Dry Emulsion Research Articles

Study on Turning of Ti-6Al-4V with Water Steam as Coolant and Lubricant in Green Machining

To achieve green cutting of titanium alloy Ti-6Al-4V with water steam cooling and lubricating, a 600-800w minitype generator is developed. Compared to dry and water-based emulsion, the using of water steam decreases the main cutting force and the cutting temperature respectively; enhances the machined surface appearance. And it can help to chip forming and breaking. Water steam application also improves Ti-6Al-4V machinability and prolongs the tool life. The excellent cooling and lubricating action of water steam could be summarized that water molecule has polarity, small diameter and high speed, can be easily and rapidly to proceed adsorption in the cutting zone. The results indicate that the using of water steam has the potential to attain the green cutting of titanium alloy.

Interactions and antioxidant stability of sesamol in dry-emulsions

Dry emulsions prepared from saccharose (SAC), Labrafil M 1944 CS, sesamol (SEOH), and hydro- xypropylmethylcellulose (HPMC) or sodium caseinate (SC) by grinding or dissolution, and different desiccation tech- niques (spray (SD)- or freeze (FD)-drying, or heating at 60 C) were investigated to determine possible interactions between mixture components. The goal of this study was to determine the best formulation which will regenerate per- fectly, after water dilution of dry emulsions, the initial liquid emulsion with the same characteristics that before drying. The morphological state of SAC and dry emulsions were determined by scanning electron microscopy analysis (SEM) analysis. Glass transition temperature, and melting (endo- thermic), decomposition (endothermic), oxidation (exo- thermic) peak temperatures and enthalpies were measured by differential scanning calorimetry (DSC). The antioxidant activity of emulsions was evaluated through their ability to reduce 1,1-diphenyl-2-picrylhydrazil (DPPH) free radical. SEM analysis showed that SD-prepared, SC-containing dry emulsions formed better spherical particles with smooth surface at about 5 lm diameter as compared to emulsion containing HPMC. These former emulsions also showed more thermal stability by DSC. The combined results of the three analytical techniques emphasized the importance of the dry emulsion process regarding the efficiency and the ther- mal stability of antioxidant substances. A specific physical and/or chemical combination (such as hydrogen bond) suf- ficiently stable, at about 150 C, could be suggested when the technique used for dry emulsion preparation was SD. After water dilution, this dry emulsion obtained from quaternary mixture: SAC, Labrafil, SEOH and SC, will regenerate the initial liquid emulsion with the same characteristics that before drying.

Formulation of Dry Emulsion for Topical Applications

Dry emulsions were investigated for their possible use in cosmetic and pharmaceutical fields and an extract of Vitis vinifera leaves was obtained and characterized in terms of quality and quantitative levels, which can be introduced in a selected dry emulsion formulation. Several pre-dry emulsions were prepared, six of which were chosen as a consequence of their satisfying physico-chemical and over-time stability characteristics. They were successively freeze-dried and reconstituted after optimising the reconstitution modalities and characterized by optical microscopy, granulometric and thermal analysis, FTIR analysis, rheology, and texture studies. The best formulation was chosen to introduce Vitis vinifera dry extract prepared by percolation: a fair increase in anthocians stability was noted over time in dry emulsions as compared with classic emulsions.

Utilisation of pectin coating to enhance spray-dry stability of pea protein-stabilised oil-in-water emulsions

In this study, development of pea ( Pisum sativum) protein stabilised dry and reconstituted emulsions is presented. Dry emulsions were prepared by spray-drying liquid emulsions in a laboratory spray-dryer. The effect of drying on the physical stability of oil-in-water emulsions containing pea protein-coated and pea protein/pectin-coated oil droplets has been studied. Oil-in-water emulsions (5 wt.% Miglyol 812 N, 0.25 wt.% pea protein, 11% maltodextrin, pH 2.4) were prepared that contained 0 (primary emulsion) or 0.2 wt.% pectin (secondary emulsion). The emulsions were then subjected to spray-drying and reconstitution (pH 2.4). The stability of the emulsions to dry processing was then analysed using oil droplet size, microstructure, Zeta potential, and creaming measurements. Obtained results showed that the secondary emulsions had better stability to droplet aggregation after drying than primary emulsions. To interpret these results, we propound that pectin, an anionic polysaccharide, formed a less charged protective layer around the protein interfacial film surrounding the oil droplets that improved their stability to spray-drying mainly by increasing steric effects.

