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@#In order to develop a more effective drug for dry eye disease, the preparation of lifitegrast eye drops was carried out, and the safety and efficacy of lifitegrast eye drops in vitro and in vivo were investigated. First the method for the determination of lifitegrast content was established, and then the composition and preparation process of the preparation were determined by literature review and single factor experiment. Finally, the safety of lifitegrast eye drops was evaluated by Draize eye irritation test and HE staining, and the therapeutic efficacy was evaluated by Schirmer test and ELISA test. The results showed that the final prescription of lifitegrast eye drops consisted of 5% lifitegrast, 0.4% sodium chloride, 0.3%−0.4% anhydrous disodium hydrogen phosphate, 0.3% sodium thiosulfate pentahydrate and 0.3% sodium hydroxide. The appearance of lifitegrast eye drops was transparent and slightly brownish yellow solution, the pH was7.75±0.05, the osmotic pressure was in the range of 200−330 mOsmol/kg and it had good stability at 60℃ for 3 months. There was no significant difference in irritation study compared with normal saline. Schirmer test showed that tear secretion was increased and the expression of inflammatory factors IL-6, IL-1β and TNF-α in tears were significantly decreased after treatment with lifitegrast eye drops and compared to the commercially available emulsion cyclosporine eye drops, it takes effect faster. The above results indicate that lifitegrast eye drops are simple to prepare and stable, which is a better choice for the rapid treatment of dry eye disease.
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This article discussed the evolution of the traditional preparation process of Pinelliae Rhizoma Fermentata.The production methods for Pinelliae Rhizoma Fermentata in Song Dynasty include cake-making of Pinelliae Rhizoma together with ginger juice and fermentation after cake-making,and the former method of cake-making was the mainstream.The process technology in Jin and Yuan Dynasties inherited from that in Song Dynasty,and the application of Pinelliae Rhizoma Fermentata had certain limitations.The medical practitioners of Ming Dynasty elucidated the mechanism of processing of Pinelliae Rhizoma Fermentata,and proposed the view of"sliced Pinelliae Rhizoma being potent while fermented Pinelliae Rhizoma being mild".In the Ming Dynasty,LI Shi-Zhen defined the cake-making process and fermentation process for Pinelliae Rhizoma,and HAN Mao's Han Shi Yi Tong(Han's Clear View of Medicine)contained five prescriptions for the processing of Pinelliae Rhizoma Fermentata,which had the epoch-making signficance in the expansion of prescriptions for the processing of Pinelliae Rhizoma Fermentata.In the Qing Dynasty,HAN Fei-Xia's ten methods for making Pinelliae Rhizoma Fermentata were summarized on the basis of the methods recorded in Han Shi Yi Tong,and at that time,the processing of Pinelliae Rhizoma Fermentata and the preparation of Massa Medicata Fermentata interacted with each other.After the founding of the People's Republic of China,the local experience in the preparation of Pinelliae Rhizoma Fermentata was deeply influenced by the methods in the Qing Dynasty,and the local preparation technical standards gradually became the same.Moreover,this article also explored the issues of the importance of"Pinelliae Rhizoma"and"ingredients for fermentation",the pre-treatment of Pinelliae Rhizoma,the distinction between cake-making process and fermentation process for Pinelliae Rhizoma,the amount of flour added as well as the timing of adding,the addition of Massa Medicata Fermentata powder,the role of Alum in Pinelliae Rhizoma Fermentata and so on.
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AIM To prepare the nanosuspensions of naringenin phospholipids complex,and to investigate their in vivo pharmacokinetics.METHODS High-pressure homogenization method was applied to preparing the nanosuspensions of phospholipids complex.With stabilizer type,stabilizer-phospholipids complex consumption ratio,homogeneous pressure and homogeneous frequency as influencing factors,particle size,PDI and Zeta potential as evaluation indices,the formulation was optimized by single factor test.The morphology was observed under transmission electron microscope,after which X-ray powder diffraction analysis was performed,solubility,oil-water partition coefficient,dissociation rate of phospholipids complex and accumulative release rate were determined.Twenty-four rats were randomly assigned into four groups and given intragastric administration of the 0.5%CMC-Na suspensions of naringenin and its phospholipids complex,nanosuspensions and nanosuspensions of phospholipids complex(30 mg/kg),respectively,after which blood collection was made at 0,0.25,0.5,1,1.5,2,3,4,5,6,8,10,12 h,HPLC was adopted in the plasma concentration determination of naringenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 50 mg for naringenin consumption,PVP K30+TPGS(1 ∶ 1)as stabilizer,3 ∶ 1 for stabilizer-phospholipids complex consumption ratio,100 MPa for homogeneous pressure,and 10 times for homogeneous frequency,respectively.The obtained spherical-like or oval nanosuspensions of phospholipids complex demonstrated the average particle size,PDI and Zeta potential of(260.53±25.86)nm,0.160±0.024 and(-31.08±1.37)mV,respectively.Naringenin existed in the nanosuspensions of phospholipids complex in an anamorphous state,along with increased solubility,oil-water partition coefficient and dissociation rate of phospholipids complex,and the accumulative release rate reached more than 90%within 4 h.Compared with raw medicine and nanosuspensions,the nanosuspensions of phospholipids complex displayed shortened tmax(P<0.05)and increased Cmax,AUC0-t,AUC0-∞(P<0.05,P<0.01),the relative bioavailability was enhanced to 4.38 times.CONCLUSION The nanosuspensions of phospholipids can enhance naringenin's solubility and dissolution rate,and promote its in vivo absorption.
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AIM To prepare andrographolide self-microemulsifying drug delivery system.METHODS The range of excipient ratio was determined according to equilibrium solubility,excipient compatibility and pseudo-ternary phase diagram.With Pogostemon cablin oil proportion,Labrasol ALF-Tween 80 ratio and Km as influencing factors,drug loading as an evaluation index,the formulation was optimized by central composite design-response surface method,after which in vitro evaluation was performed.RESULTS The optimized formulation was determined to be 10.45%,13.28%,9.82%,66.44%for Pogostemon cablin oil,Labrasol ALF,Tween 80,Transcutol HP proportions,the equilibrium solubility was(11.95±0.04)mg/g.The quality parameters were(20.22±0.38)s for emulsification time,(51.70±2.91)nm for particle size,0.27±0.02 for polydispersity index,and(91.21±1.58)%for light transmission rate,respectively.The self-microemulsion drug delivery system demonstrated good freeze-thaw stability,whose particle size was not obviously influenced by dilution times and dispersion medium,and was rapidly dissolved in phosphate buffer solution(pH 6.8).CONCLUSION Self-microemulsifying drug delivery system can enhance the solubility and dissolution rate of andrographolide.
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AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.
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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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Medicamentos Herbarios Chinos , Medicina Tradicional China , PrescripcionesRESUMEN
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 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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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 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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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 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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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 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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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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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.