Particle Size Of Microemulsion Research Articles

Development and Evaluation of Ceftazidime Loaded Microemulsion for Parenteral Drug Delivery System

The goal of this study was to develop a parenteral microemulsion formulation of Ceftazidime antibiotics. The ceftazidime sparingly soluble in organic solvent like ethanol, DMSO, and dimethyl formamide were determined. For biological experiment, organic solvent- free aqueous solutions of ceftazidime (hydrate) are prepared by directly dissolving the crystalline compound in aqueous buffer. The peudo ternary phase diagrams of oil, surfactant, cosurfactants (Butanol/ Isopropyl alcohol mixture) and water were constructed to identify boundaries for microemulsion existence. Ceftazidime microemulsion particle size, solution viscosity and conductivity were evaluated. The microemulsion stability and haemolytic activity were examined after dilution in 5% dextrose solution for injection to 1 mg/mL ceftazidime. In vitro haemolysis studies indicated that Ceftazidime microemulsions were well tolerated by erythrocytes. The novel microemulsion formulation of Ceftazidime was developed that is suitable for parenteral administration. This new formulation could potentially have less vehicle-associated side effects that current commercial formulation of Ceftazidime based on Cremophor® EL and isopropyl alcohol solution.

STATISTICAL OPTIMIZATION AND STABILITY STUDY OF QUERCETIN-LOADED MICROEMULSION

Objective: This research aims to develop a quercetin microemulsion system to improve the solubility of quercetin and to study the stability of the microemulsions.
 Methods: The microemulsion is prepared by water titration method using isopropyl myristate (oil), Tween 60®/Span 80® (3:2) (surfactant) and ethanol (co-surfactant). Two different aqueous phases, water or NaCl solution, were used to prepare microemulsions and the influence of each parameter was described. DPPH scavenging and anti-tyrosinase activity were performed along with chemical stability to evaluate the functional stability of microemulsions.
 Results: The influence of percentage of oil phase (variable A) on the solubility of quercetin was less significant than that of percentage of surfactant/co-surfactant (variable B). Compared to those prepared with water (variable C), the solubility of quercetin in microemulsions prepared with NaCl solution significantly increased. The ratio of the high level to low level for solubility of three variables was 1.135, 1.315 and 1.591 respectively. Increasing variable A and B led to an increase in the particle size of microemulsions from 120.08 nm to 188.38 nm and 48.18 nm to 260.28 nm, respectively. The influence of variable B was quite significant, while variable C has no significant effect on particle size. Quercetin microemulsions showed good chemical and functional stability when stored at 4 °C. Under other conditions, especially at 40 °C, the activity of the microemulsion is considerably reduced.
 Conclusion: The influence of different variables on the characteristics of microemulsions was complicated. Care must be taken in the composition and storage conditions of these formulations.

Evaluations of the Chuanqi Ophthalmic Microemulsion In Situ Gel on Dry Age‐Related Macular Degeneration Treatment

Age‐related macular degeneration (AMD) is the third largest eye disease. However, the eye has a variety of drug delivery barriers, which prevent the drug from reaching the lesions in the posterior segment of the eye, coupled with the pathogenesis of dry‐AMD; these lead to the lack of effective treatment drugs for dry‐AMD. Therefore, the developments of a suitable therapeutic drug and a novel ophthalmic preparation are of great significance for the treatment of dry‐AMD. The purposes of this study were to construct a novel traditional Chinese medicine (Chuanqi Fang) anti‐AMD microemulsion in situ gel for treating dry‐AMD and investigate its characteristic, efficiency, irritation, and tissue distribution. In this study, the characteristic of the Chuanqi microemulsion in situ gel was measured by dynamic light scattering. The electroretinogram (ERG) indicators and the number of retinal pigment epithelial cells were measured to evaluate the therapeutic effect of the novel ophthalmic nanopreparations. Irritation was evaluated according to Technical Guideline Principles (ZGPT4‐1). The analysis of tissue distribution was carried out with LC‐MS. The research showed that the particle size of microemulsion was 38.56 ± 0.21 nm. The Chuanqi microemulsion in situ gel had certain roles in repairing retina damage of the dry‐AMD animal model and showed no irritation. The tissue distribution study found that the microemulsion in situ gel could effectively deliver the drug to the posterior eye of the AMD model rat through the route of cornea‐vitreous body‐retina. In conclusion, this study provided a meaningful research strategy and research basis for the development of new dry‐AMD therapeutic drugs.

