Oil Phase Ratio Research Articles

In Vitro and In Vivo Drug Release from a Novel In Situ Forming Drug Delivery System

The objective of this work was to investigate the influence of various preparation and formulation parameters on the in vitro and in vivo release of bupivacaine hydrochloride from an injectable in situ forming microparticle system (ISM). The in vitro drug release of ISM was investigated as a function of various formulation and process parameters and was compared to the drug release from in situ forming implants and conventional microparticles. In vivo studies were carried out in male Sprague-Dawley rats. Upon contact with an aqueous medium, the internal polymer phase of the ISM system solidified and formed microparticles. The initial drug release from ISM systems was reduced with decreasing polymer phase/external oil phase ratio. An advantage of the ISM system compared to in situ implant systems was the significantly reduced burst effect, resulting in drug release profiles comparable to microparticles prepared by conventional methods. The in vivo drug release studies were in good agreement with the in vitro drug release. With the ISM system, the analgesic effect of the bupivacaine hydrochloride was prolonged when compared to the injection of a drug solution or drug-polymer solution. ISM are an attractive alternative for parenteral drug delivery systems.

Incorporation of water-soluble drugs in PLGA microspheres

Poly(lactide- co-glycolide) (PLGA) microspheres containing blue dextran, as a model of water-soluble drugs, were prepared from w 1/o/w 2 emulsions by using a microhomogenizer and a solvent evaporation method. Effects of preparation conditions, such as, concentration of poly(vinyl alcohol) (PVA) in w 2 phase, viscosity of inner soluble water phase, volume ratio of oil phase to w 1 phase in primary emulsion, PLGA concentration in oil phase, and molecular weight or composition of PLGA, upon the properties of PLGA microspheres containing water-soluble drugs were examined. Concentration of poly(vinyl alcohol) (PVA), the dispersant dissolved in w 2 phase of secondary emulsion did not show any effects on the final particle size. On the other hand, volume ratio of oil phase to water one in primary emulsion affected the final particle size, which seemed to be related to the local PLGA concentration in w 1/o emulsions. That is, the particle size increased as the volume ratio of w 1 phase against oil phase, w 1/o (v/v), increased. The loading efficiency, however, was not affected by the volume ratio of w 1/o (v/v), but affected by blue dextran concentration in w 1 phase. Higher loading efficiency was observed in PLGA microspheres prepared from w 1 phase containing lower concentration of blue dextran. Blue dextran solution (inner water phase) with the lower viscosity may result in the lower leakage ratio of blue dextran during the preparation procedure. Increases in concentration and molecular weight of PLGA made particle size larger.

A novel in situ forming drug delivery system for controlled parenteral drug delivery

The objective of this study was to investigate the in vitro drug (diltiazem hydrochloride and buserelin acetate) release from different in situ forming biodegradable drug delivery systems, namely polymer solutions ( in situ implants) and in situ microparticle (ISM) systems. The drug release from ISM systems [poly( d, l-lactide) (PLA) or poly( d, l-lactide- co-glycolide) (PLGA)-solution dispersed into an external oil phase] was investigated as a function of the type of solvent and polymer, polymer concentration and internal polymer phase:external oil phase ratio and was compared to the drug release from in situ implant systems and microparticles prepared by conventional methods (solvent evaporation or film grinding). Upon contact with the release medium, the internal polymer phase of the ISM system solidified and formed microparticles. The initial drug release from ISM systems decreased with increasing polymer concentration and decreasing polymer phase:external oil phase ratio. The type of biocompatible solvent also affected the drug release. It decreased in the rank order DMSO > NMP > 2-pyrrolidone. In contrast to the release of the low molecular weight diltiazem hydrochloride, the peptide release (buserelin acetate) was strongly dependent on the polymer degradation/erosion. One advantage of the ISM system when compared to in situ implant systems was the significantly reduced burst effect because of the presence of an external oil phase. ISM systems resulted in drug release profiles comparable to the drug release of microparticles prepared by the solvent evaporation method. Therefore, the ISM systems are an attractive alternative to existing complicated microencapsulation methods.