Preparation, characterization and in vitro intestinal absorption of a dry emulsion formulation containing atorvastatin calcium

A redispersible dry emulsion (DE) formulation of atorvastatin calcium (AC) was developed to enhance the in vitro dissolution of AC, thereby increasing its gastrointestinal absorption. The spray-drying technology was used where Plurol Oleique CC 497 was chosen as the oil phase. Effects of carriers, surfactants, and homogenizers on the characteristics of DE containing AC were systematically investigated. The final formulation consisted of dextrin and Poloxamer 188 as carrier and surfactant, respectively, and was homogenized by a high pressure homogenizer before spray drying. The in vitro release of AC from the optimized DE was significantly higher than that of pure AC powder (76% vs. 30% at 24 hr). The in vitro intestinal absorption of AC from the DE formulation was 0.77 μg/cm2 at 2 hr, which was a 2.33-fold increase compared to the pure unformulated AC powder. These results suggest that the oral dry emulsion formulation could improve the intestinal absorption of AC.

Silica-lipid hybrid (SLH) microcapsules: A novel oral delivery system for poorly soluble drugs

A silica-lipid hybrid (SLH) microcapsule system for oral delivery of poorly water-soluble drugs is reported for the first time. For the model drug celecoxib (CEL), SLH microcapsules composed of medium-chain triglycerides, lecithin and silica nanoparticles; with an internal porous matrix structure, were shown to offer several physicochemical and biopharmaceutical advantages in comparison with unmodified drug, lipid emulsion, dry emulsion and the commercial product, Celebrex ®. DSC and XRD analyses confirmed non-crystalline CEL in SLH microcapsules and verified medium term physical stability. Dissolution under sink conditions revealed a 2- to 5-fold increase in dissolution efficiencies (%DE) and significantly reduced t 50% (≥ 50-fold) for CEL formulated as SLH microcapsules. Orally dosed in vivo studies in rats demonstrated superior pharmacokinetics for SLH microcapsules. Specifically, the fasted-state bioavailability ( F) was statistically higher ( p < 0.05) than for aqueous suspension, lipid solution, o/w emulsion and a maltodextrin-stabilised dry emulsion, and was greater than for Celebrex ®. SLHs showed the highest maximum plasma concentration ( C max) among all tested formulations ( p < 0.05). Linear correlations were observed between %DE and the pharmacokinetic parameters ( F and C max). It is postulated that SLH microcapsules improve CEL oral absorption via dissolution enhancement, potentially in conjunction with other unexplored mechanisms, hence offering the possibility of dose reduction for improved therapeutic efficacy and cost-effectiveness of poorly soluble drugs.

Redispersible, dry emulsion of lovastatin protects against intestinal metabolism and improves bioavailability1

To prepare a redispersible, dry emulsion (DE) and investigate whether it can improve intestinal stability and oral absorptive efficiency of the poorly water-soluble lovastatin (Lov). Phosal 53 MCT, Tween 80, and starch sodium octenyl succinate were employed as the oil phase, emulsifying agent, and matrix material, respectively. The redispersible, DE of Lov (Lov-DE) was prepared by spray drying the submicron emulsion of Lov. The characteristics of DE and the in vitro drug release were studied. The protective effects on the metabolism of Lov- DE and reference formulations, including the Lov suspension and the hydroxypropyl-beta-cyclodextrin (CD) complex were investigated in microsomes and the gut wall of male Sprague-Dawley (SD) rats. The bioavailability in SD rats was evaluated simultaneously. Lov-DE in distilled water was reconstituted compared with the submicron emulsion of Lov before spray drying, and remained almost unchanged after 3 months' storage at room temperature. Compared with the Lov suspension, the in vitro Lov dissolution of both the redispersible, DE and CD complex increased obviously. Compared with control formulations, the metabolism studies carried out in vitro and in vivo confirmed that the redispersible, DE presented remarkable protective effects as indicated by the decreased metabolism rate of Lov. Lov-DE showed a 1.83-fold and 1.44-fold higher the area under the curve(AUC0-8 h)of Lov compared with that of the Lov suspension and CD complex in SD rats, respectively. Lov-DE reduced the metabolism of Lov in the small intestine and improved its oral absorption in SD rats.

