Preparation and quality evaluation of total flavonoids microemulsion of "Pueraria lobata-Hovenia dulcis" / 中国中药杂志

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.

Preparation and in vitro evaluation of berberine hydrochloride nanoemulsion oral drug delivery systems / 药学实践杂志

Objective To prepare berberine hydrochloride nanoemulsion, optimize its formulation composition and preparation process, and investigate its in vitro characteristics. Methods BBR-NE was prepared by water drop addition and pseudo-ternary phase diagram was drawn. The formulation of NE was optimized by central composite design-response surface methodology to choose the optimal formulation composition. The particle size, potential and appearance of the prepared BBR-NE were characterized. Results The optimal prescription of BBR-NE was determined as the oil phase Capryol 90 accounted for 32.84% of the system, the surfactant Tween-80 accounted for 33.90%, the co-surfactant 1,2-propylene glycol accounted for 16.95%, and water relative system accounted for 15.25%. The prepared NE was clear and transparent in appearance, regular in shape and uniform in size, with an average particle diameter of (68.85±8) nm, polydiseperse index of (0.245±0.03) and drug loading of 0.83 mg/g. The in vitro drug release results of NE showed that the in vitro drug release behavior was passive diffusion, which had a certain slow releasing effect and met the first-order release equation. Conclusion The BBR-NE can provide a new dosage form for the clinical use of berberine.

Preparation of nanoemulsion spray from Moslae Herba volatile oil and its antibacterial activity / 中国中药杂志

Moslae Herba is a commonly used aromatic Chinese medicinal with volatile oil as the main effective component and exhibits broad-spectrum antibacterial and antiviral effects. However, the irritation and instability of Moslae Herba volatile oil necessitate the preparation into a specific dosage form. In this study, the steam distillation method was employed to extract the Moslae Herba volatile oil. The content of thymol and carvacrol in Moslae Herba volatile oil was determined by HPLC as(0.111 9±0.001 0) and(0.235 4±0.004 7) mg·mL~(-1), respectively. Pseudo-ternary phase diagrams and surfactants compounding were applied in the selection of the optimal excipients(surfactant and cosurfactant). On this basis, a nanoemulsion was prepared from the Moslae Herba volatile oil and then loaded into pressure vessels to get sprays, whose stability and antibacterial activity were evaluated afterward. With clarity, viscosity, smell and body feeling as comprehensive indexes, the optimal formulation of the Moslae Herba volatile oil nanoemulsion was determined as follows: Moslae Herba volatile oil∶peppermint oil∶cremophor EL∶absolute ethanol∶distilled water 7.78∶1.58∶19.26∶6.15∶65.23. The as-prepared nanoemulsion was a light yellow transparent liquid, with Tyndall effect shown under the irradiation of parallel light. It has the pH of 5.50, conductivity of 125.9 μS·cm~(-1), average particle size of 15.45 nm, polydispersity index(PDI) of 0.156, and Zeta potential of-17.9 mV. Under a transmission electron microscope, the Moslae Herba volatile oil nanoemulsion was presented as regular spheres without adhesion and agglomeration. Stability test revealed that the Moslae Herba volatile oil nanoemulsion was stable at 4-55 ℃, which was free from demulsification and stratification within 30 days. After the centrifugation at 12 000 r·min~(-1) for 30 min, there was no stratification either. The nanoemulsion had good inhibitory effects on Escherichia coli, Staphylococcus aureus and resistant S. aureus strains, with the minimum inhibitory concentrations of 0.39, 3.12 and 1.56 mg·mL~(-1), respectively. The above results demonstrated that the nanoemulsion was prepared feasibly and showed stable physical and chemical properties and good antibacterial effects. This study provides a practicable technical solution for the development of anti-epidemic and anti-infection products from Moslae Herba volatile oil.

