ABSTRACT
In recent years, continuous manufacturing technology has attracted considerable attention in the pharmaceutical industry. This technology is highly sought after for its significant advantages in cost reduction, increased efficiency, and improved productivity, making it a growing trend in the future of the pharmaceutical industry. Compared to traditional batch production methods, continuous manufacturing technology features real-time control and environmentally friendly intelligence, enabling pharmaceutical companies to produce drugs more efficiently. However, the adoption of continuous manufacturing technology has been slow in the field of traditional Chinese medicine(TCM) pharmaceuticals. On the one hand, there is insufficient research on continuous manufacturing equipment and technology that align with the characteristics of TCM preparations. On the other hand, the scarcity of talent with diverse expertise hampers its development. Therefore, in order to promote the modernization and upgrading of the TCM pharmaceutical industry, this article combined the current development status of the TCM industry to outline the development status and regulatory requirements of continuous manufacturing technology. At the same time, it analyzed the problems with existing TCM manufacturing models and explored the prospects and challenges of applying continuous manufacturing technology in the field of TCM pharmaceuticals. The analysis focused on continuous manufacturing control strategies, technical tools, and pharmaceutical equipment, aiming to provide targeted recommendations to drive the development of the TCM pharmaceutical industry.
Subject(s)
Medicine, Chinese Traditional , Quality Control , Drug Industry , Technology, Pharmaceutical/methods , Drugs, Chinese Herbal , Pharmaceutical PreparationsABSTRACT
Objective:To extract essential oil of Zanthoxyli Pericarpium， to prepare Zanthoxyli Pericarpium essential oil solid preparation and investigate its anti-fungal effect， in order to provide safe， green and efficient fungicide for the storage of Chinese herbal medicine and food. Method:The essential oil of Zanthoxyli Pericarpium was extracted by steam distillation method， gas chromatography-mass spectrometry （GC-MS） was adopted to analyze the chemical compositions and their relative contents in essential oil of Zanthoxyli Pericarpium from different producing areas， Agilent HP-5 capillary column was used for separation at programmed temperature （the initial temperature was 60 ℃， kept for 2 min， then increased to 280 ℃ by 10 ℃·min<sup>-1</sup>， kept for 5 min）， the scanning range was <italic>m</italic>/<italic>z</italic> 35-590. Zanthoxyli Pericarpium essential oil solid preparation was prepared by nanomolecular sieve adsorption method， and its inhibitory effect on <italic>Aspergillus flavus</italic> and its conidia was investigated. Ultra-high performance liquid chromatography-fluorescence detector （UPLC-FLD） was used to analyze the inhibitory effect of Zanthoxyli Pericarpium essential oil solid preparation on aflatoxin under the conditions of excitation wavelength of 360 nm and emission wavelength of 440 nm. Result:The average extraction rate of essential oil in Zanthoxyli Pericarpium from four producing areas was 5.2%. （+）-Limonene， linalool and linalyl acetate were the main components of Zanthoxyli Pericarpium<italic> </italic>essential oil<italic> </italic>from different producing areas. When the volume fraction of essential oil in the solid preparation was 0.1%， the inhibition rate of the solid preparation on the conidia of <italic>A</italic>. <italic>flavus</italic> was （16.41±8.89）%. When the volume fraction of essential oil in the solid preparation was 0.2%， the inhibition rate for the growth of <italic>A</italic>. <italic>flavus</italic> was （8.11±2.70）%. When the volume fraction of essential oil in the solid preparation was 0.5%， the inhibition rate for the growth of <italic>A</italic>. <italic>flavus </italic>was （21.62±5.41）%， the inhibition rate for <italic>A</italic>. <italic>flavus</italic> conidia was （45.43±5.67）%， and the inhibition effect for the aflatoxin could reach （90.47±12.77）%. Conclusion:There are some differences in the chemical composition of essential oil of Zanthoxyli Pericarpium from different producing areas. Zanthoxyli Pericarpium<italic> </italic>essential oil has a certain inhibitory effect on the formation of <italic>A. flavus</italic> conidia and the production of aflatoxin B<sub>1</sub>. It shows that Zanthoxyli Pericarpium essential oil can be developed into bacteriostatic preparation and used in the storage of Chinese medicinal materials and food.
ABSTRACT
3D printing technology has the advantages of accurate spatial distribution, accurate drug release and personalized drug dosage, which can make up for the shortcomings of traditional pharmaceutical technology. In recent years drop-on powder (DoP) 3D printing technology has been widely used in pharmaceutical preparation. Compared with other types of 3D printing technology, it is more simple, flexible and easy to operate. In 2015, Aprecia Pharmaceuticals announced that the US Food and Drug Administration (FDA) approves the launch of its first instant tablet Spritam® (levetiracetam) made with DoP 3D printing. After the first 3D printed medicine was launched, people also saw the unique advantages and broad prospects of DoP 3D printing technology platform in pharmaceutical preparation. This review focuses on the technical principles and key factors of DoP 3D printing, its application in the preparation field and its future development challenges.
ABSTRACT
OBJECTIVE:To provide reference for improving the homogeneity and stability of domestic cefetamet pivoxil hydro-chloride oral solid preparation and its control standrads. METHODS:105 batches of cefetamet pivoxil hydrochloride preparations (tablets,granules,dry suspensions and dispersible tablets)were tested by statutory inspection test in respects of property,identifi-cation,weight difference or load difference,moisture,microbiological limits,related substances,dissolution degree and content, etc.,and results were analyzed. Exploratory research was conducted for its impurity sources,dissolution consistency evaluation, the correlation between the remaining validity period with relative substance and content,etc. RESULTS:Statutory tests showed, 103 batches were qualified in the 105 batches of samples(98.1%). The unqualified items were property and related substances,the other items met relevant regulations. Besides,the determination method for related substances in dispersed tablets was quite differ-ent with other preparations. Results of exploratory research showed the related substances in preparations originated from raw materi-als,degradation reaction in manufacturing or storage. Compared with domestic reference tablets and granules,f2 of dissolution of other products were mostly less than 50;there was no correlation in related substances,content with the remaining validity period. CONCLUSIONS:The 105 batches of domestic oral solid preparation of cefetamet pivoxil hydrochloride are basically qualified;cur-rent standard is basically feasible for tablets,granules and dry suspensions,while the standard for dispersible tablets needed to be improved immediately.
