Microemulsion Region Research Articles

Microemulsion composed of combination of skin beneficial oils as vehicle: Development of resveratrol-loaded microemulsion based formulations for skin care applications

Microemulsion can be a potential delivery vehicle to deliver skin care actives to deep skin layer for chronic skin care benefits. On top of skin care active, microemulsion vehicle composed of multiple skin beneficial oils can deliver additional skin care efficacies. In this study, microemulsions were developed using combinations of two skin beneficial oils, tea tree oil and medium chain triglyceride instead of single oil. For that, pseudo ternary phase diagrams were constructed on these oil combinations at different ratios of surfactant/co-surfactants. Ratio of oils and surfactant/co-surfactant combinations exhibited significant impact on the microemulsion region. A few compositions were selected from the single phase microemulsion regions of these phase diagrams for the preparation of resveratrol-loaded microemulsion and microemulsion gel formulations. The particle size of the resveratrol-loaded microemulsions were <50 nm. Cryogenic scanning electron microscope image clearly showed nano-droplets dispersed in continuous phase. Both physical and chemical stability of the formulations varied depending on their compositions, such as surfactant/co-surfactant combination and % total oil. The presence of chelating agent and anti-oxidant was also crucial to stabilize the formulations. The selected formulations demonstrated good physicochemical stability at 5 °C, 25 °C, and 40 °C/75 % RH (relative humidity) stability conditions. The results further showed that the % total oil and surfactant phase composition had huge influence on resveratrol release and skin permeation patterns from the microemulsion gels. In vitro skin permeation result indicated that the microemulsion gels can help resveratrol penetration into deep skin layer. Therefore, the developed resveratrol-loaded microemulsion gels can be utilized as skin care product with multiple skin care benefits.

In vitro and in vivo studies of micro-depots using tailored microemulsion for sustained local anaesthesia

In clinical practice, lidocaine is used as local anesthetic for the management of post-operative pain. The commercial formulation including gels, injections and ointments showed short duration of action (1 to 2 h). In this paper, the efforts have being made to develop tailored lidocaine-microemulsion (o/w), which on penetration in the skin layer cause micro-depots formation due to destabilization of the microemulsion system. To identify the microemulsion region, pseudo ternary diagrams were constructed using Capmul MCM as oil, Pluronic F68 as tri-block surfactant, polyethylene glycol 200 as co-surfactant at 1:4 and 1:6 ratios (S:Co-S). The selected 5%w/v lidocaine loaded microemulsion [Ld-ME-2(1:4)] was stable in thermodynamic test and during shelf life period (3 months). In ex vivo permeability study, the lidocaine release from Ld-ME-2(1:4) microemulsion was sustained in comparison to the marketed lidocaine ointment. The skin irritation study confirmed the safety of lidocaine loaded microemulsion. Tail flick test showed improved and sustain local anaesthetic effect in comparison to the market ointment. The improved efficacy of microemulsion system, was due to high penetration in the skin layer due to local precipitation of lidocaine from microemulsion. The findings suggest that the tailored microemulsion could be a potential strategy to prolong the local anaesthesia.

LIPID BASED SOLID SELF-EMULSIFYING DELIVERY SYSTEM OF PITAVASTATIN CALCIUM: DEVELOPMENT AND CHARACTERIZATION

Solid self-emulsifying delivery system containing pitavastatin calcium was developed using oil and hydrophilic surfactants. Pitavastatin calcium has low solubility and low bioavailability; hence, it was meaningful to improve solubility and dissolution properties by using suitable formulation component and process. Based on preliminary study, oleic acid, Tween 20 and PEG 400 were utilized for development of self-emulsifying system. Microemulsion region was identified by pseudo-ternary phase diagrams. The liquid system: adsorbent (Aerosil 200) at a ratio of 2:1 was employed for spray drying. The system was evaluated for emulsification time, percent drug content, in-vitro dissolution. The other analytical techniques used for characterization were FTIR, DSC, SEM, particle size, zeta potential and XRD. The optimized formulation had particle size of 172.2 nm and the drug content found was 96.38%. It also had shown 95.98% drug release at the end of 1 hr which was more when compared to pure drug. It was observed that increase in surfactant concentration decreases dispersion time and particle size with concomitant increase in amount of drug released. The XRD diffractogram confirmed the conversion of drug from crystalline to amorphous form. The spray dried particles had smoother surface. The DSC thermogram showed no melting endotherm in the system indicating well dispersed drug with amorphous nature.

