OBJECTIVETo prepare and determine the proportion of the components of lidocaine microemulsion.

METHODSPseudoternary phase diagrams of the prepared lidocaine microemulsion with different Km (surfactant/cosurfactant) were generated to determine the optimal Km according to the size of the microemulsion area. The diameter and its distribution range, viscosity, electric conductivity and refractivity of lidocaine microemulsion drop was determined, and the appearance and system type of the microemulsion was observed using electron microscope. RESULTS; Maximum microemulsion area in the pseudoternary phase diagrams was obtained with the Km of 3, and the drop size of the microemulsion averaged 29.8+/-14.4 nm (with up to 98% of the drop size ranging between 15.1-45.5 nm and 2% between 77.9-261.3 nm). At 25 degrees C, the viscosity, electric conductivity and refractivity of the microemulsion was 25 mPa.S, 130 micros/cm and 1.473, respectively, and the lidocaine microemulsion was identified to belong to O/W type. The microemulsion drop appeared in spherical shape of heterogeneous sizes in a multi-disperse system.

CONCLUSIONThe optimal proportion of the components in lidocaine microemulsion can be obtained by analyzing pseudoternary phase diagrams, and the drop size, distribution, shape and system type can be determined or observed through Maerwen Zetasizer combined with electron microscopic observation.

Emulsifying Agents ; chemical synthesis ; Emulsions ; Lidocaine ; Microscopy, Electron, Transmission ; Surface-Active Agents ; chemistry

OBJECTIVETo study the feasibility of digalactosyl diglyceride (DGDG) , which was used as a new type of emulsifier to prepare submicro-emulsion of bay oil.

METHODBay oil was employed as the model drug, emulsifer in oil method was used to prepare foremilk. Through single factor investigation and central composite design-response surface methodology (CCD-RSM) , we optimized the preparation technology and formula respectively. The stability of sub-microemulsion was studied.

RESULTThe optima technology was following: emulsifer in oil method was used to prepare foremilk, temp was 60 degrees C, the micro emulsion was prepared by two-step high pressure homogen method with that the pressure was 80 Pa, 10 times, micropore film was used to sterilize, filling and sealing at the preservation of nitrogen. The best formula was following: soybean oil was 1.1%, DGDG was 1.6%, and sodium oleate was 0. 16%. The particle size of three batch submicro-emulsions were from 168.0 to 169.3 nm; Zeta potential were from-25.53 to 24.90 mV, pH value were from 8.48 to 8.52. The deviation between measured value and predictive value was 1.8%. It was stable in high temperature and illumination.

CONCLUSIONDGDG can be used as the emulsifier of bay oil sub-microemulsion.

Drug Stability ; Emulsifying Agents ; chemistry ; Emulsions ; chemistry ; Galactolipids ; chemistry ; Plant Oils ; chemistry ; Temperature

AIMTo evaluate the self-emulsifying ability and dissolution behavior of tretinoin in vitro and the pharmacokinetic behavior in beagle dogs.

METHODSThe self-emulsifying rate was evaluated by determining the intensity of scattered light at different time and the particle size of resultant emulsions after self-emulsifying were observed by optical microscope. The plasma concentrations were determined by HPLC and dissolution and pharmacokinetic behavior of self-emulsifying formulations were evaluated by comparison with commercial capsules.

RESULTSThe area under the curve (AUC) was significantly higher in the tretinoin self-emulsifying formulation group (3048.0 mg x h x L(-1)) than that in the commercial capsule group (1826.0 mg x h x L(-1)). Also, Tmax was smaller in the self-emulsifying formulation group (1.25 h) compared with market products (2 h) and the dissolved amount from self-emulsifying formulations in water at 15 min was much higher (more than 80%) than that of the market products (less than 5%).