Physicochemical and pharmacokinetic characterization of water-soluble Coenzyme Q 10 formulations

Coenzyme Q 10 (CoQ 10) has been used as a drug for chronic heart failure. Furthermore, various biological effects of CoQ 10 have also been applied for food supplements and cosmetics. However, CoQ 10 was found to be poorly soluble in water, so that its bioavailability was low and variable depending on food intake. In the present investigation, a novel liquid (nano-emulsion, NE) and water-soluble powder formulations, including cyclodextrin–Q10 complex (CoQ 10–CD) and dry-emulsion (DE), were prepared. The physicochemical properties of each formulation were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), powder X-ray diffractometry (PXRD), and differential scanning calorimetry (DSC). In all powder formulations prepared, CoQ 10 existed mainly as an amorphous form as determined by PXRD and DSC, and each powder formulation exhibited high solubility and dispersibility in water resulting in the formation of a nano-sized emulsion (NE; 60 nm) and micron sized particles (DEs and CoQ 10–CD; 0.77–2.4 μm). The pharmacokinetic study of each dosage form, in comparison to a CoQ 10 crystal suspension, was also carried out in rats after a single oral dose. Although similar kinetic values were seen with T max of 1.5 and 1.7 h, respectively, for NE and crystalline CoQ 10, NE exhibited ca 1.7-fold higher AUC and C max than the crystalline CoQ 10.

Relative bioavailability of griseofulvin lyophilized dry emulsion tablet vs. immediate release tablet: A single-dose, randomized, open-label, six-period, crossover study in healthy adult volunteers in the fasted and fed states

The oral bioavailability of griseofulvin (GF) formulated as a fast disintegrating lyophilized dry emulsion (LDE) tablet was studied and compared to the commercially available immediate release (IR) tablet, as a reference, in both the fasted and fed states in nine healthy volunteers after a single oral dose (125 mg) in a crossover design. Furthermore the LDE tablets were ingested with and without water under both the fasted and fed states. In the fasted state, the rate of absorption was found to be significantly faster from LDE tablets, in the presence and absence of water, as shown by a higher C max (more than two times higher, p = 0.0001) and a shorter t max (by more than 3 h, p = 0.0001) compared to IR tablets. The extent of absorption, expressed as AUC, from LDE tablets in the presence and absence of water was 65% and 77% larger and statistically significantly different relative to the mean AUC from IR tablets ( p = 0.006). In the fed state, C max from LDE tablets ingested with and without water was found to be about 30% and 50% higher, respectively, than the immediate release tablets. A shorter t max was also shown whether LDE tablets were ingested with or without water in the fed state as compared to immediate release tablets. The mean AUC from LDE tablets under fed conditions in the presence of water was about 21% larger and was not statistically significantly different from AUC from immediate release tablets ( p = 0.517). When ingested without water, AUC from LDE tablets was about 43% larger and statistically significantly different relative to AUC from IR tablets ( p = 0.033). The mean AUC from the LDE tablet ingested with water under fed conditions relative to AUC from LDE tablet ingested without water was not statistically significantly different ( p = 0.454). Results show that the food effect of the high fat meal is very pronounced in case of the immediate release tablets, Fulvin, than in case of LDE tablets whether given with or without water.