Formulation and Evaluation of Self-emulsifying Drug Delivery System of Poorly Soluble Drug using Varying Chain Surfactants

In the present study, the aim was to formulate self-emulsifying drug delivery system of mefenamic acid. Two homologous surfactants of Tween series, Tween 20 and Tween 40 were used as surfactants. The two surfactants were used to formulate a self-emulsifying system of mefenamic acid using a common co-surfactant ethanol. The clear microemulsion regions obtained in phase diagram of Tween 40 was larger than Tween 20; which indicates that Tween 40 has good emulsifying ability. Tween 20 has a hydrophobic chain length of 12 carbons, whereas Tween 40 has a hydrophobic chain length of 16 carbons, so increment in carbon chain length provides good self-emulsifying ability due to better shielding of the hydrophobic core. This inference is further consolidated after formulating six different formulations using the two surfactants and subjecting them to various evaluation parameters. The formulations containing Tween 40 were superior in all the evaluation parameters, including particle size, zeta potential, and drug release rate. The optimized formulation’s particle size, zeta potential, and drug release rate (in 60 minutes) were 187.20 nm, -22.2 mV, and 90.42%, respectively

Development and Characterization of Water-in-Oil Microemulsion for Transdermal Delivery of Eperisone Hydrochloride

Background: Eperisone hydrochloride possesses short biological half-life due to first pass metabolism resulting in low bioavailability and short duration of response with toxic effects, ultimately limits its utilization for treatment of muscle spasm. Objective: In view of this background, current study was designed for the development of Eperisone hydrochloride-loaded microemulsion and Eperisone hydrochloride-loaded microemulsion based cream for topical delivery and compared it with conventional cream. Methods: Firstly, water-in-oil microemulsion was prepared by spontaneous emulsification method. The concentration of components was found out from existence of microemulsion region by constructing pseudoternary phase diagram. The oil was selected on the basis of drug solubility effect on the drug release, whereas surfactant and cosurfactant were screened on the basis of their efficiency to form microemulsion region. The influence of components on microemulsion formation, drug release capacity, permeation was studied by differential scanning calorimetry, X-ray diffraction, in-vitro release and ex-vivo drug permeation studies respectively. By using microemulsion, the cream was prepared for proving optimum structure for topical application. Microemulsion was evaluated for droplet size, zeta potential, pH, viscosity and conductivity. Besides the cream was characterized for pH, rheology and stability. Permeation of EPE from microemulsion across the rat skin was evaluated and compared with conventional cream. Results: The microemulsion consisting Isopropyl Myristrate/Water/Span 80:Tween 80 (50/8/42% by weight) possessed droplet size of 95.77nm, zeta potential of −5.23 mV with 7.25 pH and conductivity near to zero (&lt;0.05mScm-1). Physical parameters of the cream were satisfactory, also 2.33-fold higher permeation and 1.57-fold higher release observed as compared to conventional cream. Conclusion: It can be concluded that Eperisone hydrochloride-loaded microemulsion and its cream is being effectively used for muscle spasticity by topical route.

The physics of microemulsions extracted from modeling balanced tensionless surfactant-loaded liquid–liquid interfaces

Microemulsions are explored using the self-consistent field approach. We consider a balanced model that features two solvents of similar size and a symmetric surfactant. Interaction parameter χ and surfactant concentration φs b complement the model definition. The phase diagram in χ-φs b coordinates is known to feature two lines of critical points, the Scott and Leibler lines. Only upon imposing a finite distance between the interfaces, we observe that the Scott line meets the Leibler line. We refer to this as a Lifshitz point (LP) for real systems. We add regions that are relevant for microemulsions to this phase diagram by considering the saturation line, which connects (χ, φs b)-points for which the interface becomes tensionless. Crossing this line implies a first-order phase transition as internal interfaces develop, characteristic for one-phase microemulsions. The saturation line ends at the so-called microemulsion point (MP). The MP is shown to connect with the LP by a line of MP-like critical points, found by searching for a "MP" while the distance between interfaces is fixed. A pair of binodal lines that envelop the three-phase (Winsor III) microemulsion region is shown to connect to the MP. The cohesiveness of the middle phase in Winsor III is related to non-monotonic, inverse DLVO-type interaction curves between the surfactant-loaded tensionless interfaces. The mean and Gaussian bending modulus, relevant for the shape fluctuations and the topology of interfaces, respectively, are evaluated along the saturation line. Near the MP, both rigidities are positive and vanish in a power-law fashion with coefficient unity at the MP. Overseeing these results proves that the MP has a pivoting role in the physics of microemulsions.