CONCLUSIONThe self-emulsifying drug delivery systems can increase drug dissolution in vitro and absorption in vivo significantly.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Dogs ; Drug Delivery Systems ; Emulsifying Agents ; Emulsions ; Male ; Particle Size ; Polysorbates ; Solubility ; Tretinoin ; administration & dosage ; pharmacokinetics

Hydroxypropyl methylcellulose (HPMC) propels self-emulsifying drug delivery systems (SEDDS) to achieve the supersaturated state in gastrointestinal tract, which possesses important significance to enhance oral absorption for poorly water-soluble drugs. This study investigated capacities and mechanisms of HPMC with different viscosities (K4M, K15M and K100M) to inhibit drug precipitation of SEDDS in the simulated gastrointestinal tract environment in vitro. The results showed that HPMC inhibited drug precipitation during the dispersion of SEDDS under gastric conditions by inhibiting the formation of crystal nucleus and the growth of crystals. HPMC had evident effects on the rate of SEDDS lipolysis and benefited the distribution of drug molecules across into the aqueous phase and the decrease of drug sediment. The mechanisms were related to the formed network of HPMC and its viscosities and molecular weight. These results offered a reference for selecting appropriate type of HPMC as the precipitation inhibitor of supersaturatable SEDDS.
Caprylates ; chemistry ; Chemical Precipitation ; drug effects ; Crystallization ; Drug Delivery Systems ; methods ; Emulsifying Agents ; chemistry ; Emulsions ; Ethylene Glycols ; chemistry ; Glycerides ; chemistry ; Hypromellose Derivatives ; administration & dosage ; chemistry ; pharmacology ; Indomethacin ; administration & dosage ; chemistry ; Lipolysis ; drug effects ; Molecular Weight ; Polyethylene Glycols ; chemistry ; Viscosity

OBJECTIVETo improve the oral bioavailability of patchoulic alcohol in rats by using self-microemulsifying drug delivery systems (SMEDDS).

METHODPatchoulic alcohol was separated and purified from patchoulic oil, and the SMEDDSs including patchoulic alcohol or patchoulic oil were optimized by pseudo-ternary phase diagrams via central composite design-response surface methodology. Pharmacokinetics of both SMEDDSs and patchoulic alcohol itself in rats were investigated.

RESULTThe patchoulic alcohol SMEDDS (Cremophor EL-Tween 80-PEG 400-isopropyl myristate-patchoulic alcohol, 2:2:0.8:1.95:0.65) was considered as the optimized formulation. The mean drop size of the system was 30. 1 nm after diluted 100 folds in water. The average self-microemulsifying time was 142 s. Patchoulic alcohol SMEDDS and patchoulic oil SMEDDS showed no signficant difference in Tmax compared with patchoulic alcohol with around 60 minutes, while the AUCs of both SMEDDSs (2001 745.6 +/- 329 663.6) and (1594 005.6 +/- 280 150.3) microg x min x L(-1) were significantly higher than that of patchoulic alcohol (1 163 153.3 +/- 232 324.3) microg x min x L(-1).

CONCLUSIONSMEDDS can effectively improve the oral bioavailability of patchoulic alcohol in rats.

Administration, Oral ; Animals ; Biological Availability ; Chemistry, Pharmaceutical ; Drug Delivery Systems ; methods ; Drug Stability ; Emulsifying Agents ; chemistry ; Ethanol ; chemistry ; Female ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Self Administration ; Sesquiterpenes ; chemistry ; Solubility

OBJECTIVETo study the prescription and preparation of intravenous submicron emulsion of Oleum Cinnamomi oil of Miao nationality herbal.

METHODUsing the high speed blender mixed round the Oleum Cinnamomi oil with the soybean phospholipids and Pluronic F68 as emulsifier, then using the high pressure homogenizer made the intravenous submicron emulsion of the Oleum Cinnamomi oil and investigate its grain path and distributing.

RESULTHaving been done by using hydroextractor 4,500 r min(-1) 15 minutes the submicron emulsion grain path has well proportioned distribution.

CONCLUSIONThe preparation technology is simple and has good stability, so it can be used as a method to make the intravenous submicron emulsion of the Oleum Cinnamomi oil of Miao nationality herbal.