Preparation of citronellol self-emulsifying delivery system and evaluation of its in vitro antitumor activity / 中草药

Objective: To investigate the effect of citronellol (citronellol, CT) on the proliferation of HEp-2 and MCF-7 cells, and prepare CT self-emulsifying drug delivery system (CT-SMs). Its antitumor activity and cell uptake ability of HEp-2 cells in vitro was evaluated. Methods: The effect of CT on the cell proliferation of HEp-2 and MCF-7 were investigated by MTT assay. The pseudo- ternary phase diagram method was used to optimize the formulation of CT-SMs, and the appearance morphology, mean particle size, and Zeta potential were characterized. The effect of CT-SMs on the proliferation of HEp-2 cells was detected by MTT assay and cellular uptake was determined by fluorescence inversion microscopy and flow cytometry. Results: After a certain concentration of CT treatment, MCF-7 cells proliferation was not affected, and the difference was not statistically significant (P > 0.05 compared with the control group), while the proliferative capacity of HEp-2 cells was significantly inhibited (P < 0.05 compared with the control group) in a dose-time dependent manner. The best prescription for CT-SMs was as following: Km (emulsifier:co-emulsifier) was Kolliphor® HS 15:absolute ethanol = 7:3, CT:Km = 3:7, the mean particle size was (354.0 ± 9.5) nm, the appearance was round and spherical with uniform distribution, and the Zeta potential was (-13.4 ± 0.3) mV. The results of cellular uptake experiments showed that the intake of CT-SMs (545.70 ± 11.56) was higher than that of CT (230.00 ± 17.76) in HEp-2 cells treating the same concentration of CT-SMs and CT. Conclusion: CT-SMs could significantly inhibit the proliferation of HEp-2 cells. In this study, CT-SMs were successfully prepared by dropping water method and the quality of CT-SMs was stable and controllable.

Preparation, quality evaluation and cell uptake of 1,8-cineole self-microemulsion drug delivery system / 中草药

Objective: To optimize the formulation of 1,8-cineole self-microemulsifying drug delivery system (1,8-Cin-SMEDDS), characterize it and investigate its cell uptake. Methods: By drawing pseudo-ternary phase diagram, the effective self-emulsifying region of 1,8-Cin-SMEDDS was determined, and the preliminary prescription was screened. Taking the particle size and drug loading as the index, the central composite design-response surface method was used to optimize and verify the prescription. Fluorescence microscope was used to observe the uptake of human umbilical vein endothelial cells (HUVEC) injured by high glucose. Results: The results showed that the best prescription of 1,8-Cin-SMEDDS was a mixture of soybean oil (7.5%) and 1,8-Cin (22.5%), HS15 (56%) as emulsifier, ethanol (14%) as co-emulsifier, and dripping pure water to 8 mL to obtain a translucent slightly bluish emulsion. The appearance of spherical droplets was observed by transmission electron microscope, and the average particle size and Zeta potential measured by laser particle size Zeta tester was (131.68 ± 1.44) nm and (-10.03 ± 1.63) mV, respectively; The entrapment efficiency estimated by HPLC was (99.890 ± 0.012)%, and the drug loading was (224.750 ± 0.028) mg/g. The results of HUVEC cell uptake assay showed that the uptake of 1,8-Cin-SMEDDS by cells was higher than that of free 1,8-Cin. Conclusion: The preparation method of 1,8-Cin-SMEDDS is simple and reproducible. The obtained method has good appearance, high entrapment efficiency, stable physical, and chemical properties, which can also promote cell uptake.

Preparation of self-microemulsion gel drug delivery system of Carthamus tinctorius extract based on Mentha haplocalyx oil as oil phase / 中草药

Objective: To prepare the self-microemulsion gel drug delivery system of Carthamus tinctorius extract based on Mentha haplocalyx oil as oil phase. Methods: M. haplocalyx oil was used as the oil phase, and C. tinctorius extract was used as the water phase. The prescription of self-microemulsion were optimized by pseudo-ternary phase diagram, the process and prescription of gel were screened by single-factor method and the appearance, viscosity and pH value were evaluated. Result: The optimal formulation of CTE-SMEDDS-BGs was as following: F68 was the emulsifier, anhydrous ethanol was the co-emulsifier, the Km ratio was 1:1, and the total amount of emulsifier and co-emulsifier to M. plocalyx oil was 8:2, carbopol-980 was 2%, glycerin was 6%, and C. tinctorius extract was 5 mL. The CTE-SMEDDS-BGs was obtained by adding the CTE-SMEDDS into swelling gel matrix and triethylamine was used to adjust the pH to 6.0. The characteristics of appearance were yellow translucent, moderate viscosity, uniform and delicate, non-greasy, and easy to spread on the skin, the viscosity was 4.98 × 104 mPa•s (RSD was 1.53%), pH was 6.04 (RSD was 0.44%). Conclusion: The CTE- SMEDDS-BGs with M. plocalyx oil as oil phase is simple and stable, and meets the requirements of gel topical preparations.

