To optimize the formulation and preparation process of icaritin-coix seed oil microemulsion(IC-MEs) based on quality by design(QbD) concept. IC-MEs were prepared by water titration. Firstly, the risk factors that may affect the quality of IC-MEs were evaluated. Then Plackett-Burman design was used to screen out prescription factors and process parameters that had a significant effect on the indicators. Finally, Box-Behnken design was used to optimize the prescription ratio of IC-MEs. Through the risk assessment and Plackett-Burman design, three formulation factors [drug loading efficiency, the ratio of mixed-oil(coix seed oil-Glycerol tributyrate) to mixed-surfactant(HS15-RH40) and water addition] were determined as the key factors affecting IC-MEs. The regression model established by Box-Behnken design had a good predictability. The optimal formula was as following: the drug loading efficiency of 0.92%, the ratio of mixed-oil(coix seed oil-glycerol tributyrate) to mixed-surfactant(HS15-RH40) of 4∶6, and the water addition of 5.7 mL. According to this prescription, IC-MEs were prepared, and its encapsulation efficiency after 1 week was 92.45%±1.00%. Therefore, the stability of IC-MEs could be improved by optimizing prescription and process parameters of IC-MEs based on the QbD concept, which can provide certain reference value for the future development of IC-MEs.
Coix ; Emulsions ; Flavonoids ; Plant Oils

This study was mainly based on the compatibility of Puerariae Lobatae Radix and Chuanxiong Rhizoma to prepare submicron emulsion and evaluated its physical and pharmaceutical properties. Firstly, pseudo-ternary phase diagrams were drawn by dripping method which took Chuanxiong oil as the oil phase and the area of microemulsion region as the index. On this basis, suitable emulsifier and co-emulsifier were screened for the preparation of Chuanxiong oil submicron emulsion. Then, the formula realizing the largest oil loading was selected. Finally, puerarin substituted part of emulsifier and co-emulsifier to lower their content, so as to form puerarin-Chuanxiong oil submicron emulsion featuring the combination of medicine and adjuvant. Its particle size, zeta potential, centrifugal stability and storage stability were determined, and the in vitro drug release behavior was investigated by dialysis bag method, based on which the quality of the as-prepared submicron emulsion was evaluated comprehensively. The proposed method was proved feasible for the preparation of Chuanxiong oil submicron emulsion, which adopted polyoxyethylene castor oil(EL-40) as the emulsifier and was free from co-emulsifier. The formula of the maximum oil loading was found as Chuanxiong oil∶EL-40∶water 3∶7∶90. Further, puera-rin successfully replaced up to 10% of the emulsifier in submicron emulsion. Eventually, the optimal drug-loading formula was determined as puerarin∶Chuanxiong oil∶EL-40∶water 7∶30∶63∶900. The quality evaluation results of the as-prepared submicron emulsion demonstrated that the average emulsion droplet size was 333.9 nm, the PDI 0.26, and the zeta potential-10.12 mV. The submicron emulsion had a good centrifugal stability and did not present any instable phenomena such as delamination and precipitation during its standing still for 50 days. The evaluation of in vitro drug release behavior indicated that the submicron emulsion was capable of releasing the drug completely. The puerarin-chuanxiong oil submicron emulsion prepared in this study possessed a stable quality and to some extent increased the solubility of puerarin along with a sustained-release effect. This study provided ideas for the clinical application of puerarin.
Emulsions ; Isoflavones ; Particle Size ; Solubility

To decrease the hemolysis side effect of puerarin, the basic formula and preparation of puerarin submicron emulsion were optimized and the physicochemical properties were evaluated. Puerarin submicron emulsions were prepared by phase inversion-ultrasound combining with phospholipids complexes technology. The effects of preparative parameters, such as emulsification time, stirring velocity and ultrasound time, on mean diameter, span of dispersity, entrapment efficiency and overall desirability were investigated. The three dimensional response surface graphs were produced by second-order polynomial and liner equation, which predict the optimal experiment conditions. All response variables were found to be greatly dependent on three independent variables. Second-order polynomial equations were fitter than liner equations for this study. The optimal emulsification time, stirring velocity and ultrasound time was 15 min, 2 000 r x min(-1), 30 min, respectively. The mean diameter, span of dispersity, entrapment efficiency, drug content and zeta potential of emulsions prepared by the method were 228.23 nm, 0.628 4, 84. 32%, 9.98 mg x mL(-1), - 29.03 mV, respectively. Puerarin submicron emulsion was prepared by the optimized preparation method. The narrow particle diameter distribution, high envelopment efficacy and good stability were obtained. The physicochemical properties were suitable for the requirement of the intravenous emulsion.
Emulsions ; Isoflavones ; administration & dosage ; chemistry ; Particle Size

