Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

During the decocting process of traditional Chinese medicine(TCM), molecules spontaneously form self-assembled nanoparticles(SAN) through intermolecular non-covalent interactions. This process effectively addresses the low bioavailability of poorly soluble components, becoming a research hotspot. However, SAN formed in traditional decoctions often exhibit low Zeta potential, poor stability, and easy aggregation, which limit their clinical applications. According to the extensive studies of SAN in TCM decoctions, this paper proposes innovative strategies of utilizing techniques such as micro-precipitation and pH-driven methods to improve SAN. These strategies significantly enhance the uniformity and stability of SAN and effectively increase the transfer rate of poorly soluble components, overcoming the technical bottlenecks of low stability and drug delivery efficiency in TCM decoctions. This article reviews the origins, advantages, and limitations of traditional SAN, discusses the strategies for improving SAN construction and characterization, and delves into the scientific issues that need to be addressed in future research. The aim is to provide new directions for the development of modern TCM preparations.
Nanoparticles/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional ; Drug Delivery Systems ; Animals ; Drug Compounding/methods*

"Drug-drug co-processing"(DDCP) is a distinctive technique in the field of traditional Chinese medicine(TCM) processing. By synergistically processing target materials with specific drugs or medicinal juices, it demonstrates significant advantages in toxicity reduction, efficacy enhancement, and the modulation of medicinal properties. This study systematically reviews the historical evolution of DDCP and innovatively constructs a tripartite technical classification framework encompassing dry drug processing, medicinal juice processing, and fractional processing. The study finds that dry drug processing includes techniques such as stir-frying, roasting, steaming, and boiling; medicinal juice processing comprises ten core techniques including immersion, stir-frying, and steaming; while fractional processing adopts a novel method of differentially processing equal portions, showing unique advantages in the treatment of medicinal materials such as Atractylodis Rhizoma and Atractylodis Macrocephalae Rhizoma. Theoretical analysis indicates that this technique, through multi-component synergistic mechanisms, not only effectively moderates medicinal properties and enhances therapeutic efficacy but also facilitates the development of novel drugs, significantly expanding the scope of medicinal applications. This study provides the first systematic elucidation of the processing mechanisms underlying DDCP, offering theoretical support for the modernization of traditional processing techniques and bearing important practical significance for preserving the cultural wisdom of TCM and promoting innovation in processing technologies.
Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional/methods* ; Drug Compounding/methods*

Nano-drug delivery systems offer significant benefits, including high specific surface area, structural and functional diversity, and surface modifiability. When formulated as inhalable nano-formulation, these can not only enable precise pulmonary drug delivery but also improve pulmonary bioavailability and enhance thera-peutic efficacy. Currently, there are four types of inhalable nano-formulations for the treatment of respiratory diseases. Inhalable liquid preparations exhibit facile manufactur-ability and broad applicability yet demonstrate compromised stability during aerosolization. Through structure optimization, surface modification, dispersion medium optimization and device improvement, the atomization stability of nano-drug has been enhanced. Pressurized metered-dose inhalers loaded with nano-drugs face technical challenges: conventional propellants may dissolve nano-carriers, whereas co-solvents like ethanol compromise delivery efficiency. Thus, it is necessary to develop novel propellants that provide thermodynamic stability and optimal delivery performance. Nano-drug formulations in dry powder inhalers exhibit relatively favorable physical stability, however, pulmonary delivery efficiency and nanoparticles integrity during processing remain problematic. Pulmonary delivery efficiency can be improved by employing strategies such as blending excipients to promote the re-dispersibility of nanoparticle agglomerates, optimizing the design of microcarrier, and innovating preparation processes. In contrast, soft mist inhalers are an ideal option for pulmonary delivery of nano-drugs owing to their gentle and efficient atomization properties to maintain nano-drug integrity. This review summarizes the inhalable nano-formulations and focuses on challenges and proposed strategies encoun-tered in integrating nano-drug delivery systems and inhalation drug delivery systems. It aims to provide references for the future development of inhalable nano-formulations.
Administration, Inhalation ; Humans ; Drug Delivery Systems/methods* ; Nanoparticles ; Dry Powder Inhalers ; Nanoparticle Drug Delivery System ; Drug Compounding ; Metered Dose Inhalers ; Drug Carriers

We have isolated an intestinal probiotic strain, Pediococcus acidilactici HRQ-1. To improve its gastrointestinal fluid tolerance, transportation and storage stability, and slow-release properties, we employed the extrusion method to prepare the microcapsules with P. acidilactici HRQ-1 as the core material and sodium alginate and chitosan as the wall material. The optimal conditions for preparing the microcapsules were determined by single factor and orthogonal tests, and the optimal ratio was determined by taking the embedding rate, survival rate, storage stability, gastrointestinal fluid tolerance, and release rate as the evaluation indexes. The results showed that under the optimal embedding conditions, the embedding rate reached (89.60±0.02)%. Under the optimal formula of freeze-drying protective agent, the freeze-drying survival rate reached (76.42±0.13)%, and the average size of the microcapsules produced was (1.16±0.03) mm. The continuous gastrointestinal fluid simulation experiments confirmed that the microcapsules ensured the viable bacterial count and can slowly release bacteria in the intestinal fluid. The curve of the viable bacterial count during storage at 4 ℃ and room temperature indicated that the prepared microcapsules achieved strains' live number protection. The formula and preparation process of P. acidilactici microcapsules may provide a technological reserve for the preparation of more live bacterial drugs in the future.
Pediococcus acidilactici/chemistry* ; Probiotics/chemistry* ; Capsules/chemistry* ; Alginates/chemistry* ; Chitosan/chemistry* ; Drug Compounding/methods* ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry* ; Freeze Drying

