of the applications of nanomedicines involving the prevention, diagnosis and treatment of various diseases, which include cancer, infections, blood disorders, cardiovascular diseases, immuno-associated diseases and nervous system diseases, etc. Moreover, the review provides some considerations and perspectives in the research and development of nanomedicines to facilitate their translations in clinic.

Research on feedforward control method of mixing process for compound Danshen Dripping Pills based on quality by design(QbD) / 中国中药杂志

The mixing process is one of the key operation units for solid preparation of traditional Chinese medicine. The physical properties such as particle size, density and viscosity of the mixture are key factors that need to be controlled, which will directly affect the performance of the preparation molding process and product quality. Subsequent dripping process performance and appearance qua-lity of dripping pills will be affected by dynamic viscosity of materials in the mixing process. Based on this, with mixing process of compound Danshen dripping pills as the object, a feedforward control method for the dripping pill mixing process was established based on the concept of quality by design(QbD). Firstly, critical quality attribute(CQA)-dynamic viscosity, critical material attributes(CMAs)-the moisture content of compound Danshen extract, average molecular weight of polyethylene glycol 6000 and critical process parameter(CPP)-mixing temperature were identified through the analysis of properties for multiple batches of the raw materials and excipients as well as technological mechanism. Then the Box-Behnken experimental design was used to establish the regression model among CMA, CPP and CMA(R■=0.972 0, RMSE =16.24) to obtain the design space. Finally, through the verification of three batches within the design space, the mixing process temperature was adjusted according to the properties of the raw materials and exci-pients to achieve accurate control of the dynamic viscosity attribute. The relative deviation between the actual dynamic viscosity value and the target value was less than 3.0 %. The feedforward control of the mixing process of compound Danshen dripping pills was rea-lized in this study, which can contribute to improving quality consistency of the mixing process intermediates, simultaneously provide a reference for the research on the process quality control of other Chinese medicine dripping pills.

Optimization of Inclusion Technology of Volatile Oil from Ganmao Qingre Granules / 中国药房

OBJECTIVE：To optimize the inclusion technology of volatile oil from Ganmao qingre granules. METHODS ： Guided by the concept of “quality by design ”，taking volatile oil inclusion rate and inclusion complex yield as key quality attribute，comprehensive score of above two indexes after weighting as response value ，inclusion temperature ，inclusion time ，the ratio of β-CD to volatile oil as key technology parameters ，Box-Burman response surface design was adopted to establish the design space of key technology parameters and key quality attributes. The design space was optimized and verified by 95％ confidence interval. The stability of inclusion complex was investigated preliminarily. RESULTS ：The optimal design space ，i. e. the optimal technology parameters rang ，included inclusion temperature 35-40 ℃，inclusion time 1.8-2.0 h，the ratio of β-CD to volatile oil 9.5∶1- 10∶1（g/mL）. The results of 3 validation tests showed that the volatile oil inclusion rates were all over 62％，the yields of inclusion complex were all over 75％，and the comprehensive scores were all over 80 point. The results of preliminary stability showed that the inclusion rate of volatile oil ，the yield of inclusion complex and the comprehensive score did not change significantly. The difference in evaluation indicators within 7 days was within 5％. CONCLUSIONS ：The optimized inclusion technology is feasible ， and the obtained inclusion complex is stable.

A strategy for population pharmaceutical quality assessment based on quality by design / 药物分析学报

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 distri-bution,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 demon-strated 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.

Material manufacturability classification in high shear wet granulation process of Chinese medicine / 中国中药杂志

The high shear wet granulation(HSWG) process of Chinese medicine has a complicated mechanism. There are many influencing factors that contribute to this process. In order to summarize the manufacturability of different kinds of materials in HSWG, this paper constructed a material library composed of 11 materials, including 4 Chinese medicine extracts and 7 pharmaceutical excipients. Each material was described by 22 physical parameters. Several binders were employed, and their density, viscosity and surface tension were characterized. Combining empirical constraints and the principle of randomization, 21 designed experiments and 8 verification experiments were arranged. The partial least squares(PLS) algorithm was used to establish a process model in prediction of the median granule size based on properties of raw materials and binders, and process parameters. The surface tension and density of binders, as well as the maximum pore saturation were identified as key variables. In the latent variable space of the HSWG process model, all materials could be divided into three categories, namely the Chinese medicine extracts, the diluents and the disintegrants. The granulation of Chinese medicine extracts required low viscosity and low amount of binder, and the resulted granule sizes were small. The diluent powders occupied a large physical space, and could be made into granules with different granule sizes by adjusting the properties of binders. The disintegrants tended to be made into large granules under the condition of aqueous binder. The combination use of material database and multivariate modeling method is conducive to innovate the knowledge discovery of the wet granulation process of Chinese medicine, and provides a basis for the formulation and process design based on material attributes.

Analytical Qbd Approach For Development And Validation Of Rp-High Performance Liquid Chromatography Method For Determination Of Tofisopam In Pure Form And Tablets

A novel, simple, optimized reversed-phase chromatography method for assay of Tofisopam in pure and tablet form is developed. The experimental trial was by Box Behnken design using the Design Expert® software 10 version. The attributes selected were peak symmetry, number of theoretical, and peak purity. The predicted data satisfied with actual experimental data. The optimized chromatographic conditions required a quaternary pump with a mobile phase of Water: Acetonitrile 25:75 v/v at 1 mL/min, oven temperature at 25oC at 310 nm using C18(250 × 4.6 mm Id, 5μm) column and PDA detector with a run time of 5 min. The method was validated for linearity, precision, accuracy, and specificity. The method produced a linear response over a concentration range of 4–24 ppm with an overall average accuracy of 99.98%. The method was robust, reproducible, and specific with respect to the retention time of tofisopam.