Catastrophic phase inversion of abnormal emulsions in the vicinity of the locus of transitional inversion

This paper deals with the phase behaviour of model abnormal emulsions of cyclohexane/water/polyethoxylated surfactant in the vicinity of the locus of transitional inversion (optimum formulation). Abnormal emulsions are formed under dynamic conditions if the phase containing the soluble surfactant becomes the dispersed phase. Phase maps have been suggested in the literature that define the boundaries of emulsion morphologies. On these maps, only one transformation can be observed for any formulation scan. Furthermore, the morphology of emulsions in the vicinity of the locus of transitional inversion is rather vague. One might assume that by changing the HLB of the surfactant used in an abnormal emulsion to favour the continuous phase, that abnormal emulsion will gradually transform to a normal emulsion of the same type. A new experimental procedure was adopted in which emulsification was started with abnormal emulsions. To transform the abnormal emulsions to the normal emulsion of the same type, they were exposed to variations in temperature, the surfactant HLB, or water–oil phase ratio. As the optimum formulation was approached, the abnormal emulsions became so unstable that could not exist anymore in the un-favoured morphology and inverted to the normal emulsion of the opposite type. Further variation in the formulation along the route led to a transitional inversion to the normal emulsion of the original type. The result indicates an important finding that the transformation of abnormal emulsions to normal ones of the same type occurred via two successive inversions of catastrophic and transitional nature. It appears that the boundaries of catastrophic inversion correspond to the emulsions with the finest drop size. A modification to the phase behaviour maps, to include the locus of catastrophic phase inversion in the vicinity of the transitional inversion, was thus suggested.

Study on treatment of wastewater containing nitrophenol compounds by liquid membrane process

The research on treatment of wastewater containing nitrophenols was carried out by liquid membrane process. The various parameters were selected for nitrophenols concentration 1050 mg/l in wastewater, such as the surfactant concentration in oil phase 2%, the NaOH concentration in the internal water phase 2%, the ratio of oil phase to internal water phase 2, the pH of external water phase 2 and the ratio of external water phase to emulsion phase 3. The results indicate that the total nitrophenols in influent can be reduced from 1050 to <1 mg/l and from 6700 to <2.2 mg/l via one-stage liquid membrane process. The removal rate of total nitrophenols in wastewater was >99.9%, and the nitrobenzene and COD cr in wastewater were treated at same time also.

Myotoxicity studies of injectable biodegradable in-situ forming drug delivery systems

The objective of the study was to investigate the potential in-vitro and in-vivo myotoxicity of different in-situ forming biodegradable drug delivery systems, namely in-situ Microparticle (ISM) systems and polymer solutions (in-situ implant systems). The acute myotoxicity was evaluated in-vitro using the isolated rodent skeletal muscle model by measuring the cumulative creatine kinase (CK) efflux. For the in-vivo study, following intramuscular injection (i.m.) into male Sprague Dawley rats, the area under the plasma CK-curve was used to evaluate muscle damage. The formulations included ISM-systems [a poly (lactide)-solvent phase dispersed into an external oil phase] and poly (lactide) solutions (in-situ implant systems). Phenytoin and normal saline served as positive and negative controls, respectively. Poly (lactide) in different solvents (in-situ implant systems) resulted in 14.4–24.3 times higher CK-values compared to normal saline, indicating a high myotoxic potential. With the ISM-system, the CK-release was significantly lower, decreased with a lower polymer phase: oil phase ratio, and approached the values of normal saline at a ratio of 1:4. Bupivacaine HCl- and Buserelin acetate- containing ISM-systems resulted in significantly lower CK-levels when compared to the corresponding drug formulation in normal saline. The in-vivo studies confirmed the in-vitro data and showed good muscle compatibility of the ISM-systems.

Effect of preparation conditions on morphology and release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion method