Cinnamomum ; chemistry ; Drug Compounding ; Emulsifying Agents ; chemistry ; Fat Emulsions, Intravenous ; chemistry ; Microscopy, Electron, Transmission ; Nanoparticles ; chemistry ; ultrastructure ; Particle Size ; Phospholipids ; chemistry ; isolation & purification ; Plant Oils ; chemistry ; isolation & purification ; Plants, Medicinal ; chemistry ; Poloxamer ; chemistry ; Soybeans ; chemistry

This paper report the development of a new dosage form - self-microemulsifying mouth dissolving films, which can improve the oral bioavailability of water insoluble drugs and have good compliance. A three factor, three-level Box-Behnken design was used for optimizing formulation, investigated the effect of amounts of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hypromellose on the weight, disintegration time, cumulative release of indomethacin after 2 min, microemulsified particle size and stretchability. Optimized self-microemulsifying mouth dissolving films could fast disintegrate in (17.09 +/- 0.72) s; obtain microemulsified particle size at (28.81 +/- 3.26) nm; and release in vitro at 2 min to (66.18 +/- 1.94)%. Self-microemulsifying mouth dissolving films with broad application prospects have good compliance, strong tensile and can be released rapidly in the mouth through fast self-microemulsifying.
Administration, Oral ; Biological Availability ; Cellulose ; analogs & derivatives ; chemistry ; Drug Compounding ; methods ; Drug Delivery Systems ; methods ; Emulsifying Agents ; chemistry ; Emulsions ; Hypromellose Derivatives ; Indomethacin ; administration & dosage ; Methylcellulose ; analogs & derivatives ; chemistry ; Particle Size ; Solubility ; Surface Properties ; Tensile Strength

The main purpose of this work is to prepare self-emulsifying drug delivery system (SEDDS) of a poorly water soluble drug, puerarin. Solubility of puerarin was determined in various oils and surfactants. Oleic acid and Tween 80 provided higher solubility. Addition of propylene glycol as cosurfactant improved solubility of puerarin and the spontaneity of self-emulsification. A series of mixtures comprising oleic acid, propylene glycol and Tween 80 were prepared and their self-emulsifying properties were studied. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and particle sizes of the resultant emulsions were determined using a laser diffraction sizer. The pharmacokinetic behaviors of three different SEDDS formulations (F2, F3, F4) were investigated in Beagle dogs. The bioavailability was compared using the pharmacokinetic parameters, peak plasma concentration (C(max)), time to reach peak plasma concentration (T(max)) and total area under the plasma concentration-time curve (AUC(0-t)). AUC(0-t) was significantly higher in formulation F2 group (5.201 +/- 0.511) ng x mL(-1) x h and formulation F3 group (5.174 +/- 0.498) ng x mL (-1) x h than that in formulation F4 group (3.013 +/- 0.623) ng x mL(-1) x h. Also, C(max) was significantly higher in formulation F2 group (1.524 +/- 0.125) ng x mL(-1) and formulation F3 group (1.513 +/- 0.157) ng x mL(-1) than that in formulation F4 group (0.939 +/- 0.089) ng x mL(-1). Further analysis of the data showed a statistically significant difference between F2 and F4 (P < 0.01) as well as F3 and F4 (P < 0.01) with regard to the values of AUC(0-infinity) and C(max) for three SEDDS formulations, but not between those of F2 and F3 (P > 0.05). From these studies, the SEDDS formulation containing oleic acid (17.5%), Tween 80 (34.5%) and propylene glycol (34.5%) (w/w) was selected as an optimized SEDDS formulation of puerarin. The data suggest the potential use of SEDDS to improve oral absorption of puerarin.
Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Dogs ; Drug Compounding ; Drug Delivery Systems ; methods ; Emulsifying Agents ; chemistry ; Emulsions ; Isoflavones ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Male ; Oleic Acid ; chemistry ; Particle Size ; Polysorbates ; chemistry ; Propylene Glycols ; chemistry ; Solubility ; Surface-Active Agents ; chemistry ; Vasodilator Agents ; administration & dosage ; blood ; chemistry ; pharmacokinetics