"Solid-liquid excipients" co-production is one of the typical processing methods of excipients used from ancient times to the present day, and is widely applied in various processing schools and regional specialty varieties. This method significantly reduces the toxicity of traditional Chinese medicine(TCM), moderates medicinal properties, and enhances clinical efficacy. However, modern scientific research has given it limited attention, and many co-production methods of "solid-liquid excipients" have not been applied in production and practice. This paper reviewed the historical development of "solid-liquid excipients" co-production, outlined modern processing standards and methods in different processing schools, and further elaborated on the purposes and effects of this co-production method. This study is expected to provide references and evidence for further in-depth research, inheritance, innovation, and practical application.
Chemistry, Pharmaceutical/history* ; Drug Compounding/methods* ; Drugs, Chinese Herbal/chemistry* ; Excipients/chemistry* ; History, 20th Century ; History, 21st Century ; History, Ancient ; Medicine, Chinese Traditional/history*

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.
Calorimetry, Differential Scanning ; Desiccation ; Drug Compounding/methods* ; Drug Stability ; Silybin ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Technology ; X-Ray Diffraction

Extrusion-spheronisation method was used to prepare Rhus chinensis total phenolic acid pellets. The formula and preparation of R. chinensis total phenolic acid pellets were optimized. The formulas( drug loading capacity,diluent,wetting agent and anti-sticking agent) were determined by the single factor test with yield,appearance and performance as the indexes. The preparation was optimized by Box-Behnken design and response surface method,with the rate of extrusion,rate of spheronization and time of spheronization as the independent variables and the overall desirability value of yield,friability and roundness as the dependent variables. The optimal formula of pellets was as follows: drug loading capacity 28. 7%,MCC-lactose 9 ∶1,silicon dioxide as anti-sticking agent,and 60% ethanol as wetting agent. The optimal preparation was determined as follows: the rate of extrusion was 43 r·min-1,the rate of spheronization was 1 800 r·min-1,and the time of spheronization was 4 min. The absolute deviation between predicted value and estimated value under the conditions was less than 5. 0%,with a high degree of model fit. The preparation parameters obtained were accurate,reliable and reproducible. Under scanning electron microscopy( SEM),R. chinensis total phenolic acid pellets were uniform in diameter,round and smooth. The optimal formulation and process are stable and feasible for preparing R. chinensis total phenolic acid pellets.
Drug Compounding ; methods ; Hydroxybenzoates ; chemistry ; Particle Size ; Rhus ; chemistry ; Solubility

Aconitums,represented by Aconite Radix,Aconiti Lateralis Radix Praeparata and Aconiti Kusnezoffh Folium,is a kind of traditional Chinese medicine with a long medicinal history in China. They possess the significant toxicity and therapeutic effects simultaneously. Their potent effects of rescuing from dying,curing rheumatism,anti-inflammation,and analgesia make Aconitums highly regarded by physicians and pharmacists of various dynasties. However,countless poisoning cases caused by an irrational use of Aconitums were reported. In case of improper application and exceeding the therapeutic window,the acute cardiotoxicity and neurotoxicity would be caused,seriously threatening health and even life of the users. Therefore,the clinical application of Aconitums is limited to some extent. To avoid its toxicity and ensure the safety of medicinal use,Aconitums is usually used in a form of its processed products instead of the crude herbs,or combined with some other traditional Chinese medicines in a normal prescription. A proper processing and compatibility method can detoxicate its severe toxicity,reduce the adverse reactions,and also significantly broaden the indications and application range of Aconitums. This provides a guarantee for the secondary exploitation and utilization of Aconitums. In this paper,the traditional processing methods of Aconitums,along with the modern advancement were reviewed,and the mechanisms of detoxification by processing and compatibility were also illuminated. The physical detoxification mode and chemical detoxification mode were found as two main detoxification ways for Aconitums. In particular,the detoxification by hydrolysis,ion-pair,and saponification were three main means. The mechanisms illustrated in this paper can be a reference to the development of modern processing method and a guidance for appropriate use of Aconitums in clinical application.
Aconitum ; chemistry ; toxicity ; China ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Medicine, Chinese Traditional ; Plant Leaves ; chemistry ; Plant Roots ; chemistry

β-Carotene is one of the most abundant natural pigments in foods; however, usage of β-carotene is limited because of its instability. Microencapsulation techniques are usually applied to protect microencapsulated β-carotene from oxidization. In this study, β-carotene was microencapsulated using different drying processes: spray-drying, spray freeze-drying, coating, and spray granulation. The properties of morphology, particle size, water content, thermal characteristic, and chemical stability have been explored and compared. Scanning electron microscopy measurements showed that the coated powder had a dense surface surrounded by starch and suggested that the coating process gave a microencapsulated powder with the smallest bulk density and the best compressibility among the prepared powders. The chemical stabilities of microcapsules were evaluated during six months of storage at different temperatures. The coated powder had the highest mass fraction of β-carotene, which indicated that the coating process was superior to the three other drying processes.
Drug Compounding/methods* ; Drug Stability ; Freeze Drying ; Microscopy, Electron, Scanning ; Technology, Pharmaceutical ; beta Carotene/chemistry*