PENERAPAN DESAIN EKSPERIMEN DALAM OPTIMASI FORMULA MIKROEMULSI TEA TREE OIL

Microemulsion is a transparent, isotropic and thermodynamically stable preparation. Tea tree oil (TTO) is an essential oil extracted from the leaves of Melaleuca alternifolia by steam distillation which has been proven to have antibacterial and fungal uses. Optimization of microemulsion preparations to obtain preparations with small and stable droplet size is also a challenge. The design of an experiment is to design an experiment with a certain pattern, with a combination of certain input variables that allow to shorten the number of experiments. Based on the research results, it is known that the most influential factor on the microemulsion particle size is the combination of surfactants polysorbate 80 with co-surfactants propyleneglycol.

PREPARATION AND CHARACTERIZATION OF GRAPEFRUIT OIL BASE MICROEMULSIONS OF CAFFEINE

Objective: The objective of the present work was to prepare and characterize grapefruit oil base microemulsions loaded with caffeine as a model hydrophilic compound.
 Methods: The formulation ingredients were selected based on surfactant efficiency and solubility studies. Ternary phase diagrams of grapefruit oil were constructed using the water titration method. Nine O/W microemulsions were constructed and prepared by mixing surfactant system, grapefruit oil, water and caffeine together. The resulting microemulsions were investigated for viscosity using Brookfield viscometer, for pH value using a digital pH meter, and for average particle size and polydispersity index (PDI) using a Zetasizer Nano. Ex vivo skin permeation through porcine ear skin was conducted using a side-by-side diffusion cell. The amount of caffeine was analyzed using HPLC-UV method.
 Results: Tween 20 yielded the highest emulsification ability for grapefruit oil and the highest caffeine solubility. It was selected as a major surfactant. Caffeine was slightly soluble in ethanol and isopropyl alcohol, but sparingly soluble in propylene glycol (PG). These ingredients were used as the cosurfactants. Nine grapefruit oil base microemulsions were prepared and characterized. The pH of microemulsions was within the range of 4.48-5.96. Particle size was in the range of 10.81±0.03 to 62.18±21.04 µm with the PDI of 0.13±0.02 to 0.64±0.11. Viscosity and particle size of microemulsions increased significantly with increasing grapefruit oil or tween 20 content. Addition of PG as cosurfactant resulted in the increases of viscosity, particle size and PDI. Depending on the formulation parameters, the permeation fluxes of caffeine from grapefruit oil base microemulsions were in the range of 28.4±3.4-361.4±15.2 µg/cm2/h.
 Conclusion: The grapefruit oil base microemulsions were successfully formulated. The physical properties and caffeine permeation of these microemulsions were found to be dependent on the grapefruit oil content, tween 20 content, cosurfactant type and content, as well as caffeine loading. The optimal formulation of grapefruit oil base microemulsion suggested composition of 5% grapefruit oil, 50% surfactant system (tween 20 and ethanol at the ratio of 9:1), and water.

Microemulsion and Microporation Effects on the Genistein Permeation Across Dermatomed Human Skin.