Study on prescription process of nanoemulsion of Perilla frutescens essential oil and preliminary quality evaluation / 中草药

Objective: Using Perilla frutescens as a model drug, the nanoemulsion of Perilla frutescens essential oil (PFEO) were prepared, and the formulation process research and preliminary quality evaluation were carried out. Methods: The cosurfactants were determined according to the amount of PFEO dissolved in various excipients. The HLB value method was used to preliminarily screen surfactants suitable for oil-in-water (O/W) nanoemulsions, and the surfactants with dosage safety were further screened to determine the composition of nanoemulsion formulations. By drawing a pseudo-ternary phase diagram, the nanoemulsion region size, drug loading, water content, and conductivity, viscosity, particle size, distribution, and stability was comprehensively compared to optimize the prescription. This study investigated the appearance, physicochemical properties (viscosity, pH value, conductivity, electrical conductivity, particle size, Zeta potential), stability, in vitro permeability properties and nasal mucosa irritation of the nanoemulsion of PFEO. Results: The final optimized nanoemulsion formulation was 14.3% PFEO-9.5% Transcutol P-19.1% Labrasol-57.1% water. The nanoemulsion of PFEO prepared according to the optimized prescription was uniform, transparent, clear, with good fluidity. The viscosity was (3.68 ± 0.17) mPa∙s, pH value was (6.18 ± 0.03), the electrical conductivity was (109.61 ± 0.89) μS/cm, the Zeta potential was (-7.08 ± 1.82) mV, and the particle size was (49.98 ± 1.55) nm. The results of transmission electron microscope experiment showed that, the droplets of PFEO nanoemulsion were spherical with the particle size within 100 nm. The stability test results showed that the nanoemulsion of PFEO had centrifugal stability, dilution stability, long-term stability and temperature stability. After storage at room temperature and unsealed for one month and six months, the percentage change of the average perillaldehyde content of PFEO nanoemulsion and PFEO was 1.8% and 17.48%, respectively. The nasal mucosal irritation test results showed that the PFEO nanoemulsion administration group had no significant difference from the blank saline group. Conclusion: The appearance and related physical and chemical properties of PFEO nanoemulsion prepared by optimized prescription process meet the quality requirements of nanoemulsion, with drug stability, drug permeability and safety.

Effect of precipitation inhibitors on pH-induced supersaturated phase behavior of dl-tetrahydropalmatine / 中草药

Objective: To investigate the effect of three types of precipitation inhibitors (PPI) HPMC K4M, HPMC AS MG and Soluplus on the pH-induced supersaturated phase behavior of dl-tetrahydropalmatine (dl-THP) at oral clinical doses. Methods: dl-THP pH solubility phase diagram and desaturation curve during pH-shift were drawn, and the solubility phase diagram was used to support dl-THP phase behavior. Area under the concentration-time curve and supersaturation ratio were used to analyze the effect of PPI on the phase behavior of dl-THP; Polarized light microscope and differential scanning calorimetry were used to analyze the precipitation properties. Results: Under the clinical dosage, the maximum supersaturation of dl-THP during the pH-shift was 3.93, and the supersaturation was lost over time; HPMC K4M, HPMC AS MG, and Soluplus could all maintain the supersaturation within 180 minutes during the pH-shift dissolution. HPMC K4M, HPMC AS MG, and Soluplus maintained supersaturation levels of 1.19, 1.89 and 1.36 respectively at a concentration of 5%, 1.30, 2.35 and 1.86 at a concentration of 20%, and 1.30, 2.60 and 2.07 at a concentration of 50%. Polarized light microscopy and differential scanning calorimetry results showed that crystalline precipitation occurred. Conclusion: All precipitation inhibitors can improve the pH-induced supersaturated phase behavior of tetrahydropalmatine, and this improvement behavior varies with the type and concentration of precipitation inhibitors. HPMC AS MG has the best effect.

