Microemulsion Research Articles

N-octadecyl lactose-amide modified microemulsions as targeting delivery carrier for α-linolenic acid: In vitro evaluation and interaction mechanism

Targeting delivery for nutritional factor is increasingly paid in research field of agricultural and food science. In this present work, a novel asialoglycoprotein receptor (ASGPR)-targeted α-linolenic acid (ALA)-loaded microemulsions (MEs) for hepatocellular carcinoma (HCC) was designed. The N-octadecyl lactose-amide (NOL) was synthesized and used as active targeting ligand. The structure of NOL was characterized by Fourier transform infrared spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR). The load-ALA MEs as delivery carrier with or without NOL were evaluated by in vitro release and viability effect to hepa1-6 cells. Notably, NOL-modified MEs loading ALA (NOL-ALA-ME) consisted of spheroidal droplets with a particle size of 10–20 nm. Compared with the no-targeted ligand MEs, NOL-ALA-ME possessed a sustained release characteristic in vitro. Due to specific ligand-receptor interactions, NOL-ALA-ME demonstrated a more remarkable selective toxicity to Hepa1-6 cells. Molecular docking of ligand and receptor compounds indicated a docking score of −5.4 kcal/mol, meaning a strong targeting binding force between ligand and receptor, theoretically supports the results of cell experiments. These findings could offer significant insight into MEs as targeting delivery carrier, which may be regarded as a promising strategy for functional enhancement of active components in agricultural and food industry.

Characterization of w/o-type Microemulsions Containing l-Menthol-based Deep Eutectic Solvents for Use in Transdermal Drug Delivery

Abstract We investigated the structural properties of microemulsions (MEs) dispersed in oil base including hydrophobic deep eutectic solvents (DESs) and their skin permeabilities. The results showed that the addition of DESs can improve the skin penetration of monodispersed MEs by disturbing the lipid structures in the stratum corneum. Further addition of DESs caused the structural transition of MEs from a sphere to a cylinder and a bicontinuous system and decreased reduced skin penetration.

Nanoemulsion supported microemulsion electrokinetic chromatography coupled with selected preconcentration techniques as an approach for analysis of highly hydrophobic compounds

In this paper, an oil-in-water (O/W) nanoemulsion (NE) prepared by water cold dilution of an O/W microemulsion (ME) was introduced as a sample matrix in microemulsion electrokinetic capillary chromatography (MEEKC) for the highly hydrophobic compounds analysis. Several model compounds with log PO/W values in the 4.1–10.9 range, from different chemical groups, including retinol, α-tocopherol, cholecalciferol, phylloquinone, menaquinone-7, dichlorodiphenyltrichloroethane, ivermectin have been tested. As a proof of the concept of NE formation, a dynamic light scattering technique was employed to determine the size distribution profile of NE particles. Moreover, due to relatively low conductivity of the NE matrix (50–100 times lower in comparison to the separation buffer) and a negative electric charge provided to hydrophobic compounds through NE dispersed phase, NE matrices have been combined with preconcentration techniques based on electrokinetic dosing, namely field amplified sample injection (FASI) and pressure assisted electrokinetic injection (PAEKI). The detection limits for vitamin K1 and K2-MK7 in the NE matrix in combination with FASI (NE–MEEKC–FASI) as well as PAEKI (NE–MEEKC–PAEKI) were up to 42.9 and 12.1 ng mL−1, respectively. In comparison to standard hydrodynamic injection for microemulsion sample matrix NE–MEEKC–PAEKI grant 45-fold improvement in signal sensitivity. The study presents an innovative approach, as it enables the use of preconcentration techniques for highly hydrophobic compounds (log PO/W > 4), which was not previously possible for implementation in the electromigration techniques. Likewise, the use of organic solvents has been reduced by using ME as a solvent for stock solutions and diluting with water prior to the analysis. The application to real samples was investigated using a dietary supplement containing vitamin K2-MK7 obtained from the fermentation product of soybeans.

