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@#Most drugs taste bitter and irritating, resulting in poor compliance of patients, and the bad odor affects the therapeutic effect. The successful research and development of a drug should not only conform to the five quality characteristics of effectiveness, stability, safety, uniformity and economy, but also the compliance of patients to drugs with bad odor. The development of taste masking techniques is critical for bitter drugs.This review describes the principles, advantages and drawbacks of traditional taste masking techniques, and introduces the mechanism and application of novel taste masking techniques, such as melt granulation, hot melt extrusion, 3D printing, drug complex preparation, and bitter taste inhibitors. The in vitro evaluation methods of drug taste masking effect, such as functional magnetic resonance imaging, in vitro dissolution, and electronic tongue technology, are described. And introduce in vivo evaluation methods, such as animal and human taste, in the field of taste masking effect. A new strategy of BP neural network prediction model for drug taste evaluation is proposed, with a view to providing theoretical reference for the future research on drug taste masking.
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ObjectiveTo screen the preparation technology of Baoyuan chewable tablets and to preliminarily elucidate its anti-fatigue effect and mechanism. MethodTaking encapsulation rate of volatile oil， extract rate and extraction rate of active ingredients as indexes， single factor test and orthogonal test were used to optimize the volatile oil inclusion， aqueous decoction and formulation molding processes of Baoyuan chewable tablets. ICR rats were randomly divided into the blank group， model group， Gaoshan Hongjingtian oral liquids group（6.01 mL·kg-1） and and Baoyuan chewable tablets low， medium， and high dose groups（2.1， 4.2， 8.4 g·kg-1）， 8 mice in each group， and were administered by gastric gavage at the corresponding dose once a day， the blank and model groups were given equal volume of saline for 15 d. After the last administration for 30 min， the mice were loaded with 5% of the body mass of lead at the tail and swam until exhaustion to establish the fatigue model， and the weighted swimming time of the mice in each group was recorded， meanwhile， the muscle tissues of the mice were sliced， stained by hematoxylin-eosin（HE） and subjected to pathological observation， and the levels of blood urea nitrogen（BUN）， lactic acid（LA）， liver glycogen（LG）， activities of lactate dehydrogenase（LDH） and creatine kinase（CK） in the serum were determined. ResultThe optimal inclusion process of cinnamon oil in Baoyuan chewable tablets was 10∶1 for β-cyclodextrin-volatile oil， and inclusion at 50 ℃ for 2 h with saturated aqueous solution method. The optimal water extraction process was to extract twice， adding 10 times of water to extract for 50 min for the first time， and adding 9 times of water to extract for 40 min for the second time. The ratio of the extract of Baoyuan chewable tablets with microcrystalline cellulose， maltodextrin， mannitol， citric acid， magnesium stearate was 63∶13∶8∶17∶17∶1∶1， the tablets were pressed by wet granulation， the each tablet weight was 1.2 g， and the hardness was 60-80 N. Compared with the model group， Baoyuan chewable tablets low， medium， and high dose groups could significantly prolong the exhaustion time of mice in weight bearing swimming（P<0.05， P<0.01）， and improve the exercise endurance of the body， and the results of HE staining showed that all dose groups of Baoyuan chewable tablets could significantly improve the muscle tissue damage caused by exercise， significantly reduce the levels of BUN， LA and the activities of LDH and CK in serum（P<0.01）， and significantly increase the content of LG（P<0.05， P<0.01）. ConclusionThe optimized preparation process of Baoyuan chewable tablets is stable and feasible， and the preparation can improve exercise endurance by increasing the LG level in liver tissue， and relieve muscle soreness by accelerating the removal of LA from the body， and reduce CK and LDH activities to exert anti-fatigue effects.
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Personalized traditional Chinese medicine(TCM) granules are positioned as a solid dosage form of TCM decoctions, boasting strong applicability and wide application range. The market prospect of personalized TCM granules is promising in that their preparation by mixed decoction makes up for the shortcoming of formula granules like the Chinese patent medicine granules and classical TCM prescription granules whose components cannot be changed flexibly. However, such factors as insufficient basic research, equipment mismatch, and low process commonality have limited their clinical application. After analyzing the characteristics of perso-nalized TCM granules, their production status, and the bottlenecks restricting their development, this paper pointed out the meaning and key points of developing a generalized preparation process for personalized TCM granules and affirmed the vital roles of the preparation and process prediction system and the on-line detection technology in improving the productivity of granulation. Finally, some assumptions on technology development for solving the specific problems of personalized TCM granules were shared to provide some ideas for the application and development of personalized TCM granules in clinical practice.