This study reports the microemulsion (ME) effects on the permeation of genistein across normal (intact) and microporated human skin. The genistein formulation was optimized to know the stable ME region in the pseudo-ternary phase diagrams and to maximize the skin permeation and retention of genistein. The phase diagrams were constructed with different oil phases, surfactants, and their combinations. The influence of formulation factors on the permeation through intact and microporated human skin was determined. Based on its wide ME region, as well as permeation enhancement effects, oleic acid was used as an oil phase with various surfactants and co-surfactants to further maximize the ME region and skin permeation. The water content in the formulation played an important role in the ME stability, droplet size, and flux of genistein. For example, the ME with 20% water exhibited 4- and 9-fold higher flux as compared to the ME base (no water) and aqueous suspension, respectively. Likewise, this formulation had demonstrated 2- and 4-fold higher skin retention as compared to the ME base (no water) and aqueous suspension, respectively. The skin microporation did not significantly increase the skin permeation of genistein from ME formulations. The ME composition, water content, and to a lesser extent the ME particle size played a role in improving the skin permeation and retention of genistein.

Microemulsion Transdermal Formulation for Simultaneous Delivery of Valsartan and Nifedipine: Formulation by Design.

The objective of the study was to optimize the proportion of different components for formulating oil in water microemulsion formulation meant for simultaneous transdermal delivery of two poorly soluble antihypertensive drugs. Surface response methodology of Box-Behnken design was utilized to evaluate the effect of two oils (Captex 500 - x1 and Capmul MCM - x2) and surfactant (Acrysol EL135 - x3) on response y1 (particle size), y2 (solubility of valsartan), and y3 (solubility of nifedipine). The important factors which significantly affected the responses were identified and validated using ANOVA. The model was diagnosed using normal plot of residuals and Box-Cox plot. The design revealed an inverse correlation between particle size and concentration of Capmul MCM and Acrysol EL 135. However, an increase in concentration of Captex 500 led to an increase in particle size of microemulsion. Solubility of valsartan decreased while that of nifedipine increased with increase in concentration of Captex 500. Capmul MCM played a significant role in increasing the solubility of valsartan. The effect of Acrysol EL 135 on solubility of both drugs, although significant, was only marginal as compared to that of Captex 500 and Capmul MCM. The optimized microemulsion was able to provide an enhancement ratio of 27.21 and 63.57-fold for valsartan and nifedipine, respectively, with respect to drug dispersion in aqueous surfactant system when evaluated for permeation studies. The current studies candidly suggest the scope of microemulsion systems for solubilizing as well as promoting the transport of both drugs across rat skin at an enhanced permeation rate.

Development of cyclosporine A microemulsion for parenteral delivery

The goal of this study was to develop a parenteral microemulsion formulation of cyclosporine A (CyA). The CyA solubility in caprylic capric triglyceride (GTCC), ethyl oleate and soybean oil were determined. The pseudo-ternary diagrams of oil (GTCC), surfactant (Solutol® HS-15), cosurfactants (ethanol/polyethylene glycol 400 [PEG 400] mixture) and water were constructed to identify boundaries for microemulsion existence. The CyA was added at 3, 6 and 9% w/w to the optimal microemulsion composition. Microemulsion particle size, solution viscosity and conductivity were examined. The microemulsion stability and haemolytic potential were examined after dilution in 5% dextrose solution for injection to 1 mg/mL CyA. Microemulsion stability was examined after a three-month storage at 4 and 25 °C. The GTCC was selected as an oil phase for CyA microemulsion based on solubility results. The optimum CyA microemulsion formulation consisted of 2.5% CyA, 9% GTCC, 24% Solutol® HS 15, 8% PEG 400, 4% ethanol and 52.5% water based on weight percent. The average particle sizes of the optimized blank and drug-loaded microemulsions were 68.7 nm and 71.6 nm, respectively and remained unchanged upon 25-fold dextrose dilution. The results of microemulsion physical and CyA chemical were confirmed by a three-month stability study at 4 and 25 °C. In vitro haemolysis studies indicated that CyA microemulsions were well tolerated by erythrocytes. The novel microemulsion formulation of CyA was developed that is suitable for parenteral administration. This new formulation could potentially have less vehicle-associated side effects that current commercial formulation of CyA based on Cremophor® EL and ethanol solution.

Influence of microemulsion-mucin interaction on the fate of microemulsions diffusing through pig gastric mucin solutions.