A Systemic Review on Micro-emulsion: Liquid Dosage form for Topical Drug Delivery System

Microemulsions (ME) is a system that combines water, oil, and an emulsifier / surfactant which is a form of volatile liquid, homogeneous and kinetically stable. Microemulsion is an attractive drug delivery system for topical administration. Due to its solubility, mild skin irritation, and watery swelling are used in the Topical Drug Delivery System (TDDS). By improving the quality of skin texture, it provides a level of penetration. The function of skin balance is to limit the penetration of bacteria, viruses, and other environmental factors. With standard drugs, skin penetration may take time and have not been able to provide immediate action. So, in this case, we used the Microemulsion-based Topical Drug Delivery system. Microemulsion increases solubility, protects the drug from environmental factors and improves drug bioavailability. MEs provide high penetration and the ability to penetrate into the skin. Because of this, the immediate action of the drug can occur in the infected area. Due to the presence of a hydrophilic and lipophilic environment, it provides outstanding biocompatibility. There are several test frames used to maintain stability, microemulsion kinetics.

Multiphase Drug Distribution and Exchange in Oil-in-Water Nanoemulsion Revealed by High-Resolution 19F qNMR.

An oil-in-water (o/w) nanoemulsion (NE), composed of oil globules, stabilized by a surfactant, and dispersed in an aqueous phase, is increasingly developed in complex drug formulation. Kinetically stable NEs are used to formulate hydrophobic drugs and typically provide higher dosage strengths and better content uniformity. However, little is known accurately about drug distribution in its multiphase solution, especially for the possible drug presence in the surfactant (s) phase, the interface layer between the dispersed oil (o) and the continuous water (w) phases. Here, high-resolution 19F quantitative NMR spectroscopy was applied directly and noninvasively on an o/w NE drug product containing difluprednate (DFPN). The well-resolved 19F peaks of DFPN depended on the shielding molecules in each phase, which revealed mass-balanced DFPN distribution in multiple phases of (w), (s), and (o) of NE globules at a quantity of 1.8 ± 0.1, 35 ± 2, and 59 ± 3% per labeled content, respectively. Furthermore, the dilution-dependent 19F peak line broadening and shift suggested a millisecond dynamic exchange between the NE and the less-noticed smaller but thermodynamically stable microemulsion (ME) globules in NE solution. The high-resolution NMR result revealed that the drug availability could be quickly achieved using an o/w NE formulation because of the drug multiphase distribution and the ME-assisted fast drug exchange among globules.

Improvement of solubility, stability and antioxidant activity of carotenoids using deep eutectic solvent-based microemulsions

Natural carotenoids have been widely used as colorants and antioxidants in process of food, medicine, and cosmetic. However, the carotenoids have low bioactivity in vivo due to poor water-solubility. To enhance the solubility, stability and antioxidant activity of carotenoids, novel microemulsions (MEs) composed with deep eutectic solvents (DESs), tween 80 and water were developed as alternatives to organic solvents. The phase diagrams and physicochemical properties (viscosity, pH, and diameter) of the DES-based MEs were investigated at different temperatures. Then the solubility distribution, storage stability and DPPH free radical-scavenging activity of three carotenoids (astaxanthin, astaxanthin ester and lutein) in the MEs were evaluated. Compared with ethanol, methanol, and acetone, all the DES-based MEs studied significantly enhanced the solubility of the carotenoids due to the stronger hydrogen bonding and Van der Waals interactions. The highest solubilities of 0.27, 473.63, and 12.50 mg/mL for astaxanthin, astaxanthin ester and lutein, respectively, were observed in the MEs containing DES (DL-menthol:acetic acid = 1:2) at 35 ℃. Moreover, astaxanthin ester can be well preserved in the MEs containing DES (DL-menthol:octanoic acid = 1:2) with a half-life of more than 69 days. In addition, the DPPH scavenging capacities of the three carotenoids in all the MEs were higher than the organic solvents. The results revealed that the DES-based MEs with low viscosity (<0.2 Pa•s) and mild acidic pH (4−5) are potential solvents for natural carotenoids in food processing and storage, medicine making, as well as biomaterials processing.