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Drugs, Chinese Herbal , Medicine, Chinese Traditional , PrescriptionsABSTRACT
OBJECTIVE: To prepare Cinnamomi Ramulus standard decoction according to the traditional decoction method, and study the preparation process and quality control of Cinnamomi Ramulus formula granules. METHODS: The standard decoctions of 16 batches of Cinnamomi Ramulus were prepared using decocting pot. The extracting rate, contents and transfer rates of cinnamic acid and cinnamaldehyde were calculated. The preparation process of Cinnamomi Ramulus dispensing granules was improved based on the parameters of standard decoction. The volatile oil was collected while extracting, and the β-cyclodextrin inclusion technology was applied in the granulation process. Based on the parameters of standard decoction, the quality standard of Cinnamomi Ramulus formula granules was established. RESULTS: The extracting rate of Cinnamomi Ramulus standard decoction was 3.58%-6.10%; the cinnamic acid content was 0.99%-2.59% and the transfer rate was 39.56%-62.28%; while the cinnamaldehyde content was 1.95%-4.69% and the transfer rate was 4.76%-7.85%. According to the standard decoction, 1 g of Cinnamomi Ramulus formula granules was equivalent to 14 g of pieces, containing cinnamic acid (0.50%-1.43%) and cinnamaldehyde (0.98%-3.50%). Six characteristic peaks in specific spectra were confirmed, including protocatechuic acid (1), coumarin (2), cinnamic acid (3), 2-methoxycinnamic acid (4), cinnamaldehyde (5) and 2-methoxycinnamaldehyde (6). CONCLUSION: In this study, the quality parameters of Cinnamomi Ramulus standard decoction are determined by traditional decocting pot. The strategy of establishing the preparation process and quality standard of Cinnamomi Ramulus formula granules based on standard decoction is proposed. It can provide reference for the research of Cinnamomi Ramulus dispensing granules and other Chinese medicine preparations containing volatile oil.
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@#The high-purity impurity C was isolated and purified from a new anti-allergic drug, rupatifen, by nucleophilic substitution reaction with bromobutaric acid, and its structure was confirmed by IR, UV, MS, 1H NMR, 13C NMR, DEPT135°,HSQC, HMBC, and 1H-1HCOSY. The preparation process of impurity C in this study was simple and easy to obtain under mild conditions, with the purity of 99.0% and the yield of 25%-30%;and the sample met the target compound by structural confirmation. The preparation process and structure confirmation provided sufficient impurity C reference substance for impurity research of raw materials and preparations of rupatifen fumarate, which laid a solid foundation for quality research of new drugs.
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Objective: To prepare silymarin nanosuspension (SM-NS) with glycyrrhizic acid as stabilizer, and investigate the in vitro release characteristics and charge stabilization mechanism. Methods: SM-NS was prepared by high-speed shear-high pressure homogenization method. SM-NS lyophilized powder were prepared by freeze-drying method and characterized by physical and chemical characterization and in vitro release. The stability mechanism of SM-NS was studied from the ionic strength and pH value. Results: The dosage of glycyrrhizic acid (GA) was 0.15%. The preparation process was shear rate of 19 000 r/min, shear time of 4 min, homogenization pressure of 100 MPa, homogenization times of 12 times, and lyoprotectant was mannitol 3%, the average particle size of SM-NS lyophilized powder was (516.4 ± 10.4) nm, PDI was (0.260 ± 0.046); The in vitro release results showed that the dissolution rate and solubility of SM-NS lyophilized powder were significantly higher than the physical mixture; The study of charge stability mechanism showed that licorice acid can provide good charge stabilization and strong resistance to environmental impact. Conclusion: SM-NS is a potential and new nano-drug with high safety, which is formed by the charge stability of GA to significantly improve the solubility and stability of silymarin.