Preparation and in vitro quality evaluation of self-microemulsion co-loaded with tenuifolin and β-asarone / 中国中药杂志

To prepare and optimize the self-microemulsion co-loaded with tenuifolin and β-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g~(-1) for tenuifolin and(5.526±0.022) mg·g~(-1) for β-asarone; uniform and transparent pan-blue nanoemulsion can be formed after emulsification, with particle size of(28.84±0.44) nm. TEM showed that TF/ASA-SMEDDS can form spherical droplets with a uniform particle size after emulsification; In vitro release test results showed that the drug release rate and cumulative release of tenuifolin and β-asarone were significantly improved. The preparation process of TF/ASA-SMEDDS was simple and can effectively improve in vitro release of tenuifolin and β-asarone.

Preparation and Evaluation of Weisu Microemulsion-Ion Sensitive Gel / 中国药学杂志

OBJECTIVE: To design and evaluate the formula of Weisu microemulsion-ion sensitive gel. METHODS The prescription of microemulsion-ion sensitive gel was conducted on the basis of single factor method and pseudotemary phase diagram method combining with central composite design-response surface methodology. The final formulation was evaluated by particle size, viscosity, potential, contents of naringin, hesperidin and neohesperidin. RESULTS: The optimum prescription ratio of Weisu microemulsion-ion sensitive gel was as following:volatile oil 3 g, RH-40 9 g, PEG-400 3 g, 0.3% deacetylated gellan gum made into 333 mL microemulsion gel. The results of physicochemical properties showed that microemulsion gel appearance was clear. The particle diameter was 20.14 nm. The Zeta potential was -4.04 mV. pH value was 5.43. The contents of naringin, hesperidin and neohesperidin are respectively 6.122 4, 2.094 1, 4.277 mg•mL-1. CONCLUSION: The preparation process of Weisu microemulsion gel is reasonable and feasible. The prepared microemulsion gel is system are stable.

Preparation and Formulation Optimization of Ketoprofen Microemulsion-based Gel / 中国药学杂志

OBJECTIVE: To prepare the ketoprofen microemulsion-based gel in order to expand its drug loading and increase the transdermal permeability. METHODS: The proportion range of oil phase/surfactant in ketoprofen microemulsion were screened by the pseudo-ternary phase diagram. Optimization of formulation for microemulsion gels was conducted by central composite design-response surface methodology with the cumulative permeation quantity across in vitro rat skin and time-lag as evaluation indexes.The transdermal performance of self prepared gel was compared with the commercially available gel. RESULTS: The optimal oil phase, surfactant and cosurfactant of ketoprofen microemulsion were oleic acid, polyoxy ethylene castor oil (EL-35) and ethanol, respectively.The optimal microemulsion formulation was 1.35% oleic acid, 10.8% EL-35, and 9% ethanol by central composite design experiment. The cumulative penetration quantity in 24 h reached 562.82 μg•cm-2 in vitro rat skin was 1.35 times as much as commercially available gel. CONCLUSION: The ketoprofen microemulsion-based gel prepared in this study has good permeability, which lay the foundation for development of the gel.

Optimization of Formulation of Econazole Solid Lipid Nanoparticles Based on Pseudo-ternary Phase Diagrams and Central Composite Design-Response Surface Methodology / 中国药学杂志

OBJECTIVE: To optimize the formulation of econazole solid lipid nanoparticles(E-SLN) by combining pseudo-ternary phase diagrams and central composite design-response surface methodology (CCD-RSM). METHODS: Econazole solubility in different solid lipids and the capacity of lipid emulsion were tested. The microemulsion region was obtained by the pseudo-ternary phase diagrams. Then the E-SLN were prepared by microemulsion method. Drug/lipid (X1), lipid/surfactant (X2) and surfactant/cosurfactant (X3) were taken as individual factors, the encapsulation efficiency (Y1), particle size (Y2), Zeta potential (Y3) were taken as the dependent factors. The possible optimum formulation was predicted by CCD-RSM and validated. RESULTS: Econazole could be dissolved in tripalmitic acid glyceride (TAG), monostearic acid glyceride, stearic acid and lauric acid glyceride. TAG had a good capacity of emulsion. The optimized formulation was econazole 0.06 g, glyceryl palmitate 0.48 g, Tween-80 1.194 g, glycerol 0.274 g and added water to 30 mL by CCD-RSM. According to the optimized formulation, the encapsulation efficiency, particle size and Zeta potential were (94.06±1.54)%, (18.88±0.38)nm and (3.53±0.01)mV, respectively. The deviation was less than 5%. CONCLUSION: The stable and ultra-small size E-SLN with high encapsulation efficiency could be obtained by combining pseudo-ternary phase diagrams and CCD-RSM.