Microemulsification of nonvolatile components of Melaleuca alternifolia and borneol can effectively defend Rhizoctonia solani

The exploration of plant bioactive components for plant protection is significant for sustainable development of agriculture. Although the essential oil of Melaleuca alternifolia Maiden & Betche Cheel has been widely applied in many fields, its non-volatile active components are not fully utilized in agriculture. This study found that nonvolatile components of M. alternifolia possessed fungicidal activity against Rhizoctonia solani Kühn. The n-butanol extract of M. alternifolia mixed with borneol at a ratio of 5:1 enables good synergism in terms of antifungal activity. Importantly, the fungicidal activity against R. solani can be further significantly improved by microemulsification. The 10% microemulsion (ME) possessed significant preventive and curative efficacy against R. solani in rice plants with control efficacy of 85.29% and 76.87% at 300 mg/L, respectively. They are comparable to the control efficacy of 8% validamycin A aqueous at 300 mg/L. The 10% ME could also suppress the formation of sclerotia of R. solani even at a low concentration of 50 mg/L. Primary study on the mechanism of action indicated that 10% ME destroyed the cell membrane and mitochondria, triggered the release of cellular contents, produced reactive oxygen species (ROS) and reduced the number of cell nuclei in R. solani mycelia. This study demonstrates that the nonvolatile components of plants are valuable resources for the development of plant-source green formulations for the control of phytopathogenic bacteria and fungi.

Ex vivo permeation parameters and skin deposition of melatonin-loaded microemulsion for treatment of alopecia

BackgroundMelatonin (MEL) is a powerful antioxidant molecule with anti-androgenic property. A microemulsion (ME) system loaded with MEL was designed for treatment of androgenic alopecia. Pseudo-ternary phase diagram was constructed, and ME formulae were developed using coconut oil, Tween 80 and PEG 400. In the present study, MEL ME was characterized and evaluated for droplet size, polydispersity index, zeta potential, morphology using TEM imaging. MEL ex vivo permeation study through rat skin followed by tape stripping for stratum corneum (SC) was performed for different ME formulae, to determine skin permeation parameters and detect SC-MEL deposition.ResultsSpherical and uniform particles of MEL-loaded microemulsion were formulated with high stability. In ex vivo permeation study, MEL ME exhibited low steady-state skin flux along with pronounced SC deposition which prevailed a controlled release manner.ConclusionThe results suggested that MEL ME could be a promising candidate for further permeation and in vivo studies for androgenic alopecia treatment.

Interactions of basic compounds with ionic liquids used as oils in microemulsion liquid chromatography

Aqueous microemulsions (MEs), where an oil coexists with water in the presence of the anionic surfactant sodium dodecyl sulphate (SDS), have been proposed as a solution to decrease the amount of organic solvent in the mobile phase needed in reversed-phase liquid chromatography (RPLC). However, the oil phase of a typical ME is volatile, toxic and flammable, and although it is added in a small amount, it would be desirable to avoid it from an environmental perspective. This is the reason for the proposal of Peng et al. (J. Chromatogr. A 1499 (2017) 132‒139) to replace the oil in microemulsion liquid chromatography (MELC) by the apolar ionic liquid (IL) 1-hexyl-3-methylimidazolium hexafluorophosphate ([C6C1IM][PF6]), to analyse neutral phenolic acids at acidic pH. Based on this report, an MELC procedure is here proposed for β-adrenoceptor antagonists, which are basic compounds where the dominant species is cationic. To verify the formation of MEs containing SDS and IL, and elucidate the interactions between the cationic basic compounds with the SDS anion, and the cation and anion in the IL, an extensive study was carried out with several methylimidazolium ILs containing the cations [C2C1IM]+, [C4C1IM]+, or [C6C1IM]+, combined with the anions Cl–, BF4–, or PF6–, using 1-butanol as co-surfactant. The behaviour was compared with that observed in classical MELC with octane, micellar liquid chromatography with SDS and 1-propanol, and RPLC with mobile phases containing an IL and acetonitrile.

Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics.

The purpose of our study was to improve the solubility, bioavailability, and efficacy of zotepine (ZTP) by brain-targeted intranasal delivery of microemulsion (ME) and its physicochemical properties, the pharmacokinetic and pharmacodynamic parameters were evaluated. The optimized ME formulations contain 10% w/w of oil (Capmul MCM C8, monoglycerides, and diglycerides of caprylic acid), 50% w/w of Smix (Labrasol and Transcutol HP, and 40% w/w of water resulting in a globule size of 124.6 ± 3.52 nm with low polydispersity index (PDI) (0.212 ± 0.013) and 2.8-fold higher permeation coefficient through porcine nasal mucosa compared to pure drug). In vitro cell line studies on RPMI 2650, Beas-2B, and Neuro-2A revealed ZTP-ME as safe. ZTP-ME administered intranasally showed higher AUC0–t24 (18.63 ± 1.33 h × µg/g) in the brain by approximately 4.3-fold than oral ME (4.30 ± 0.92 h × µg/g) and 7.7-fold than intravenous drug solutions (2.40 ± 0.36 h × µg/g). In vivo anti-schizophrenic activity was conducted using catalepsy test scores, the formulation showed better efficacy via the intranasal route; furthermore, there was no inflammation or hemorrhage in the nasal cavity. The results concluded that the ZTP microemulsion as a safe and effective strategy could greatly enhance brain distribution by intranasal administration.

Microemulsions based on peony (Paeonia suffruticosa Andr.) seed oil and its fatty acids: Product development and stability enhancement

Peony (Paeonia suffruticosa Andr.) originated in China and has long been popular worldwide as an ornamental crop. In recent years, peony seed oil (PSO) as edible oil has received extensive attention due to its richness in unsaturated fatty acids, especially α-linolenic acid (ALA). In this work, fatty acid mixture-1 (FAM-1) and fatty acid mixture-2 (FAM-2) with different ALA concentrations were prepared from PSO by saponification and freezing crystallization. Pseudo-ternary phase diagrams were constructed to determine the composition and proportions of microemulsions (MEs), which were used to embed PSO and FAM. Based on pseudo-ternary phase diagrams, PSO ME prepared possessed a droplet size of 54.6 nm using a mixture of Tween 80 and Span 80 as the surfactant, while FAM-1 ME and FAM-2 ME owned droplet sizes of 30.1 and 29.7 nm using Tween 20 as the surfactant, respectively. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) analysis confirmed that the MEs had good dispersibility, and rheological analysis demonstrated excellent resistance to shearing rate changes. Besides, three MEs all exhibited good stability at 4 °C by microemulsification during the 60-day storage period in terms of droplet size, pH, and electrical conductivity. The water solubility and viscosity exhibited by the three synthetic MEs showed large potential to expand the application in cosmetics, medicine, and food industry.

Investigation of transdermal permeation of atorvastatinloaded microemulsions

Purpose: To develop microemulsions containing atorvastatin for transdermal application, which will improve the bioavailability and reduce the side effects associated with the oral administration of atorvastatin.Methods: Atorvastatin-loaded microemulsions (MEs) were developed using tween 80 as a nonionic surfactant, isopropyl myristate, polyethylene glycol 400 and dimethyl sulfoxide. Their droplets’ size, and rheological properties were estimated, with the diffusion through the rat’s skin being evaluated using Franz diffusion cells. Furthermore, the in vivo transdermal and oral bioavailability, as well as the toxicity of formulation, were assessed in rats.Results: The results showed that the MEs have a droplet size lower than 100 nm and low Newtonian viscosity. In addition, a flux rate of atorvastatin as high as 10.078 μg/cm2.h was achieved after the loading of the MEs. The in vivo transdermal application maintained a steady state concentration of 1.02μg/mL for 48 h, in comparison to a maximum concentration of 7.7 μg/mL after 2.74 h following oral administration at the same dosing level. Moreover, the transdermally treated rats did not elicit skin irritation.Conclusion: The developed atorvastatin MEs for transdermal application delivers the drug to achieve a controlled plasma level, as well as reduce dosing frequency and toxicity in rats when compared to oral administration. Therefore, the formulation has a potential for development for use in humans.