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Chuanxiong Chatiaosan was first recorded in Taiping Huimin Heji Jufang, which was made up of 8 herbs, including Chuanxiong Rhizoma, Menthae Haplocalycis Herba, Asari Radix et Rhizoma, Schizonepetae Herba, Saposhnikoviae Radix, Angelicae Dahuricae Radix, Notopterygii Rhizoma et Radix and Glycyrrhizae Radix et Rhizoma. This prescription mainly contains a variety of alkaloids, flavonoids, phenylpropanoids, volatile oils and other compounds, which play the biological activity of promoting blood circulation and relieving pain. Modern pharmacological studies have confirmed that Chuanxiong Chatiaosan can reduce blood viscosity, improve cerebral circulation, and has central analgesic effect to treat migraine effectively. However, the mechanism for treating migraine of this prescription is still unclear. The author elaborated the research status of Chuanxiong Chatiaosan from four aspects, including quality control method, chemical composition, preparation technology and pharmacological research, hoping to provide references for rational clinical application and explanation of pharmacological mechanism of this prescription.
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OBJECTIVE: To optimize the formulation and preparation process of fast-dissolving PVP microneedles, and provide a high-quality carrier for PVP drug-loaded microneedle research. METHODS: On the basis of single factor, the needle tips dissolution time and insertion ratio were used as the evaluation indexes, and the optimal preparation process of microneedle was optimized by Box-Behnken method. RESULTS: From the single factor test and the Box-Behnken test, it was known that the optimum preparation conditions were as follows: the needle tip concentration was 0.70 g•mL-1, the temperature was 40 ℃, and the humidity was 40%. The microneedle height was 600 μm, the width was 200 μm, the pitch was 500 μm, quadrangular pyramid. The area of the microneedle patch was 0.56 cm2, the dissolution time in water was (41.00±3.74)s, and the insertion ratio was (93.19±5.25)%. CONCLUSION: The PVP fast-dissolving microneedles can be prepared simply and conveniently by the Box-Behnken method, which provides a reference for the preparation of further drug-loaded microneedles.
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Objective: To prepare a new hesperidin nanoemulsion (HDN-NE) with glycyrrhizic acid as emulsifier, by which could develop a “new green nano-pharmaceutics” of hesperidin. Methods HDN-NE was prepared by high-speed shearing and high-pressure homogenization. The prescription of HDN-NE was optimized with particle size, PDI, and appearance as indexes. The physicochemical property and stability of HDN-NE prepared by the optimal prescription were studied. Results: The optimal prescription of HDN-NE was as follow: The content of hesperidin, glycyrrhizic acid, and oil phase were 0.1%, 0.3%, and 5%, respectively. The shear rate was 13 000 r/min, the cutting time was 2 min, the homogeneous pressure and times were 100 MPa and 6, severally. The result showed that the prepared HDN-NE had the mean size of (262.7 ± 3.1) nm, PDI of 0.234 ± 0.009, Zeta potential of (-35.42 ± 0.72) mV, and solubility of (460.3 ± 2.1) μg/mL. The physicochemical property study showed that the conductivity was (116.4 ± 1.7) μs/cm, the pH was 6.820 ± 0.008, and the turbidity was 451 cm-1 (n = 3). It was identified as O/W emulsion by dyeing method. The droplets were spherical and uniform by transmission electron microscopy. The stability study showed that HDN-NE had good stability. Conclusion: HDN-NE with glycyrrhizic acid as an emulsifier can significantly improve the solubility and stability of hesperidin, which is a new potential nano-drug with safety.