Preparation of Oxymatrine Phospholipid Complex Solid Lipid Nanoparticles Lyophilized Powder and Evaluation of Its Quality / 中国实验方剂学杂志

Objective: To prepare oxymatrine phospholipid complex solid lipid nanoparticles(OMT-PC-SLN) lyophilized powder and evaluate its pharmaceutical properties. Method: Pseudo-ternary phase diagram was employed to optimize the formula of microemulsion;single factor experiments were adopted to optimize the formulation process of OMT-PC-SLN lyophilized powder with encapsulation efficiency as index;the morphology of this preparation was observed by transmission electron microscope(TEM).The particle size was measured by particle size analyzer and the in vitro release performance of OMT-PC-SLN lyophilized powder was examined. Result: Optimal formulation process was as following:taking soybean phospholipid and polyethylene glycol 15-hydroxystearate(Kolliphor HS 15) as the emulsifier,ethanol as co-emulsifier,ratio of emulsifier to co-emulsifier(Km)=3:2,oil phase:(emulsifier+co-emulsifier)=1:9,oxymatrine phospholipid complex-stearic acid-soybean phospholipid-Kolliphor HS 15-ethanol(30:100:180:360:360);taking 50 mL of 4%mannitol solution as the external aqueous phase,ice bath stirring at 1 000 r·min-1 and solidifying for 1 h,precooled at -20℃ for 24 h,took out and dried for 24 h.OMT-PC-SLN lyophilized powder was spherical in appearance with encapsulation efficiency of (38.09±1.24)%,average particle size of 785.5 nm,polydispersity coefficient(PDI) of 0.456 and the Zeta potential of -24.82 mV.The cumulative release rates of OMT-PC-SLN lyophilized powder were 72.63%at 2 h and 98.42%at 12 h;the cumulative release rate of oxymatrine(crude drug) was 98.60%at 2 h. Conclusion: This optimized formulation process of OMT-PC-SLN lyophilized powder is stable with good repeatability;compared with oxymatrine,OMT-PC-SLN lyophilized powder has a certain sustained-release effect.

Preparation of Lappaconitine-Loaded Microemulsion with Olive Oil and Research on Its Properties / 中国药学杂志

OBJECTIVE: To prepare lappaconitine(LA)-loaded microemulsion with olive oil and study its morphology, particle size, drug loading capacity, drug release behavior and rheological characteristics. METHODS: Pseudo-ternary phase diagram method was used to screen and prepare LA-loaded microemulsion with olive oil. LA release properties in vitro were investigated by dynamic dialysis method. The rheological properties of LA-loaded microemulsion with olive oil were studied using MCR 301 rheometer. RESULTS: The optimal formulation of LA-loaded microemulsion with olive oil was as follows:olive oil was the oil phase, castor oil polyoxyethylene ether-40/span-80(4:1) was the surfactant, glycerin was the cosurfactant, and Km=3. The morphology of the microemulsion particles was round or oval, and the average particle size was(91±0.55) nm. The drug-loading rate of LA in the microemulsion was 1.85%.Drug release experiments in vitro showed that the microemulsion had a sustained release effect on LA, and the drug release behavior was more suitable to be described by Higuchi equation. Rheological experiments showed that the fluid of LA-loaded microemulsion with olive oil belong to pseudoplastic fluid of non-Newtonian fluid exhibiting thixotropic and shear-thinning fluid behavior as well as certain viscoelasticity. CONCLUSION: The LA-loaded microemulsion witholive oil are successfully prepared, and the microemulsion has ideal sustained release behavior and good rheological properties. The study provides a foundation for the developmenton preparation of LA-loaded microemulsion with olive oil.