This study is to screen 23 blank O/W type microemulsion (ME) samples, that is 15 samples from our laboratory, and 8 samples from literature; compare the conductivity-water content curve (CWCC) method and visual method in determining the critical water content during O/W type MEs' formation, to analyze the deficiency and the feasibility of visual method and to exploxe scientific meanings of CWCC method in judging the critical water content of O/W type MEs during formation. The results show that there is a significant difference between the theoretical feasible CWCC method and visual method in determining the critical water content (P<0.001), and the results judged by conductivity is higher than that by eye-based water content. Therefore, this article firmly confirmed the shortcomings of visual method and suggested that the eye-base "critical water content" may falls into continuous ME stage during O/W MEs' formation. Further more, the CWCC method has theoretical feasibility and scientific meanings in determining the critical water content of O/W type MEs during formation.
Electric Conductivity ; Emulsions ; chemistry ; Water ; chemistry

PURPOSE: The chemoembolization with Lipiodol and doxorubicin hydrochloride is used in patients with hepatocellular carcinoma. What condition is the ideal emulsion of Lipiodol and doxorubicin for excellent anticancer effect? METHOD AND MATERIALS: Microscopic evaluation was performed on the emulsions, which were varied with different specific gravities of doxorubicin solutions, degrees in mixing of the emulsion, and amount of Lipiodol. RESULT: 1. Maximal amount of doxorubicin solution was contained in Lipiodol droplets and the release of doxorubicin from the droplets were delayed, when specific gravity of doxorubicin was equal to that of Lipiodol (SG, 1.28). 2. The optimal therapertic ratio of Lipiodol and doxorubicin was 3:2 at least, as in the emulsion less than 3:2, unmixed free forms of doxorubicin solution were increased. 3. The emulsion mixed by pumping 50--100 times had smaller Lipiodol droplets and contained larger amount of doxorubicin solution in the droplets than by pumping 20 times. CONCLUSION: We recommend the emulsion with specific gravity of doxorubicin equal to Lipiodol (SG. 1.28), the ratio of Lipiodol and doxorubicin closo to 3:2, and the mixture prepased with puming 50--100 times.
Carcinoma, Hepatocellular* ; Doxorubicin ; Emulsions ; Ethiodized Oil ; Humans ; Specific Gravity

OBJECTIVETo prepare the oridonin submicron emulsion and characterize their properties.

METHODHigh pressure homogenization method was employed to prepare the oridonin submicron emulsion and such properties as size, Zeta potential and viscosity were characterized.

RESULTThe results showed that the submicron emulsions was formed with the drug loading 1 g L(-1), particle size of (138.87 +/- 0.60) nm, zeta potential of (47.27 +/- 2.31) mV, pH value of (6.02 +/- 0.03) and viscosity of (1.78 +/- 0.015) MPa s, respectively.

CONCLUSIONThe method is feasible and the submicron emulsions has stable properties. Experiments offer a new formulation of oridonin for clinical application.

To improve mass transfer and enhance the yield for C(1,2) biodehydrogenation of steroid 11beta-hydroxyl medroxyprogesterone, we carried out the dehydrogenation reaction of 11beta-hydroxyl medroxyprogesterone in an oil-in-water (O/W) microemulsion by Arthrobacter simplex UR016. We studied the effects of system composition, dehydrogenation temperature and substrate concentration on microbial transformation. We formulated a suitable O/W microemulsion system with Arthrobacter simplex UR016 culture broth as aqueous phase, 10 g/L of edible oil as oil phase, 4 g/L of Tween-O80 and 7% (V/V) alcohol as surfactant and cosurfactant. The optimal dehydrogenation temperature was 33 degrees C. The results showed that in Tween-80/alcohol/edible oil/water microemulsion system, the hydrophobic steroid was solubilised and diffused effectively, with the maximum conversion rate of 88.6% at 46 h under 4 g/L substrate concentration, an increase of 66.2% compared to that in aqueous system. The C(1,2) biodehydrogenation of 11beta-hydroxyl medroxyprogesterone is more efficient in water-edible oil microemulsion system than in aqueous system.
Arthrobacter ; metabolism ; Biotransformation ; Emulsions ; Hydrogenation ; Medroxyprogesterone ; chemistry ; metabolism