Incorporation of essential oil from Vitex gardneriana (Lamiaceae) in microemulsions systems based on mineral and cottonseed oils increased its bioactivity against a coconut pest mite

Coconut (Cocos nucifera L.) is an important cash crop for Asia, Africa and tropical America. The coconut mite, Aceria guerreronis Keifer (Acari: Eriophyidae) is a major coconut pest, inflicting heavy damage to fruits, thereby reducing yields and farmers profitability. Previous research has demonstrated that high contents of sesquiterpenes compounds present in the essential oil of Vitex gardneriana Schauer (Lamiaceae) (EOVG) showed high potential to control A. guerreronis. Systems stabilized by surfactants, such as microemulsions (MEs), are promising to carry essential oils due to their solubilization and protection properties, generally allow for greater spreadability, wettability and have thermodynamic stability and lower viscosity. Here, we compared the acaricidal activity of MEs containing EOVG a based cottonseed oil (CO) and mineral oil (MO) as different oily phases. MEs formulations were obtained through the pseudoternary phase diagram using a 1:1 mixture of polysorbate 80: propylene glycol as surfactant and co-surfactant, respectively, and CO and MO as oily phases and water as aqueous phase. The MEs were characterized by polarized light microscopy, dynamic light scattering as well as by rheological behavior. Results based on concentration-mortality bioassays, showed that the toxicity of ME-CO containing EOVG was higher (LC50 = 195 ppm) in comparison with ME-CO without EOVG (LC50 = 669 ppm). Similarly, adding EOVG to ME-MO increased the toxicity further (LC50 = 120 ppm). Moreover, the LC50 of ME with and without EOVG for A. guerreronis was higher than the LC50 determined for the EOVG alone (LC50 = 888 ppm). The MEs containing EOVG in their LC80 and mainly LC50, repelled the mite. Overall, our results indicate that the MEs hold potential for controlling A. guerreronis, especially when EOVG was added with both oil phases.

Phospholipid-Based Microemulsions for Cutaneous Imiquimod Delivery.

Imiquimod (IMQ) is a potent immune response modifier with antiviral and antitumor properties. IMQ’s low aqueous solubility and unsatisfactory cutaneous permeability limit its formulation into effective dosage forms. This work aimed to develop IMQ-loaded microemulsions (MEs) based on phospholipids and oleic acid to improve IMQ penetration into the epidermis. A pseudo-ternary phase diagram was constructed, and the microstructure of the formulations was examined by measuring the conductivity values. Selected MEs were characterized and studied for their ability to deliver IMQ into and through ex vivo human skin. ME1 with 1% IMQ (bicontinuous ME with Bingham rheology) delivered similar IMQ quantities to the human epidermis ex vivo as the commercial product while having a 5-fold lower IMQ dose. IMQ was not detected in the acceptor phase after the permeation experiment, suggesting a lower systemic absorption risk than the established product. Infrared spectroscopy of the stratum corneum revealed less ordered and less tightly packed lipids after ME1 application. The ME1-induced barrier disruption recovered within less than 5 h after the formulation removal, as detected by transepidermal water loss measurements. In conclusion, our findings demonstrate that phospholipid and oleic acid-based MEs could become a promising alternative for topical IMQ administration.

In Vitro Evaluation of a Foamable Microemulsion Towards an Improved Topical Delivery of Diclofenac Sodium.