Preparation and quality evaluation of Acori Tatarinowii Rhizoma-volatile oil microemulsion / 中草药

Objective: Taking the volatile oil of Acori Tatarinowii Rhizoma with the effect of anti-senile dementia as model drug to prepare Acori Tatarinowii Rhizoma-volatile oil microemulsion (AO-ME). Methods: The composition of microemulsion was preliminarily determined according to the solubility of volatile oil from Acori Tatarinowii Rhizoma in various solvents. By drawing pseudo-ternary phase diagram, the optimal microemulsion formulation was selected according to the size of particles and microemulsion region, stability of preparations and drug loading. Results: The optimal microemulsion formulation was that volatile oil of Acori Tatarinowii Rhizoma-Cremophor EL-glycerol-water was 6.25:20.83:10.42:62.5. The average particle size of AO-ME was (30.5 ± 0.2) nm with a polydispersity index of 0.150 ± 0.002. The viscosity value of AO-ME was (2.80 ± 0.21) mPa∙s. In vitro transdermal rate of AO-ME was (1 288.76 ± 16.20) μg/(cm2∙h), measured in β-asarone. Compared with ordinary emulsion, the transdermal rate of AO-ME was increased 14 times. The ciliary toxicity test of toad showed that the preparation had no significant toxicity. Conclusion: The preparation of AO-ME was prepared with stable physicochemical properties, good transdermal properties, and low toxicity to nasal mucosa cilia.

Preparation of astragaloside IV self-microemulsifying drug delivery system and in situ intestinal absorption in rats / 中草药

Objective: To prepare astragaloside IV self-emulsifying drug release system (astragaloside IV SMEDDS), and investigate its intestinal absorption characteristics in rats. Methods: According to the solubility and compatibility of astragaloside IV in different oil phases, surfactants and cosurfactants, the prescription composition of astragaloside IV SMEDDS was determined. The dosage range of each component in the ideal microemulsion region was drawn by pseudo-ternary phase diagram, and the microstructure, particle size distribution and in vitro drug release of astragaloside IV SMEDDS after water dispersion were evaluated. The stability of astragaloside IV SMEDDS diluted with simulated human physiological body fluid was investigated, and the intestinal absorption kinetics of astragaloside IV self-microemulsion in rats was investigated by intestinal reflux test in rats. Results: The prescription of astragaloside IV SMEDDS was composed of Capmul MCM, Tween-80, and Transcutol H. Astragaloside IV SMEDDS was prepared by water dispersion to form a light blue emulsion microemulsion, and the uniform size of the microemulsion could be observed under transmission electron microscope, and the microemulsion was prepared by selecting a certain amount of astragaloside IV in any prescription dosage in the microemulsion formation region. The light blue emulsion microemulsion could be observed under transmission electron microscope. The average particle size of astragaloside IV SMEDDS was (45.4 ± 5.8) nm; The dissolution rate of astragaloside IV in the three dissolution media was significantly increased, and the microemulsion formed by astragaloside IV had good physical stability in simulated human physiological liquid. The absorption rate of astragaloside IV microemulsion in the whole intestine of rats was significantly higher than that of astragaloside IV suspension. Conclusion: The preparation of astragaloside IV into SMEDDS can increase the dissolution rate of the drug, enhance the absorption of the drug in the intestinal tract, which is expected to improve the oral bioavailability of astragaloside IV.

Preparation of ligustrazine microemulsion and comparative study on in vitro release of different size microemulsions / 中草药

Objective: To study the preparation process of ligustrazine microemulsion delivery system and evaluate its physical pharmacy properties; Microemulsions of different particle sizes were prepared in different oil phases, and the effect of particle size factors on the release behavior of the preparation was investigated. Methods: Taking the solubility of ligustrazine as index, the oil phase, emulsifier, and co-emulsifier were screened. The microemulsion formulation was optimized by pseudo-ternary phase diagram method. The encapsulation efficiency and drug loading was studied by ultrafiltration centrifugation. The particle size and potential were detected by the particle size analyzer. The release behavior of microemulsions with different particle sizes was compared by dialysis bag method. Results: The tetramethylpyrazine microemulsion was successfully prepared, and the appearance was clear and transparent. The average pH value was about 5.46. The detection method of microemulsion encapsulation rate was successfully established. When the drug loading of ligustrazine was 1.2 mg/mL, the encapsulation efficiency was (87.43 ± 0.20)%. The microemulsions of different particle sizes were prepared by changing the oil phase (ethyl oleate, oleic acid, and IPM). When the drug loading was 1.2 mg/mL, the three particle sizes were (16.80 ± 0.91), (129.50 ± 1.21), and (18.51 ± 0.24) nm, respectively. The release test showed that the release rate of all three could reach more than 90% within 4 h, and there was no significant difference. Conclusion: The uniform and stable tetramethylpyrazine microemulsion is successfully prepared; The release behavior of different tetramethylpyrazine microemulsions is not affected by the particle size factor.