Mucus layer, a selective diffusion barrier, has an important effect on the fate of drug delivery systems in the gastrointestinal tract. To study the fate of microemulsions in the mucus layer, four microemulsion formulations with different particle sizes and lipid compositions were prepared. The microemulsion-mucin interaction was demonstrated by the fluorescence resonance energy transfer (FRET) method. Moreover, the microemulsions were observed aggregated into micron-sized emulsions by laser confocal microscopy. We concluded the microemulsion-mucin interaction not only led to microemulsions closely adhered to mucins but also destroyed the structure of microemulsions. At last, the diffusion of blank microemulsions and microemulsion-carried drugs (resveratrol and hymecromone) through mucin solutions was determined by the fluorescence recovery after photobleaching (FRAP) method and the Franz diffusion cell method. The results demonstrated the diffusion of microemulsions was significantly hindered by mucin solutions. The particle size of microemulsions had a negligible effect on the diffusion coefficients. However, the type of lipid played an important role, which could form hydrophobic interactions with mucins. Interestingly, microemulsion-carried drugs with different core/shell locations seemed to suffer different fates in the mucin solutions. The drug incorporated in the oil core of microemulsions, resveratrol, was transported through the mucus layer by the carriers, while the drug incorporated in the surfactant shell of microemulsions, hymecromone, was separated from the carriers and diffused toward the epithelium in the form of free molecules.

Evaluating the Effectiveness of β-Carotene Extraction from Pulsed Electric Field-Treated Carrot Pomace Using Oil-in-Water Microemulsion

Thermodynamically stable microemulsions were used to extract β-carotene from pulsed electric field (PEF)-treated carrot pomace. In this study, a three-level Box–Behnken design was used to predict the effect of extraction time (10–110 min), extraction temperature (30–70 °C) and carrot/microemulsion ratio (1:30–1:90 w/w) on the β-carotene content, polydispersity index (PDI) and particle size of the microemulsions. The β-carotene extracted from PEF-treated carrot pomace using microemulsions was higher than untreated carrot pomace. The extraction efficiency of β-carotene using microemulsions was higher compared to 100 % hexane or 100 % glycerol monocaprylocaprate oil. A mathematical model was developed to predict the optimal extraction conditions using transparent microemulsions with high loading of β-carotene, low PDI and small microemulsion particle size. The model predicted that an extraction time of 49.4 min, temperature of 52.2 °C and carrot/microemulsion ratio of 1:70 (w/w) would result in microemulsions with β-carotene loading of 19.6 μg/g, PDI of 0.27 and particle size of 74 nm. This study demonstrates the potential of using oil-in-water microemulsions as extraction media for β-carotene.

Formulation development and in vitro evaluation of solidified self-microemulsion in the form of tablet containing atorvastatin calcium

Aim: The objective of our present study was to prepare solid self-microemulsion in the form of tablet of a poorly water soluble drug, Atorvastatin calcium (ATNC) to increase the solubility, dissolution rate, and minimize the hazards experienced from liquid emulsions.Materials and methods: Self-microemulsifying ATNC tablet was formulated mainly by using self-emulsifying base, solidifying agent silicon dioxide and sodium starch glycolate as tablet disintegrant. Self-emulsifying base containing Transcutol P, Gelucire 44/14, and Lutrol F68 with their ratios in the formulation, were best selected by solubility study and ternary phase diagram in different vehicles. Particle size of microemulsion from tablet, physical parameters of the tablet and drug content has been checked. In vitro drug release rate has been carried out in phosphate buffer medium (pH 6.8). Physicochemical characterization of the drug in the optimized formulation has been performed to check drug-excipient incompatibility, if any.Results: Average particle diameter of the emulsions formed from the tablet was found to be below 100 nm in case of formulation F4 and F5, which indicated microemulsions has been formed. In vitro drug release from the formulations F3, F4, and F5 was found to be >90%, indicated the enhancement of solubility of ATNC compared to parent drug. Differential thermal analysis (DTA), Powder X-ray Diffraction (X-RD) and Fourier transform infra red (FTIR) study proved the identity of the drug in the optimized formulation.Conclusion: The tablet form of self-microemulsifying (SME) drug delivery is good for solubility enhancement.