ABSTRACT
Objective: To analyze and estimate the risks of failure modes in a pharmaceutical Co.Ltd.in Nanjing producing solid preparations by collinear production, and come up with measurements to improve the quality level accordingly.Methods: The quality risk level evaluation table for the failure modes in the various steps of collinear production was obtained through the failure mode and effects analysis (FMEA).The risk control measurements were put forward in order to control and improve different failure modes with various unacceptable risk levels.Results: The risks of solid preparations by collinear production were greatly reduced through FMEA.Conclusion: The FMEA method is an effective way to improve the quality level of collinear products.Meanwhile, there are limitations of FMEA, and other risk management methods should be combined to control the overall risk of drug production.Moreover, the failure modes at the same risk level with different properties should be analyzed and controlled accordingly.The above methods can improve the risk management level of a company and reduce the risks of cross-contamination, mistakes and air-transferring in order to enhance the efficiency of quality management system and produce safe and effective drugs.
ABSTRACT
Objective:To explore the chemical and biological assay pattern for the quality control and evaluation of Chinese mate-ria medica solid preparations ( CMMSP) . Methods:Compound berberine tablets were used as the model drug, the inhibition against sensitive strains of the dissolution solution at different time points was studied with water as the dissolution medium, and the cumulative dissolution of compound berberine tablets was obtained based on the bacterial inhibitory rate. The dissolution of hydrochloric acid ber-berine was also determined by HPLC, and a f2 similar factor method was used to evaluate the relevance of the two methods. Results:The antimicrobial test showed that berberine was sensitive to escherichia coli,staphylococcus aureus, bacillus subtilis, micrococcus luteus and candida albicans etc, and among them, the antibacterial circle edge of bacillus subtilis was clear with higher sensitivity. The disso-lution curve of compound berberine tablets determined by HPLC as the reference, the similarity factor f2 of bio-dissolution curve of com-pound berberine tablets from 7 different manufactures was greater than 50, which suggested that the dissolution determination method based on biological titer determination could comprehensively reflect the bioavailability of compound berberine tablets. Conclusion:The biological activity evaluation method for dissolution is expected to be one of the effective means for in vitro dissolution test of CMMSP.
ABSTRACT
OBJECTIVE: To develop an analytical method for determination of unknown residual solvents in solid drug products by GC-MS in order to meet the need of supervision. METHODS: Fifty residual solvents including benzene, carbontetrachloride, 1, 2-di-chloroethane, 1, 1, 1-trichloroethane, acelonitrile, chlorobenzene, acetone, etc, were determined by GC/MS using selected ion monitoring (SIM) mode. RESULTS: Good linearity was obtained with correlation coefficients of more than 0.9975 for all the solvents. The average recoveries of the quality control samples at low, middle and high concentrations were from 88.8% to 109.8% and the relative standard deviations (RSDs) were lower than 11.6%. The limits of detection (TODs) were in the range of 0.00003-0.3μg·mL-1, while the limits of quantitation (LOQs) were in the range of 0.00009-1 μg ·mL-1. CONCLUSION: The method is simple, rapid, sensitive and accurate, and can be used for the simultaneous determination of 50 residual solvents in solid preparations such as tablets and capsules.
ABSTRACT
Objective: To explore the effects of different pulverization fineness of solid preparations of Chinese materia medica on their in vitro dissolution, using MTT method combined with HPLC. Methods: Compound Biejia Ruangan Tablet (CBRT) was used as model drug, and MTT method was used to obtain the characteristic cell inhibitory rate by different pulverization fineness of dissolving solutions in the dissolution medium (phosphate buffer, pH value 7.4) at different time points. From these results, the cumulative dissolution of CBRT based on cell inhibitory rate was obtained. The dissolution rates of paeoniflorin was determined by HPLC method. Using f2 similar factor, the relevance of these two methods was evaluated. Results: Dissolution of paeoniflorin is changed with the change of pulverization fineness, the accumulative dissolutions of 200 and 300 meshes in vitro were higher than those of other meshes. The results showed that f2 values of 200 and 300 meshes were more than 50, indicating that there was a good correlation between the two methods of measuring the dissolution rate. Conclusion: The results show that the biological potency detection could be used to screen the particle size of CBRT. Considering the production cost of CBRT, 200 mesh is the best particle size.
ABSTRACT
AIM:To compare the dissolution in vitro between Beimu Pills(Bulbus fritillariae cirrhosae,Radix et Rhizoma glycyrrhizae,Semen armeniacae amarum) and Beixinggan Buccal Tablet(70% alcohol percolate of Bulbus fritillariae cirrhosae;extract of Radix et Rhizoma glycyrrhizae and extract of semen armeniacae amarum) to evaluate the reform of the traditional solid preparation.METHODS:Verticine and verticinone were adopted as the reference substance for the calculation of cumulative dissolution percentage.RESULTS:Cumulative dissolution reached 95% of dissolution rate,it took 60 min for Beixinggan Buccal Tablet and it took 180 min for Beimu Pills at the same condition.CONCLUSION:Dissolution method applied to the control over TCM preparation quality and to the reform of preparation can be recognized as one of the quality standard.