We have investigated the key parameters to fabricate PDLLA (Poly( dl-lactic acid)), PDLLGA (Poly( dl-lactic-co-glycolic acid) 65 : 35 and blends of PDLLGA 65 : 35 and PEG (Poly(ethylene glycol)) microspheres containing bovine serum albumin (BSA) as a model protein using the double-emulsion (water-in-oil-in-water) solvent extraction/evaporation method. The release profiles of microspheres were investigated at 22°C in order to develop controlled release devices for marine fishes in tropical area. Various factors that influence the size of microspheres, encapsulation efficiency, initial release, morphology and release profiles of microspheres, and BSA distribution within microspheres have been investigated. These factors include preparation temperature, solvent removal rate, volume ratio of oil phase to internal water phase, and polymer concentration. Microspheres fabricated at a low volume ratio of oil phase to internal water phase and a low polymer concentration tend to have a large surface area, a low bulk density, resulting in a high initial burst and a fast release of BSA. Fabrication temperature heavily affects solvent extraction/evaporation and mechanism of phase-inversion. The microspheres fabricated at 4 and 38°C yield the highest encapsulation efficiency (52.0–48.0%) and lowest initial BSA release (18.8–20.0%), while microspheres produced at 22°C have the lowest encapsulation efficiency and highest initial burst. This interesting phenomenon is due to the fact that different phase-inversion paths occur when preparation temperature varies. Nucleation growth and spinodal decomposition dominate the skin formation at low preparation temperatures, while evaporation-driven skin formation takes place at high preparation temperatures. The relationship between the release profile and the rate of continuous water-phase addition is extremely complicated. Slow demixing dominates the interface skin formation at low continuous water-phase addition rates and results in fine porous skin structure, while rapid demixing dominates at high continuous water-phase addition rates and also leads to microspheres with a porous skin. Thus both have high initial bursts and fast release rates. A continuous water-phase addition of 3 ml/min may yield the microspheres having a low initial burst and a slow release rate.

Preparation of fine emulsified fat particles without glycerol for intravenous nutrition

A method of preparing fine emulsified fat particles without glycerol for intravenous nutrition was investigated. The factors assessed were the oil phase ratio, the glucose level of the aqueous phase and the temperature of high-pressure homogenization. The particle size decreased with an increase in the oil phase ratio and it went below 250 nm only in the emulsion with a 50% oil phase ratio. The weight-weighted particle size (d w)/number-weighted particle size (d n) value reflected the particle size distribution. The emulsion with a 50% oil phase ratio had a very narrow distribution of particle sizes and the d w/d n value was below 1.1. With the use of glucose solutions for the aqueous phase, smaller particle sizes and narrower distributions were obtained with increasing glucose concentrations. The controlled temperature of 50°C was appropriate for high-pressure homogenization, producing particles below 160 nm. The rate of the layer separation was a function of particle size. The particle sizes below 180 nm can be expected to suppress the separation of the formulation which consisted of 10.0% soybean oil, 1.2% phospholipids and 5.0% glucose. The stability studies were conducted at 40°C for 3 months and the fat emulsion was stable during storage. These investigations contribute to the preparation of a new caloric source for peripheral parenteral nutrition.

Cadmium removal from aqueous solutions by an emulsion liquid membrane: The effect of resistance to mass transfer at the outer oil–water interface

The removal of cadmium ions from an aqueous solution by an emulsion liquid membrane system is demonstrated, and the parameters of the system are experimentally studied in order to optimize the process. The principal result of the present study is the experimentally based conclusion that the main resistance to mass transfer may lie at the outer oil–water interface. This is shown by demonstrating that the separation process is almost independent of the water to oil phase ratio of the inner emulsion, which controls the inner interfacial area for mass transfer as well as the effective thickness of the oil membrane.

Stability of vitamin A in oil‐in‐water‐in‐oil‐type multiple emulsions

AbstractThe stabilityof vitamin A was studied in thee different emulsions: oil‐in‐water (O/W), water‐in‐oil (W/O), and oil‐in‐water‐in‐oil (O/W/O). The stability of retinol (vitamin A alcohol) in the O/W/O emulsion was the highest among the thee types of emulsions; remaining percentages at 50°C after 4 wk in the O/W/O, W/O, and O/W emulsions were 56.9, 45.7, and 32.3, respectively. With increasing peroxide value of O/W and W/O emulsifiers, the remaining percentage of vitamin A palmitate and retinol in the emulsions decreased significantly, indicating that peroxides in the formulae accelerate the decomposition of vitamin A. Organophilic clay mineral (an oil gelling agent and a W/O emulsifier) also affected the stability of retinol; synthesized saponite was better than naturally occurring bentonite for retinol stability. The stability of retinol in the O/W/O emulsion increased with increasing inner oil phase ratio (φi), whereas in O/W it was unaffected by φi. Encapsulation percent of retinol in the O/W/O emulsion, the ratio of retinol in the inner oil phase to the total amount in the emulsion, increased with increasing φi. The remaining percent of retinol in the O/W/O emulsion was in excellent agreement with encapsulation percent, suggesting that retinol in the inner oil phase is more stable than that in the outer oil phase. Addition of antioxidants (tert‐butylhydroxytoluene, sodium ascorbate, and EDTA) to the O/W/O emulsion improved the stability of retinol up to 77.1% at 50°C after 4 wk. We conclude that the O/W/O emulsion is a useful formula to stabilize vitamin A.