The palm oil-based microemulsion: Fabrication, characterization and rheological properties

The conversion and utilization of agricultural biomass have shown great prospects in the development of new bio-based materials. In this work, we presented palm oil fractionations having different melting points (24 °C, 33 °C and 43 °C) to fabricate microemulsion (ME), aiming to broaden renewable biomass-based materials basestocks. The palm oil fractionations were used as the continuous phase to formulate W/O ME. According to pseudo-ternary phase diagrams, the largest ME regions were formed with Span80 as the surfactant when the ratio of palm oil (LMP, MMP and HMP) to composite surfactant phase were 6:4, 1:9 and 7:3, respectively. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) confirmed droplets size of synthesized ME were 150–500 nm. Differential scanning calorimetry (DSC) results demonstrated thermal stabilities of designed ME were markedly enhanced. Rheology results showed synthesized ME exhibited excellent ability in anti-shearing changing, which led to a potential application in biomass-based materials, especially in requiring high anti-shearing fields.

Properties and Phase Behavior of Water-in-Diesel Microemulsion Fuels Stabilized by Nonionic Surfactants in Combination with Aliphatic Alcohol

We investigate the properties and phase behavior of the water–diesel fuel–Neonol AF 9-6/2-ethylhexanol system, which is regarded as a promising microemulsion fuel. A pseudoternary diagram of the system has been obtained. In the diesel fuel/water (DF/W) ratio ranging from 98:2 to 50:50 and the emulsifier concentration of 8–40 vol %, a region of microemulsions has been distinguished, generating particular interest as an alternative fuel. In the region under study, a reverse micellar phase L2 has existed predominantly. Fish-cut diagrams have been obtained for the DF/W ratios in the emulsifier concentration–temperature coordinates. An increase in the water fraction in microemulsions significantly has narrowed the range of their stability. The critical changes of microemulsion properties have been identified using the fish-cut diagrams. We have established the empirical relationship among the phase inversion temperature, the emulsifier concentration in the phase inversion point, and the water fraction in micro...

Self Microemulsifying Immediate Release Tablet of Azilsartan for Enhanced Dissolution

Azilsartan has solubility problem which leads to low dissolution and hence bioavailability, hence it is necessary to improve solubility of azilsartan. Objective of study was to develop self micro emulsifying tablet of azilsartan to enhance dissolution. Liquid self micro emulsifying drug delivery system (SMEDDS) was prepared using ethyl oleate, Tween 80 and Transcutol P as oil, surfactant and co-surfactant respectively. Microemulsion region was predicted by constructing a pseudo-ternary phase diagram containing a different proportion of oil, surfactant, and co-surfactant. Liquid SMEDDS was then converted to solid form (S-SMEDDS) by adsorption technique using Neusilin US2 as a solid carrier and evaluated for various pre-compression micromeritic properties. This S-SMEDDS were then compressed into immediate release tablet. Developed tablet of azilsartan were reconstituted and evaluated for % Transmittance, globule size, zeta potential. Tablets were also evaluated for post compression parameters, in-vitro dissolution study, DSC, XRD and FTIR. Reconstitution properties of self emulsifying tablet showed spontaneous micro emulsification with globule size 210 nm and-37 mV zeta potential. From results of in-vitro dissolution study, it was found that the release of azilsartan was significantly increased as compared with pure azilsartan. Study concluded that dissolution of azilsartan can be significantly improved by formulating it in to self emulsifying tablet for getting improved oral bioavailability.