In vitro and in vivo evaluation of a fast-disintegrating lyophilized dry emulsion tablet containing griseofulvin

Development of a fast-disintegrating lyophilized dry emulsion (LDE) tablet that enhanced the in vitro dissolution and in vivo absorption of griseofulvin (GF) is presented. The LDE tablets were prepared by freeze-drying o/w emulsions of GF, a drug for which bioavailability is known to be enhanced by fat co-administration. Oil-in-water emulsions were prepared using a gelatin solution (2%, w/v) as the water phase and medium chain triglycerides (Miglyol) or sesame oil as the oil phase. In addition, different emulsifiers were evaluated. The influence of formulation parameters on the disintegration and in vitro dissolution of GF from LDE tablets along with other tablet characteristics were investigated. A significant influence of the emulsifier type on the tablet disintegration time was seen ( p < 0.01). Results obtained from dissolution studies showed that LDE tablets of GF improved the dissolution rate of the drug compared to the plain drug. The extent of absorption of GF from a selected LDE tablet formulation as compared to an immediate release conventional tablet as reference after single oral dose (125 mg) administration was determined in four healthy subjects using a randomized crossover design. In this study, the rate of absorption of GF from LDE tablet was faster than that from the reference tablet and had significantly higher ( p = 0.02) peak plasma concentration (more than three times higher) and shortened time to C max by 4 h ( p = 0.014). The extent of absorption expressed by AUC was 85% larger as compared to the commercial tablet. Stability results, after 6 months storage of LDE tablets at 25 °C and 60% relative humidity, showed a slight increase in disintegration time and residual moisture content, while results from dissolution studies showed slightly slower initial drug release.

Effect of Cryoprotectant and Freeze-Drying Process on the Stability of W/O/W Emulsions

In order to protect a hydrophilic drug and to prolong its further delivery, the formulation of multiple emulsions could be worthy. However, the double emulsions are not stable, their structure can change, leading to the formation of a single emulsion as the destruction of the system, and the drug can release easily from the globules in liquid state. The freeze-drying technology could be used to produce dry emulsion, the powder form being much more stable. The aim of this work was to study the influence of a cryoprotectant and a freeze-drying process on the stability of W/O/W emulsions. Samples were frozen at two different freezing rate (ν f = 0.55°C/min and 1.25°C/min) and successively dried at two different sublimation temperature (T s = − 10°C and − 20°C). The particle size distributions were measured by granulometer and UV spectrophotometer was performed to investigate the leakage of internal constituent. The glass transition temperature (T g ) of the double emulsions was analyzed by DSC. The particle sizes became even smaller after freeze drying, except when κ-carrageenan is used as a cryoprotectant. In that case, the particles became aggregated after freeze drying, whatever the process conditions. The mean size is considerably reduced when the globules are diluted at low concentration in glucose and trehalose solution. When the concentration is increased, the size distribution is not significantly affected. The leakage of the internal aqueous phase to the external one during freeze drying was measured as an indicator of the structure stability. It is affected by the nature of the cryoprotectant and the conditions of the freeze-drying process. The leakage of the internal phase was smaller when cycle III (ν f = 1.25°C/min, T s = − 10°C) was processed. From our experiments, we suppose that the water transfer from the inner phase to the outer aqueous phase results in the diminution of the globules size in double emulsion. The T g of the double emulsions diluted with trehalose and glucose were determined at − 33.8°C and − 47.1°C. In contrast, the T g of double emulsion with κ-carrageenan and HES did not appear.

Preparation of redispersible dry emulsion using Eudragit E100 as both solid carrier and unique emulsifier

To improve the patient's compliance and the physical stability of liquid emulsion, a novel dry emulsion being able to reform the original O/W-emulsion by reconstitution in artificial gastric fluid is presented. Dry emulsions were prepared by spreading liquid O/W-emulsions on a flat glass, dried at the oven maintained at 40 °C and then triturated to powders with suitable particle size. When the dry emulsions were immersed into gastric fluid, stable emulsions were formed in 5 min. Here a sole excipient, high polymer, was applied as both solid carrier and unique emulsifier, and Zedoary turmeric oil (ZTO) was used as a model drug. In this study the effects of different kinds of high polymers on the liquid emulsion and on the dispersibility of the dry emulsions were investigated. Eudragit E100 exhibited the best emulsifying ability and the dry emulsion prepared with it shows the quickest release property. And the mean emulsion droplet sizes of the original emulsions and the reconstruction emulsions were <1 μm. Here the basic properties of the polymers, such as contact angle and relative viscosity, were also investigated. With this method it was easy to prepare redispersible dry emulsion from liquid oil content up to 45%.