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Objective: To prepare substance benchmarks of Baihe Dihuang Decoction (BDD), and evaluate the scientificity and rationality of preparation process by analyzing the process quality. Methods: Fifteen batches of substance benchmarks were prepared according to the ancient method, the content of catalpol and acteoside in the preparation process was determined, and the transfer rate and extractum rate were calculated. Fingerprints of 15 batches of decoction pieces, decoction, concentrate and substance benchmarks were detected by HPLC, and the common peaks of fingerprints were attributed and identified; In addition, the similarity of fingerprints were evaluated. Results: In 15 batches of substance benchmarks, the transfer rates of catalpol and acteoside were 81.40%—92.88% and 28.90%—41.41% respectively, the extractum rate was 36.06%—41.71%, and without discrete data. During the process of decoction, concentration and freeze-drying, the transfer rates of effective components were stable. In the fingerprints of substance benchmarks, 16 common peaks were determined, of which six peaks belong to Lilii Bulbus, nine peaks belong to Rehmanniae Radix. Three peaks were identified. The similarity of fingerprints of decoction pieces, decoction, concentrate, and substance benchmarks were all over 0.9. The similarity of reference fingerprints of decoction, concentrate, and substance benchmarks were over 0.99. Conclusion: The fingerprint method is reasonable and feasible, which can be used for simultaneously determining the fingerprint of decoction pieces, intermediates and substance benchmarks. The preparation process is scientific and reasonable, and will not changes substance basis significantly. The paper establishes a foundation for the development of preparation of BDD, and provides a new idea for the evaluation of process and quality of the substance benchmarks of classical famous prescriptions.
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With the development of high and new technology, such as material chemistry and computer technology, the formulation process is also constantly innovating and improving. In recent years, 3D printing technology has become a research hotspot in the formulation industry. Different from traditional preparation methods, 3D printing technology can realize personalized production and solve storage problems of drugs. Because of its advantages of simple production, convenient carrying, low cost and strong patient compliance, it may change the design and production mode of drugs in the future and have good development prospects in the field of preparation. This paper reviews principles, the latest research progresses, advantages and challenges of 3D printing by searching CNKI, SCI, Springer databases and collating relevant literatures, and forecasts the development of 3D printing technology in the field of traditional Chinese medicine preparations, aiming to provide some references for the application of the technology in the traditional Chinese medicine preparation industry.
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Objective: To optimize the preparation process of Schisandrae Chinensis Fructus granules(SCFG) to obtain a stabilized and qualified SCFG-preparation. Methods: The Schisandrae Chinensis Fructus raw materials were extracted by decoction with water,and the extraction process was optimized by the orthogonal test. In the orthogonal test, the yield of total extract and the extraction rate of schizandrin were used as evaluation index,and the effect of solid-liquid ratio,decoction time and extraction times on the indexes were investigated to optimize the related parameters of these fac- tors. Meanwhile,the concentration process,drying process and granulation process were also investigated to finally opti- mize the preparation process of SCFG products. The content of schizandrin was determined by the HPLC method. Re- sults Under the HPLC conditions in the Pharmacopia of the People’s Republic of China(2015 edition),schizandrin showed a good linearity in the range of 0.03598-0.28784 μg(r=1.0000),with the average recovery rate 99.32% and RSD 2.17%. The conditions for the optimized extraction process were 3 times of extraction,with 0.5 h of each decoction time and with the 1:8,1:6 and 1:6 solid- liquid ratio in turn. The conditions for the optimized concentration process were concentrating at 60℃ and -0.08 MPa vacuum to a certain concentration. The conditions for the optimized drying pro- cess were drying at 60℃ and -0.09 MPa vacuum to a dryness. The conditions for the optimized granulation process were adding appropriate amount of dextrin,using 90% alcohol as moistening agent,and sifting with 14 mesh sieve and desic- cating at 60℃. Conclusion: The improved method is feasible,simple,stable and suitable for large-scale production of SCFG products.
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This paper compared and analyzed the relevant records of Chinese medicine pharmacy in the Han,Tang and Song dynasties,and summarized the changes of the dosage forms,preparation techniques and administration methods of Chinese medicine with the development of history.In this study,three classic medical works in the Han,Tang and Song dynasties,including Treatise on Febrile Diseases Caused by Cold,Valuable Prescriptions for Emergency and Formularies of the Bureau of People's Welfare Pharmacies,were taken as the research objects,and the development of the dosage forms,auxiliary materials,preparation technology and medication theory were summarized and explored by the ways of content analysis,comparative analysis and case analysis.The comparison showed that in the development process,the dosage forms gradually increased,but the liquid dosage forms gradually decreased,the solid dosage forms gradually increased.Not only the dosage forms varied in the number,types of excipients used more and more,but the level of preparation had been constantly improved while the methods of taking became more detailed.This evolution of dosage forms and pharmaceutical technologies in Chinese history is worth learning and thinking about it.Through exploring the traditional Chinese medicine(TCM) technologies and theories in the Han,Tang and Song dynasties,we can contribute to the inheritance of traditional preparations and it can provide the basis for the development of modern preparations with TCM characteristics.