OP-10拟三元体系微乳区域相图研究

OP-10拟三元体系微乳区域相图研究

Comparison of O/W and IL/W Microemulsion Systems as Potential Carriers of Sparingly Soluble Celecoxib Drug

Active pharmaceutical ingredients with poor solubility in water and some organic solvents are a challenge in the pharmaceutical industry. To overcome this limitation, microemulsion systems are a choice to increase the solubility of a sparingly soluble active ingredient. The purpose of this study is to introduce and compare two types of oil-in-water (O/W) and ionic liquid-in-water (IL/W) microemulsions, which were formulated to increase the solubility of celecoxib as an active pharmaceutical ingredient. The proposed formulations are composed of the same nonionic surfactant/co-surfactant of Tween-80/transcutol®P, and different oil phases of isopropyl myristate, [BMIM][PF6] and [OMIM][PF6]. The pseudo-ternary phase diagrams for the microemulsion systems have been determined at a surfactant-to-co-surfactant mass ratio of 3:1 and 298.15 K. From the microemulsion region of the phase diagrams, four formulations was selected and their physico-chemical properties as density, viscosity, refractive index, electrical conductivity and surface tension were measured at 298.15 K. The solubilities of celecoxib in all selected formulations were also determined and compared. The results show considerable increases in solubility of the celecoxib in the ionic liquid-based microemulsion systems.

Development and application of an osthole microemulsion hydrogel for external drug evaluation

The aim of the study is to provide a new type of drug delivery, combining the advantages of a microemulsion with the transdermal administration of osthole. Appropriate oil phases, surfactants, and cosurfactants were screened by their solubility, transmittance, etc. The appropriate microemulsion ratio formula was selected by measuring the area of the formed microemulsion region from the pseudoternary phase diagram among the different proportions. After measuring the pH, zeta potential, particle size, etc., a 2% osthole drug-containing microemulsion was prepared, and transdermal experiments were performed using a Franz cell. To select a microemulsion formula with high stability and a high skin transmittance rate, 65% distilled water (w/w) was embedded into the microemulsion (7% IPM (w/w), 14% Tween 80 (w/w) and 14% Labrasol (w/w)), and the microemulsion gel was made with different proportions of carbomer. The structure, water content and molecular stability of the microemulsion gels were measured by TEM and DSC. Transdermal experiments were then performed using Franz cells, and these microemulsion gels were applied to determine the subcutaneous residual amounts and optimal skin penetration microemulsion formulations. Thereby, the best microemulsion gel formulation was selected.

Oil-Induced Viscoelasticity in Micellar Solutions of Alkoxy Sulfate.

Rheological properties of the solution of an extended surfactant, sodium alkoxy sulfate (C8-(PO)4-(EO)1-SO4Na), are investigated as a function of the presence of various paraffinic oils over a range of salt conditions in the Winsor III microemulsion region at oil fractions where the microemulsion is "oil-starved". The addition of as small as 3 vol % alkane to 2 wt % surfactant solutions at salt concentrations where the oil-water interfacial tension is minimized induces a sudden shift in the rheological behavior. The solution viscosity increases by 5 orders of magnitude, with solid-like behaviors (G' > G″) being observed in the entire frequency region investigated (0.01-100 rad/s). Commonly, in the cases where wormlike micelles are present in the solution, alkanes are believed to be solubilized in the core of micelles, leading to a radial growth of the cylindrical part of the wormlike micelle, resulting in a drop of end-cap energy (EC) and micelle length and a reduction in viscosity. In this study, however, the addition of oil causes the formation of wormlike micelles. The viscosity of solubilized-oil samples does, however, decrease with an increase in incorporated oil volume. We hypothesize that this "abnormal oleo-responsive" viscoelastic behavior is related to a spacer of intermediate hydrophilicity, that is, polypropylene oxide (PO) segment of the alkoxy sulfate, being inserted between the hydrophobic tail and hydrophilic head (the ethoxylated sulfate segment) of the extended surfactant. The addition of a small amount of oil likely extends the PO moiety and increases the tail length of the surfactant in the aggregates as well as reducing the headgroup size, driving the formation of wormlike micelles from a solution that initially had a viscosity consistent with the absence of such structures.