Critical pharmaceutical process identification considering chemical composition, biological activity, and batch-to-batch consistency: A case study of notoginseng total saponins / 中草药·英文版

Objective: Critical pharmaceutical process identification (CPPI) is an important step in the implementation of quality by design concept to traditional Chinese medicines (TCMs). Risk assessment methods are usually used in CPPI. However, risk evaluation is usually subjective. The purpose of this work is to present a more objective CPPI method. Methods: A CPPI method considering chemical composition, biological activity, and batch-to-batch consistency was presented in this work. The manufacturing process of notoginseng total saponins (NTS) was investigated as an example. The changes of chemical composition, biological activity, and chemical composition consistency after main processes were measured and compared. A significant change of them indicated a critical process. Results: After extraction process and chromatography process, saponin purity and chemical composition similarity remarkably increased, and saponin content variations decreased. Thrombin inhibitory activity was remarkably decreased after chromatography process. Because of the large influences on NTS quality, extraction process and chromatography process were identified to be critical processes of NTS. Conclusion: Based on a comprehensive and objective examination of the role of each process, critical pharmaceutical processes can be identified. A similar method can also be applied to other TCM processes.

Quality control of ethanol extraction process of Corydalis Rhizoma based on quality by design (QbD) / 中草药

Objective: To improve the quality control level of ethanol extraction process of Corydalis Rhizoma (CR) by using quality by design (QbD), so as to meet the extraction requirements of Kedaling Tablets. Methods: The critical process parameters were solvent multiple, extraction time and soaking time, and the critical quality attributes were dry extract rate, content and transfer rate of dehydrocorydaline. The response surface methodology was used to establish the mathematical model between the critical process parameters and the critical quality attributes. The overlapping design space of multiple index design spaces was established to select the optimal operation space, where the process verification was carried out. Results: The operating space parameters of ethanol extraction of CR was 14-24 h of the immersion time, 3.0-4.0 times of the first time solvent multiple, 1.5-2.0 times of the second and third time solvent multiple, and 1.5-2.5 h of the extraction time. Under this operating space, the extraction yield of CR was ranged from 6%-8%, the content of dehydrocorydaline was more than 2.8%, and the transfer rate was not less than 85%. Conclusion: The concept of QbD is helpful to improve the ethanol extraction process of CR, and to obtain a reliable and suitable extraction operation space for the production of Kedaling Tablets.

Recent research progress in key technologies of Chinese materia medica manufacturing process quality control / 中草药

The development of Chinese materia medica (CMM) has risen to the level of national strategy. Under the new situation that the pharmaceutical industry implements the "Made in China 2025" strategy, quality control of the production process of CMM is one of the key areas in which the CMM industry needs to accelerate its breakthrough. The key common issues in process design, analysis and detection, process modeling, and manufacturing equipment and other aspects in the field of quality control of CMM production processes was analyzed in the paper. The progress in the three aspects of process understanding, real-time analysis method development and process control strategy establishment in the quality control system of CMM production process was reviewed. Combined with the author's corporate research practices, this paper introduces the application progress of key technologies such as quality by design (QbD), process analytical technology (PAT), experimental design (DOE), and multivariate statistical analysis in the above three research directions, and analyzes the difficulties problems in practical industrial application. The application prospect is prospected. The purpose of this article is to provide reference for CMM enterprises to apply and improve the quality control technology in the production process.

Multi-index optimization of alcohol extraction and water precipitation processes of Shenmai Injection based on quality by design concept / 中草药

Objective: The alcohol extraction and water precipitation processes of Shenmai Injection were optimized based on quality by design (QbD) concept and satisfaction algorithm. Methods: Hazard and operational analysis method was applied to conduct risk assessment of various process parameters in alcohol extraction and water precipitation processes of Shenmai Injection. Ethanol concentration, extraction time and alcohol-material ratio were selected as the critical process parameters of alcohol extraction, and the material pH, temperature and time were selected as the critical process parameters of water precipitation. A multiple linear regression model of critical process parameters and critical quality attributes were established by using Box-Behnken design. A design space was delineated according to the level of each index. Finally, the optimum operating condition was determined by the multi-index optimization algorithm. Results: Within the scope of the design space, when the alcohol concentration was 89.0%, the extraction time was 110 min, the alcohol-material ratio was 2.99, the desirability function of alcohol extraction of 0.722 was the best. When the material pH was about 4, the time was 40 h, the temperature was 2.0 ℃, the desirability function of water precipitation of 0.995 was the best. When the material pH was about 5, the time was 35 h, the temperature was 2.0 ℃, the desirability function of water precipitation of 0.999 was the best. Conclusion: The optimal conditions were determined based on QbD and satisfaction algorithm were conducive to ensuring the product quality and reducing the cost of production. This study has reference value for the guidance of pharmaceutical process research and actual industrial production.

Development of preparation process of icaritin-coix seed oil microemulsion based on quality by design concept / 中国中药杂志

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.