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Objective:To compare the total daily doses of 16 active components in big honeyed pills, concentrated pills and tablets of Fuzi Lizhongwan. Method:Three dosage forms of Fuzi Lizhongwan were prepared according to the process described in the literature. RRLC-QqQ-MS was employed to analyze the contents of 16 active ingredients with mobile phase of 0.1%formic acid aqueous solution-0.1%formic acid acetonitrile solution for gradient elution,the separation was performed on a Accucore RP-MS column(2.1 mm×100 mm, 2.6 μm) with a flow rate of 0.3 mL·min-1 and the column temperature at 30℃, the mass spectrometry condition was electrospray ion source, positive and negative ion switching mode for detection, multi-reaction monitoring mode(MRM) for scanning. The contents of 16 active ingredients were calculated, and the normalization arithmetic method was used for comparing the total daily doses of these active ingredients in three dosage forms of Fuzi Lizhongwan. Result:Processed products of Aconiti Lateralis Radix Praeparata were used as raw powder in preparation process of the three dosage forms, so there was no significant difference in the contents of six alkaloids in the three dosage forms, while the contents of other 10 active ingredients from Zingiberis Rhizoma, Codonopsis Radix, Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle were significantly higher in big honeyed pills than those in concentrated pills or tablets(PConclusion:The total daily doses of 16 active ingredients in the three dosage forms of Fuzi Lizhongwan are significantly different caused by preparation process, prescription and dosage.
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OBJECTIVE: To establish the preparation technology of Moutan Cortex standard decoction and formula granules. METHODS: Moutan Cortex standard decoction was prepared by decocting pot and the parameters and fingerprints of 15 batches of decoction were established.To improve the preparation process of Moutan Cortex formula granules, paeonol was quickly recovered by using volatile oil collection device in the process of vacuum concentration, and the collected paeonol was added back to the concent rated solution.Then, the formula granules of Moutan Cortex were prepared by spray drying and dry granulating.The correlation between the decoction pieces, extract, concentrate, powder, formula granules and standard decoction were compared by taking the contents of paeoniflorin, paeonol and fingerprint as indexes. RESULTS: The range of parameters for Moutan Cortex standard decoction(70%-130% of the average value) were as follows:the dry extract rate was 19.46%-36.14%. The content of paeoniflorin was in the range of 1.83%-3.40%, and the transfer rate was 60.32%-100.00%. The content of paeonol was 1.25%-2.33%, and the transfer rate was 14.42%-26.78%.The contents of paeoniflorin and paeonol in the formula granules of Moutan Cortex conformed to the range of standard decoction parameters. CONCLUSION: The parameters of Moutan Cortex standard decoctions prepared by decocting pot are confirmed, and a new preparation process of Moutan Cortex formula granules is established.Both of standard decoction and formula granules have good consistency in the contents of the index components,which could provide a certain scientific basis for the guidance of actual production.
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Objective Process design grants the quality connotation to products. To study the changes of main chemical ingredient of Scutellaria baicalensis preparation in the preparation process and the correlation with its pharmacological activity. To clarify the key step of S. baicalensis preparation process, and overall evaluate the short plate of the quality of preparation from the perspective of the design. Methods The preparation process (extracting-concentrating-drying-granulation) was simulated. HPLC analysis was employed to determine the contents of the chemical ingredients in each step of preparation process. Induction by LPS in mouse peritoneal macrophages of each intermediate was used as the model to determinate the anti-inflammatory activity. Cluster analysis and linear regression were used to analyze the correlation between its chromatogram and pharmacological activity. Results The content of chemical ingredients and anti-inflammatory activity of S. baicalensis were generally decreased on the whole, and the highest loss occurred in the concentrating-drying process. Conclusion Each step of the preparation process of S. baicalensis preparation has significant effect on the chemical ingredients and pharmacological activity. The concentrating and drying process may be the key process which could finally influence the quality of preparation.