Improvement of bioavailability and photostability of amlodipine using redispersible dry emulsion

To improve the bioavailability and photostability of poorly water-soluble and photosensitive amlodipine, dry emulsion (DE) was prepared by spray-drying the oil-in-water emulsion of amlodipine. Labrafil M 1944 CS and dextrin were employed as oil phase and matrix material, respectively. Dispersing DE in distilled water formed an emulsion with a mean droplet size 1.4-fold larger than that of the homogenized amlodipine emulsion before spray-drying (0.24 ± 0.30 μm versus 0.17 ± 0.02 μm). The mean droplet size of DE remained unchanged during 6-month storage at room temperature. 94.4% versus 33.1% of amlodipine remained intact after 24-h UV irradiation of amlodipine as DE formulation or as powder. These data suggest that DE formulation greatly improved the photostability of amlodipine, as well as increasing the physical stability of emulsion systems. In vitro release of DE was higher than that of amlodipine powder (66% versus 48% release at 60 min). Consequently, DE formulation resulted in 2.6- and 2.9-fold higher C max and AUC 0–24 h of amlodipine compared after oral administration of amlodipine powder in rats. Our data suggest that the DE may be a potential oral dosage form for amlodipine to improve its bioavailability.

An enteric-coated dry emulsion formulation for oral insulin delivery

A novel oral dosage formulation of insulin consisting of a surfactant, a vegetable oil, and a pH-responsive polymer has been developed. First, a solid-in-oil (S/O) suspension containing a surfactant–insulin complex was prepared. Solid-in-oil-in-water (S/O/W) emulsions were obtained by homogenizing the S/O suspension and the aqueous solution of hydroxypropylmethylcellulose phthalate (HPMCP). A microparticulate solid emulsion formulation was successfully prepared from the S/O/W emulsions by extruding them to an acidic aqueous solution, followed by lyophilization. The insulin release from the resultant dry emulsion responded to the change in external environment simulated by gastrointestinal conditions, suggesting that the new enteric-coated dry emulsion formulation is potentially applicable for the oral delivery of peptide and protein drugs.

In vivo evaluation of tablets and capsules containing spray-dried o/w-emulsions for oral delivery of poorly soluble drugs

It is recognised that poorly soluble drugs may show an increased oral bioavailability when incorporated in o/w-emulsions. Encapsulating the emulsion lipid droplets in hydroxypropyl methylcellulose (HPMC) by spray drying has been demonstrated to preserve an improved bioavailability releasing lipid droplets from the powder in vivo. However, the spray-dried powder is cohesive and bulky requiring additional processing to improve handling. This was resolved in previous work where a directly compressible dry emulsion formulation was described. The purpose of the present study is to investigate the oral bioavailability resulting from administration of a directly compressible dry emulsion as a tablet and compare it with a HPMC dry emulsion powder and a simple lipid solution. Four female Beagle dogs received a single dose of each formulation containing the same amount of medium-chain triglycerides (MCT) and a model drug, Lu 28-179. Cyclodextrin solutions administered orally and intravenously were used as references. The absolute bioavailability decreased in the order cyclodextrin solution (0.14), HPMC dry emulsion (0.11), technically improved dry emulsion (0.10) and MCT solution (0.06). The directly compressible dry emulsion tablets were concluded to be comparable to a HPMC dry emulsion powder in terms of bioavailability. The lack of statistically significant differences relative to a MCT solution was ascribed to a low and variable absolute oral bioavailability of the model drug.

エマルションの最前線 エマルションによるドラッグデリバリー

A new solid-in-oil-in-water (S/O/W) emulsion consisting of edible surfactants, an edible oil, and a water-soluble drug has been developed for oral administration of peptide/protein drugs. Insulin, which is a hydrophilic macromoleclule, was converted into a lipophilic complex using edible surfactants. As the resultant complex can be directly solubilized in the oil phase, surfactant-insulin complexes can be incorporated into the oil phase of oil-in-water emulsions, allowing the formulation of stable S/O/W emulsions. The capability of S/O/W emulsions in the control of blood glucose was investigated with diabetic model rats. The glucose level in the serum slowly decreased over several hours when the S/O/W emulsions were orally administered, while the aqueous solution of insulin (as the control) showed no significant effect on the blood glucose level. The hypoglycemic effect of surfactant-insulin complex incorporated into the S/O/W emulsions and the stable encapsulation of insulin into dry emulsion formulations will offer one way to oral delivery of biopharmaceuticals.