Based on the demand of nasal drug delivery high drug loadings, using the unique phase transfer of solute, integrating the phospholipid complex preparation and submicron emulsion molding process of Scutellariae Radix extract, the study obtained the preparation of the high drug loadings submicron emulsion of Scutellariae Radix extract. In the study of drug solution dispersion method, the uniformity of drug dispersed as the evaluation index, the traditional mixing method, grinding, homogenate and solute phase transfer technology were investigated, and the solute phase transfer technology was adopted in the last. With the adoption of new technology, the drug loading capacity reached 1.33% (phospholipid complex was 4%). The drug loading capacity was improved significantly. The transfer of solute method and timing were studied as follows,join the oil phase when the volume of phospholipid complex anhydrous ethanol solution remaining 30%, the solute phase transfer was completed with the continued recycling of anhydrous ethanol. After drug dissolved away to oil phase, the preparation technology of colostrum was determined with the evaluation index of emulsion droplet form. The particle size of submicron emulsion, PDI and stability parameters were used as evaluation index, orthogonal methodology were adopted to optimize the submicron emulsion ingredient and main influential factors of high pressure homogenization technology. The optimized preparation technology of Scutellariae Radix extract nasal submicron emulsion is practical and stable.
Administration, Intranasal ; Emulsions ; Plant Extracts ; Technology, Pharmaceutical ; methods

OBJECTIVETo study the solubilization of O/W microemulsion system for volatile oil from Houttuynia Cordra and determine the formulation of its microemulsion.

METHODThe solubilization curve was drawn from pseudo-ternary phase diagram plotted by using the method of titration. The microemulsion's effect on solubilization for volatile oil from Houttuynia Cordra was systematically studied and the difference solubilization effects between colloid fluid and microemulsion were compared.

RESULTExcipient varieties and amount of microemulsion had effects on solubilization for volatile oil from Houttuynia Cordra. The formulation of its microemulsion was determined and we chose medium-chain triglycerides as oil phase, polyoxyethylene castor oil EL-35 as surfactant, propylene glycol as cosurfactant and the surfactant to cosurfactant ratio was 2.

CONCLUSIONSuitable microemulsion formulation can solubilize volatile oil from Houttuynia Cordra and it can provide research foundation for further development of microemulsion preparation for volatile oil from Houttuynia Cordra.

BACKGROUND: Lidocaine has been used widely to prevent propofol injection pain. Various methods of administration exist, such as lidocaine premixed with propofol or lidocaine pretreatment using a tourniquet, but it is unclear which method of lidocaine administration is more effective for the prevention of injection pain of propofol LCT/MCT. The purpose of this study was to compare pretreatment of lidocaine with a tourniquet and a premixed injection of lidocaine to prevent injection pain of propofol-LCT/MCT. METHODS: Patients were randomly allocated into the pretreatment group (n = 117) or the premixed group (n = 117). The pretreatment group was pretreated with 2 ml of lidocaine 2%, held with a tourniquet, before propofol-LCT/MCT injection. The premixed group was injected with a premixed solution of propofol-LCT/MCT and 2 ml of lidocaine 2%. To evaluate the incidence and severity of pain, spontaneous verbal expressions of pain, movement of hand, frowning, and moaning were recorded, and the patients were asked to recall their pain with the visual analogue score (VAS) 30 minutes after awakening from anesthesia. RESULTS: Overall, injection pain occurred in 13.7% of the pretreatment group and 15.4% of the premixed group, without any statistical difference (P = 0.71). There was no difference in spontaneous verbal expressions of pain, movement of hand, frowning, and moaning between the two groups. The pain intensity (VAS) also showed no difference between the two groups (P = 0.49). CONCLUSIONS: Pretreatment of lidocaine with a tourniquet showed no more benefit to prevent injection pain of propofol LCT/MCT compared to a premixed injection with lidocaine.
Anesthesia ; Emulsions ; Hand ; Humans ; Incidence ; Lidocaine* ; Methods ; Propofol ; Tourniquets*