The Influence of Surfactant/Co-Surfactant Hydrophilic-Lipophilic Balance on the Formation of Limonene-Based Microemulsion as Vitamin C Carrier

This research was conducted to produce a limonene-based microemulsion system as vitamin C carrier. The microemulsion was produced using limonene as the oil phase, tween20 and tween80 as surfactants while propylene glycol, polyethylene glycol 400 and glycerol as co-surfactants. Pseudo-ternary phase diagrams were constructed to determine the microemulsion area by using the water titration method at 25°C. The effect of hydrophilic-lipophilic balance (HLB) value of the mixture of S/CoS on the formation of limonene-based microemulsion was studied. The HLB value calculated for the mixture of tween20/propylene glycol in the different ratio was between 10.1 and 13.4. From the experiment, the preparation of limonene-based microemulsion system with tween20/propylene glycol was able to provide large and high stability of microemulsion region on ternary phase diagram (23.6%) while higher HLB value resulted in larger microemulsion area in ternary phase diagrams. The sole formulation with propylene glycol was further selected to carry out the physicochemical characterization of system’s stability, particle size and electrical conductivity. All microemulsion systems showed good stability for four weeks at temperature of 4, 25 and 40°C without any phase change and separation. Particle size characterization results elucidated that all microemulsion systems consisted particle size between 20 and 100 nm. The study of electrical conductivity showed that water-in-oil microemulsion was formed from 5-45% wt. of water whereas bicontinuous microemulsion was formed from 50-90% wt. of water content. Overall, the result showed that microemulsion tween20/propylene glycol/limonene/water was potential as a carrier system of vitamin C.

Preparation of Peppermint Oil-Based Nanodevices Loaded with Paclitaxel: Cytotoxic and Apoptosis Studies in HeLa Cells.

In this work, several normal, oil-in-water (o/w) microemulsions (MEs) were prepared using peppermint essential oil, jojoba oil, trans-anethole, and vitamin E as oil phases to test their capacity to load paclitaxel (PTX). Initially, pseudo-ternary partial phase diagrams were constructed in order to find the normal microemulsion region using d-α-tocopherol polyethylene glycol 1000 succinate (TPGS-1000) as surfactant and isobutanol (iso-BuOH) as co-surfactant. Selected ME formulations were loaded with PTX reaching concentrations of 0.6mgmL-1 for the peppermint oil and trans-anethole MEs, while for the vitamin E and jojoba oil MEs, the maximum concentration was 0.3mgmL-1. The PTX-loaded MEs were stable according to the results of heating-cooling cycles and mechanical force (centrifugation) test. Particularly, drug release profile for the PTX-loaded peppermint oil ME (MEPP) showed that ∼ 90% of drug was released in the first 48h. Also, MEPP formulation showed 70% and 90% viability reduction on human cervical cancer (HeLa) cells after 24 and 48h of exposure, respectively. In addition, HeLa cell apoptosis was confirmed by measuring caspase activity and DNA fragmentation. Results showed that the MEPP sample presented a major pro-apoptotic capability by comparing with the unloaded PTX ME sample.

Lecithin Microemulsion Lipogels Versus Conventional Gels for Skin Targeting of Terconazole: In Vitro, Ex Vivo, and In Vivo Investigation

Topical treatment of fungal infections has several superiorities over oral treatment. However, the greatest challenge for dermal delivery is the stratum corneum which is considered an effective barrier for penetration of most antifungal drugs into deeper skin layers. Terconazole (Tr), which is the first marketed triazole antifungal, was reported to be one of the most active azoles against vaginal candidiasis. Nevertheless, our work group is the first to investigate the potential of Tr in the treatment of skin mycosis via integration into lecithin microemulsion-based lipogels (LMBGs). The microemulsion regions of the investigated systems were detected through ternary phase diagrams. The in vitro characterization studies revealed promising physicochemical merits for the selected LMBGs as well as satisfactory in vitro antifungal activity. The current research work was endeavored to investigate the potential of such novel Tr-loaded LMBGs in comparison with conventional gels. Ex vivo permeation and retention studies in addition to in vivo deposition study showed a significant improvement in the permeability of Tr through animal skin from LMBGs compared to other conventional gels. Furthermore, the optimized microemulsion lipogel proved to be safe and a nonirritant to experimental animals through the acute sensitivity study and histological skin examination. Overall, lecithin-based microemulsion lipogels of different composition confirmed their potential as interesting nanocarriers for skin delivery of terconazole compared to current therapy.