A new self-microemulsifying mouth dissolving film to improve the oral bioavailability of poorly water soluble drugs

A new self-microemulsifying mouth dissolving film (SMMDF) for poorly water-soluble drugs such as indomethacin was developed by incorporating self-microemulsifying components with solid carriers mainly containing microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hypromellose. The uniformity of dosage units of the preparation was acceptable according to the criteria of Chinese Pharmacopoeia 2010. The SMMDF was disintegrated within 20 s after immersion into water, released completely at 5 min in the dissolution medium and achieved microemulsion particle size of 28.81 ± 3.26 nm, which was similar to that of liquid self- microemulsifying drug delivery system (SMEDDS). Solid state characterization of the SMMDF was performed by SEM, DSC and X-ray powder diffraction. Results demonstrated that indomethacin in the SMMDF was in the amorphous state, which might be due to self-microemulsifying ingredients. Pharmacokinetic parameters in rats including Tmax, Cmax, AUC were similar between the SMMDF and liquid SMEDDS. AUC and Cmax from the SMMDF were significantly higher than those from the common mouth dissolving film or the conventional tablet, and Tmax from SMMDF group was also significantly decreased. These findings suggest that the SMMDF is a new promising dosage form, showing notable characteristics of convenience, quick onset of action and enhanced oral bioavailability of poorly water-soluble drugs.

Preparation and evaluation of flurbiprofen-loaded microemulsion for parenteral delivery

The purpose of this study was to improve the solubility of flurbiprofen, a poorly water-soluble drug, in an oil-in-water (o/w) microemulsion that is suitable for parenteral administration. Microemulsions with varying ratios of oil to surfactant were prepared with ethyl oleate, Tween 20 and isotonic solution. The effect of formulation variables on the particle size of microemulsion and solubility of flurbiprofen in microemulsion system was investigated. The pharmacokinetic parameters of flurbiprofen after intravenous administration of flurbiprofen-loaded microemulsion were compared with those of a solution of the drug. The mean droplet diameter of microemulsion containing less than 1% (w/w) of flurbiprofen was below 100 nm. The maximum solubility of flurbiprofen in the microemulsion system was found to be 10 mg/ml. However, the mean droplet diameters of flurbiprofen-loaded o/w microemulsions tend to be increased at room temperature. The pharmacokinetic parameters of flurbiprofen after intravenous administration of flurbiprofen-loaded microemulsion to rats were not significantly different from those of flurbiprofen in phosphate-buffered saline solution. It can be concluded that microemulsions of flurbiprofen prepared with ethyl oleate and Tween 20 can be used as a parenteral drug carrier for this and other poorly water-soluble drugs, provided that physical stability can be properly addressed.

Enhanced intestinal absorption of an RGD peptide from water-in-oil microemulsions of different composition and particle size

The fibrinogen receptor antagonist SK&F 106760 is a water-soluble tetrapeptide ( M r 634) with very low oil/water partitioning and membrane permeability. Thus, the intraduodenal bioavailability of this peptide in the rat from a saline formulation was found to be less than 1%. Upon formulation, however, in w/o microemulsions of different composition and particle size, the intraduodenal bioavailability of SK&F 106760 was increased up to 29% depending on the microemulsion composition. There was no apparent correlation between the particle size of microemulsions (mean droplet diameter of 0.010–1.0 μm) and enhanced absorption. None of the investigated microemulsions induced gross changes in gastrointestinal mucosa at a dosing volume of 3.3 ml/kg. Lipids containing medium-chain fatty acids play a major role on the observed absorption enhancement. These findings further support the use of microemulsion formulations for oral drug/peptide delivery, provided however, that development issues with these systems are properly addressed.