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objective To optimize the preparation technology of sulfuric in situ gel and study the infiltration experiment of different dosage forms. Methods Shufei in situ gel was prepared by cold cut method with poloxamer 188 (P188) and poloxamer 407 (P407) as gel base. Using gelling temperature index, the dosage range of gel matrix P407 and P188 in Shufei in situ gel was determinated by the single factor and star design-response surface methods to get the best prescription of Shufei in situ gel. The transdermal diffusion process of Shufei in situ gel was carried out in Franz diffusion cells to explore the permeation mechanism. Results The optimized prescription of Shufei in situ gel was as follow: The ratio of gel matrix to drug at 1:3, P188 dosage of 4%, P407 dosage of 22.5%, and the phase transition temperature within 32-36 ℃ to form gel. The releases of sinapine thiocyanate and genkwanin in Shufei in situ gel were all in line with the Higuchi release model. Conclusion The preparation process of Shufei in situ gel is stable and feasible with reliable product quality and good application prospect, which is suitable for industrial production and clinical application.
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Objective To optimize the formulation ratio and preparation process of galactosylated cantharidin liposome (Lac-CTD- lips) and establish its methodology for content determination. Methods The method of determination of GC-MS cantharidin content was established by film dispersion method. The entrapment efficiency of cantharidin was evaluated as an index. The preparation process of Lac-CTD-lips was optimized by single factor and orthogonal experiments. Its surface characteristics, encapsulation efficiency, particle size, and Zeta potential were also investigated. Results The best prescription was as follow: cantharidin: hydrogenated soya lecithin:cholesterol at 1:20:5, 10% galactoside, film-forming at 50 ℃, film cleaning with 30 mL of PBS solution of pH 6.0, and hydartion at 40 ℃ for 1.5 h. The resulting liposomes exhibited a pale blue opalescent appearance, a spherical particle morphology, and a more rounded surface with no adhesion. The average particle size was (123.9 ± 4.8) nm (n = 3), the particle size distribution was single-peak, the zeta potential was (-0.36 ± 0.81) mV (n = 3), and the encapsulation efficiency was over 75%. Conclusion GC-MS is suitable for the determination and analysis of cantharidin content. The optimal preparation technology from orthogonal experiment is stable and reliable. The obtained liposomes have higher encapsulation efficiency, small particle size, and good appearance.
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Chinese materia medica (CMM) compound is the main form and method of clinical drug in traditional Chinese medicine. On the basis of guaranteeing the safety, efficiency, stability, and controllability of CMM compound preparations, it is particularly important to rationally design process routes, production equipment, and quality control methods, and to establish a processing research model which conforms to the characteristics of CMM compound preparations. According to the status of policy, process, and equipment of CMM compound preparations, we analyze the technological mode of CMM compound preparations using holistic view, dynamic view, and dialectical view, break through the difficulties of this study, and propose research strategies for the development of CMM compound preparations, hoping to provide references for the preparation of CMM compound formulations.
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Objective To prepare and characterize tri-components nanostructure lipid carrier of Ginseng Radix modified with hyaluronic acid (HA-OUR-NLC). Methods Nanostructured lipid carriers (NLC) was used to wrap mount three difficult soluble active ingredients in Ginseng Radix including oleanolic acid (OA), ursolic acid (UA), and ginsenoside Rg3. Then using hyaluronic acid (HA) as the target factor, NLC was modified by charge-adsorption. The dynamic dialysis method was used to test the release. The cellular uptake and cytotoxicity of HA-OUR-NLC on SMMC-7721 cells were investigated by flow cytometry instrument and MTT assay respectively. Results OUR-NLC was prepared by ultrasonic dispersion of solvent using NLC as carrier material and CTAB as emulsifier, and its appearance was light blue opalescence. Then HA-OUR-NLC was successfully prepared by charge-sorption method with round shape and uniform distribution. In vitro release showed that it had a sustained release effect. Cell uptake experiments showed that HA-OUR-NLC can be taken up by SMMC-7721 cells. MTT assay results showed that HA-OUR-NLC had inhibitory effect on SMMC-7721 cell proliferation. Conclusion HA-OUR-NLC prepared by solvent ultrasonic dispersion not only has good physical and chemical properties, but also has a certain sustained release effect.