Coconut Oil Based Microemulsion Formulations for Hair Care Product Application

Coconut oil in microemulsion is a better option than conventional practice since it can incorporate bioactive ingredients with a stable control release property, especially for hair care products. This work aims to develop microemulsion systems based on coconut oil with the addition of Tween 20, Tween 40, and Tween 80 as non-ionic surfactants (S), and propylene glycol as a co-surfactant (CoS). The determination of microemulsion regions in the ternary phase diagram was carried out by water titration method and the properties of the microemulsion were analysed. Based on the results, the microemulsion system of coconut oil with Tween 80 produced the largest microemulsion region compared to Tween 40 and Tween 20. Microemulsion systems of coconut oil/Tween 80 with the addition of propylene glycol with the ratio of S/CoS at Km = 3:1, 2:1, and 1:1 resulted in a decrement of microemulsion regions compared to using merely Tween 80. The microemulsion system of coconut oil/Tween 80/water at the ratio of oil: surfactant = 1:9 was chosen for further characterisations. Viscosity and electrical conductivity studies showed that the microemulsion system was water-in-oil (w/o) type as there was no phase transition to bicontinuous (BC) or oil-in-water (o/w) type due to low percentage of water content. Stability studies showed that the microemulsion system remained clear and stable at 25 and 40°C upon one-month storage except at 4°C where the system became cloudy and turbid. For particle size analysis, the microemulsion system possessed particle size less than 100 nm.

Esterification of Oleic Acid with n-Octanol in Three-Phase Microemulsions

AbstractIn the presence of dodecylbenzene sulfonic acid (DBSA), a part of the phase diagram of water, oleic acid, and n-octanol was constructed as a function of the temperaure dependent from DBSA-concentration. The liquid three-phases microemulsion region in the phase diagram was efficient for the esterification of oleic acid and n-octanol. The results exhibit that the shift of phase boundary contributed to product separation and catalyst recycling.

Experimental study on the viscosity reduction of heavy oil by using of a new type of micro-emulsion

In order to achieve an efficient exploitation of heavy oil reservoirs, a new type of micro-emulsion is prepared with alkyl phenoxy carboxylic acid, co-surfactant (alcohols), diesel oil and water to efficiently reduce the viscosity of heavy oil. With the increase of the chain length of the co-surfactant in a certain range, a larger area of the micro-emulsion region can be obtained. Besides, a clear and transparent micro-emulsion can be obtained when the volume ratio of water-diesel oil is from 8:2 to 5:5. Under the action of micro-emulsion, the viscosity reduction rate of heavy oil reaches over 90% and the electrical conductivity can be greatly increased when the addition of the mass concentration of micro-emulsion is 1%. The results can provide a technical basis for the efficient exploitation of heavy oil reservoirs.

Design Development and Evaluation of Agomelatine Microemulsion for Intranasal Delivery

The purpose of this study was to develop and optimize microemulsion containing agomelatine for intranasal delivery. Agomelatine, an antidepressant drug, has absolute bioavailability of only 5% due to high first pass metabolism. Agomelatine microemulsion and were prepared by titration method. Ternary phase diagram gave the microemulsion region and the concentration of oil; Smix and water were selected from ternary phase diagram. Based on solubility study, oleic acid, tween 80 and propylene glycol were selected as oil, surfactant and co surfactant respectively. Microemulsions were prepared using water titration method. 1:1% v/v ratio (Tween 80: Propylene glycol) was selected for formulation development. The prepared microemulsions were optimized optical transparency, viscosity measurement, phase separation, determination of pH, measurement of globule size, measurement of zeta potential, drug content, In vitro diffusion study, stability studies. The optimized batch was further characterized for optical transparency, viscosity measurement, phase separation, determination of pH, measurement of globule size, measurement of zeta potential, drug content, In vitro diffusion study, stability studies.&#x0D; Keywords: Depression, Intranasal, Microemulsions, Agomelatine