Preparation of Cinacalcet Nanoemulsion and Its In Vivo and In Vitro Evaluation / 中国药学杂志

OBJECTIVE: To improve the dissolution and oral bioavailability of cinacalcet in fasted state by preparing cinacalcet nanoemulsion. METHODS: The oil phase, emulsifiers and co-emulsifiers were selected by solubility test and phase diagram studies. The dissolution in vitro and bioavailability in Bealge dogs of cinacalcet nanoemulsion were evaluated. RESULTS: The cinacalcet nanoemulsion was prepared with oleic acid(as oil phase), OP-10 (as emulsifier), PEG200 (as co-emulsifier) and water (W-W=3:8:4:15) and showed goog physical properties with regular round appearance. The average particle size of cinacalcet nanoemulsion was (24.1±3.8) nm. The poly-dispersity index (PDI) and Zeta potential were (0.261±0.032) and (-26.1±1.7) mV, respectively, which proved that the cinacalcet nanoemulsion formed a stable system. The in vitro dissolution of cinacalcet was significantly improved after being prepared into nanoemulsion. The pharmacokinetic study showed that the bioavailability of cinacalcet nanoemulsion was significantly enhanced in Beagle dogs in fasted state and the absorbtion of cinacalcet nanoemulsion had no difference in fed and fasted state. CONCLUSION: Cinacalcet nanoemulsion is easy to prepare and has small particle size, which can significantly improve the dissolution and bioavailability of cinacalcet in fasted state.

Preparation and quality evaluation of volatile oil from Acori Tatarinowii Rhizoma self-nanoemulsion / 中国中药杂志

In order to increase the solubility of volatile oil from Acori Tatarinowii Rhizoma, this study was to prepare self-nanoemulsion of volatile oil from Acori Tatarinowii Rhizoma . The prescriptions were preliminarily screened by miscibility studies, excipient compatibility tests, and pseudo-ternary phase diagrams, and then the optimal formulation was obtained by using the Box-Behnken response surface method, with particle size and drug-loading rate as the indicators. The self-nanoemulsion prepared by optimal prescription was characterized and evaluated for dissolution. The results showed that the optimal prescription for this volatile oil self-nanoemulsion was as follows: 41.7% volatile oil, 46.8% Tween-80, and 11.5% PEG-400. The prepared self-nanoemulsion was clear and transparent, with drug-loading of (192.77±1.64) mg·g⁻¹, particle diameter of (53.20±0.94) nm, polydispersity index of 0.230± 0.013, and Zeta potential of (-12.2±0.7) mV. The dissolution of self-nanoemulsion was higher than that of volatile oil. In this research, volatile oil served as the oil phase in self-nanoemulsion, so the prescription was simpler and the drug loading rate was higher. The prepared self-nanoemulsion complied with the relevant quality requirements, providing a reference for the preparation of volatile oil formulations.

Optimization of Preparation Technology of Rutin Nanoemulsion by Central Composite Design-Response Surface Method / 中国药师

Objective:To optimize the preparation technology of rutin nanoemulsion. Methods:The pseudoternary phase diagram of rutin nanoemulsion under the condition of different Kmwas drawn. With the drug loading and the particle size as the independent var-iables,and the percent of oil and the weight ratio of surfactant to cosurfactant as the dependent variables, the blank formula of rutin nanoemulsion was optimized by central composite design-response surface method. Results:The optimal formula was as follows:the ra-tio of ethyl oleate, cremopher RH40,1,2-propanediol and water was 7: 13: 5: 25. The average particle size of the prepared rutin nanoemulsion was 26.51 nm,and the drug loading was 8.97 mg·ml-1. Conclusion:The central composite design-response surface method can obtain a good formula of rutin nanoemulison,and the model has a good predictive function.