Fast-disintegration oral tablets having sustained release property

Fast-disintegrating (FD) tablets containing nicorandil-loaded dry emulsions were prepared and their controlled-release properties were examined and compared with the plain FD tablets (FD tablets without dry emulsions) and commercial tablets. The dry emulsions were prepared with myristyl alcohol and stearyl alcohol and their property was modified by mixing the ratio of the two alcohols. Disintegration time of the prepared FD tablets was sufficiently fast (i.e., 12 to 23 s). In vitro release of nicorandil from the FD tablets containing the dry emulsions was sustained over 6 h, while that from plain FD and commercial tablets was complete within 5 min. In vivo absorption of nicorandil from the tablets was evaluated by oral administration in beagle dogs. FD tablets containing dry emulsions showed a similar AUC, lower Cmax, and delayed Tmax compared to the plain FD and commercial tablets. These results suggest that the dry emulsion-loaded FD tablets can be utilized to improve the sustained-release property of active drugs.

Physical stability of redispersible dry emulsions containing amorphous sucrose

The objective of the present study was to estimate the stability of redispersible dry emulsions containing amorphous sucrose. Dry emulsions were prepared by spray drying liquid o/w-emulsions in a laboratory spray dryer. The effect of hydroxypropyl methylcellulose (HPMC) on the glass transition temperature T g of spray dried sucrose-HPMC mixtures, relative to the T g of amorphous sucrose, was investigated. For the sucrose-HPMC mixtures the values of T g followed the ideal Gordon-Taylor equation up to 30% HPMC. For dry emulsions containing 40% HPMC, 30% lipid and 30% sucrose, the T g was increased by 12°C relative to the T g of amorphous sucrose. The stability of the dry emulsions was investigated by a conventional stability study and by an enthalpy relaxation study. The measured enthalpy recovery of amorphous sucrose below T g was used to calculate molecular relaxation time parameters based on the Williams-Watts equation. The molecular mobility of amorphous sucrose at temperatures 50°C below T g was low and negligible with respect to the shelf life stability. It was concluded that the dry emulsions are physically stable with respect to the lifetime of a pharmaceutical product when stored in dry condition and at temperatures up to 28°C.

Preparation of redispersible dry emulsions by spray drying

Development of stable dry emulsions being able to reform the original o/w-emulsion by reconstitution in water is presented. Dry emulsions were prepared by spray drying liquid o/w-emulsions in a laboratory spray dryer. Three hydroxypropylmethylcellulose (HPMC) types were applied as solid carrier and emulsifier. The lipid phase was fractionated coconut oil. The ratio of solid carrier to lipid phase influenced the reconstitution properties. It was possible to prepare redispersible dry emulsions of a lipid content up to 40% dry powder mass. The different HPMC types had no noticeable effect on the reconstitution properties, but too viscous liquid o/w-emulsions were difficult to atomise. The type of rotary atomizer, or the rate of rotation did not affect the technical properties of the dry emulsions containing 40% lipid. It was concluded that low viscosity HPMC was a useful solid carrier. The dry emulsions remained physically stable for at least 6 months.

Technical optimisation of redispersible dry emulsions

Preparation of dry emulsions suitable for tablet processing was examined in this study. Liquid o/w-emulsions were spray dried in a laboratory spray dryer applying hydroxypropylmethylcellulose (HPMC) as a solid carrier and emulsifier. As the lipid phase, fractionated coconut oil was used. The ability of various excipients to increase the density of dry emulsions was investigated. Adding sucrose to the formulation, redispersible dry emulsions with higher density were obtained. The type of rotary atomizer did not affect the dry emulsions containing sucrose nor the rate of rotation of the atomizer applied in the spray drying process. By wet granulation, using ethanol as a binder, free-flowing and compactable dry emulsions were obtained and simultaneously the reconstitution properties were preserved. It was concluded that dry emulsions could be optimised for tablet processing by wet granulation. Tablets having a lipid content up to 20% had proper tablet properties.