Demulsification of water-in-oil emulsion by using porous glass membrane

The hydrophilic porous glass membranes were used to demulsify water-in-oil emulsion, and demulsification efficiency can reach more than 96.2%. Effects of pore size of the membrane, transmembrane pressure and volumetric ratio of oil phase to internal aqueous phase in the emulsion on demulsification were investigated. It was found that pore size of membrane and transmembrane pressure can significantly affect demulsification efficiency. The smaller the pore size of the membrane, the better the demulsification efficiency. However, smaller pore size of the membrane has to be exerted a greater transmembrane pressure in order to make internal aqueous phase enter the membrane pore. Correspondingly, effect of transmembrane pressure on permeation flux of the droplets was also studied. In addition, recovered-oil phase by the demulsification were reused five times to extract cadmium from simulated aqueous waste. The results indicated that the extracting efficiency could arrive at 96.5%.

Serologic Response of Chickens Vaccinated with Inactivated Preparations of Mycoplasma gallisepticum

SUMMARY Several lots of inactivated Mycoplasma gallisepticum (MG) vaccine were prepared from 1% suspensions of the R strain. Portions were inactivated with 0.1% beta-propiolactone at room temperature (24 C) for 3 hours, and other portions were agitated with 0.5% formalin at 37 C for 3 hours. Part of each lot was then further processed to provide oil-emulsion preparations with various ratios of aqueous phase to oil phase. Tween 80 was added to the aqueous phase of most vaccines, and Arlacel 80 was added to the oil phase before final blending. The resulting hemagglutination-inhibition (HI) titers decreased in magnitude and duration in the following order: aqueous phase to oil phase ratios of 1:2, 1:4, and 1:1 followed by 25% aluminum hydroxide and aqueous vaccines. There was little difference in HI response of young broiler and egg-laying-type chickens injected by either the intra-foot-pad or subcutaneous routes with 0.5-ml doses of vaccines inactivated by either formalin or beta-propiolactone. Less than 0.25 ml was inadequate, and more than 0.5 ml was not greatly better. Two doses 8 weeks apart produced higher HI titers over a longer period than did a single dose. All of the water-in-oil vaccine emulsions were stable for at least 60 days at 37 C. No visible tissue reactions were produced by any of the vaccines studied.

Combustion of Emulsified Hydrocarbon Fuels

This review firstly describes the recently published theoretical analyses and experimental studies on the single droplet combustion of emulsified hydrocarbon fuels, and the results of application to direct-injection type combustors such as large and small scale boilers and diesel engines from a view point of low pollution and energy saving. Secondly, the emulsified fuels having high internal oil phase ratio were evaluated from a standpoint of safety, with the experimental data about the pool ignition and combustion . It is explained based on the fact that the singular combustion characteristics involving secondary microatomization decrease NOx and smoke emission, by water gas reaction and heat-sink effect of water for liquid phase cracking in residual fuels, and contribute to maintaining or improving the overall thermal efficiency and to enhancement of the safety.

An Application of the Phase-inversion-temperature Method to the Emulsification of Cosmetics. I. Factors Affecting the Phase-inversion Temperature

Abstract Recently, the PIT (phase-inversion-temperature) system was originated and developed by Shinoda and his collaborators as a guide to surfactant selection. In order to apply the PIT system to the cosmetic field, the effects of various factors on the PIT have been reinvestigated using cosmetic materials. POE alkyl ethers, whose distribution of EO chain lengths is broad, are widely used in cosmetics. In such a case, the effect of the distribution of the EO chain lengths is important. When a surfactant with a distribution of EO chain lengths was used, the PIT was lowered by an increase in the concentration of the surfactant, but when a monodisperse surfactant without any distribution was used, the PIT scarcely varied with the concentration of the surfactant. In the case of the surfactant with a distribution of EO chain lengths, however, if the ratio of oil to surfactant was kept constant, the PIT scarcely varied with the ratio of oil phase to water phase. This relationship can be used in estimating the PIT in the case of the practical production of an emulsion.