Topical microemulsion (ME) might provide a novel and advanced transdermal delivery system due to the enhances of drug solubility and permeability across the stratum corneum. Foams are topical delivery systems that have excellent patient compliance, acceptability, and preference. Therefore, this study aimed to investigate a foamable microemulsion as an alternative topical and transdermal dosage form for diclofenac sodium (DS). The physicochemical properties (optical clarity, percentage transmittance, homogeneity, consistency of formulation, particle size, zeta potential, conductivity, viscosity, and morphology, etc.) of the DS-loaded ME were investigated. The foam stability of both drug-free ME and DS-loaded ME was measured. The foam quality was evaluated, and the chemical stability over 90days was determined. Franz diffusion cells were employed to assess the in vitro drug release of a foamed DS-loaded ME and compared with a commercial topical product. A foamable and stable DS-loaded ME that maintained small particle sizes and constant zeta potential and was transparent and translucent in appearance after 90days was successfully produced. The foam of the DS-loaded ME was physically more stable compared to the drug-free foam. The foam had an increased drug release rate compared to the commercial product. The foamable DS-loaded ME has a great potential to enhance the transdermal delivery of DS after topical administration. Foamed DS-loaded ME is a promising alternative to the current topical formulation of DS.

Formulation of biocompatible microemulsions for encapsulation of anti-TB drug rifampicin: A physicochemical and spectroscopic study

Surfactant-based microemulsions have emerged as an advanced material for universal drug carriers for poorly soluble drugs. These microemulsions (MEs) are based on ionic liquid as oil in presence of traditional surfactants which have been receiving ample attention from research communities all over the world. In this study, we have reported oil-in-water MEs containing a hydrophobic ionic liquid (IL), 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) as oil phase, nonionic surfactants Brij35/Triton X100 and water. The microstructure of these BmimPF6-in-water (IL/w) MEs were identified by using UV-Vis and fluorescence spectroscopy. The breaks observed in the absorption spectra of both probe (p-nitroanaline) and drug (rifampicin) versus wt% of IL can be used to confirm the formation of MEs. Similar behavior has been observed in the emission spectra of fluorescence probe (pyrene) and drug in presence of varied wt% of IL which supported the results of the absorption spectroscopy. The results from dynamic light scattering (DLS) and scanning electron microscopy (SEM) measurements showed that the MEs had a nearly monodisperse droplet size distribution (PDI < 0.4) which indicates the homogeneity in distribution of the ME formulations. The incorporation of rifampicin-drug in the MEs shows notable changes which suggests the accumulation of drug in the palisade layers of the MEs. Further, the surface free energy properties of the MEs are explored from surface tension (γ) measurements. The changes in γ in these different MEs may be due to the changes in microstructures of the ME systems which can be helpful to recognize the transitions occurring in the ME structures. This study offers a better understanding of MEs features and paves path towards the potential applications of MEs in pharmaceutical industry.

Comparative Analysis of the Antimicrobial Activity of Essential Oils and Their Formulated Microemulsions against Foodborne Pathogens and Spoilage Bacteria.

The antimicrobial activity of several essential oils (EOs) and their related microemulsions (MEs) was investigated. EOs were obtained from Cannabis sativa L. cv CS (C. sativa), Carum carvi L. (C. carvi), Crithmum maritimum L. (C. maritimum), Cuminum cyminum L. (C. cyminum), x Cupressocyparis leylandii A.B. Jacks & Dallim. (C. leylandii), Cupressus arizonica Greene (C. arizonica), Ferula assa-foetida L. (F. assa-foetida)., Ferula gummosa Boiss. (F. gummosa), Juniperus communis L. (J. communis), Juniperus x pfitzeriana (Spath) P.A. Schmidt (J. pfitzeriana), Pimpinella anisum L (P. anisum). Preliminary screening revealed that Cuminum cyminum, Crithmum maritimum, and Pimpinella anisum (10% v/v) were effective against all tested microorganisms (Escherichia coli ATCC 35218, Listeria monocytogenes ATCC 7644, Staphylococcus aureus ATCC 29213, Pseudomonas fluorescens DSM 4358, and Candida albicans ATCC 10231), with growth inhibition diameter from 10 to 25 mm. These EOs were used to formulate the MEs with an average size < 50 nm and a good stability over 30 days. EOs’ antimicrobial activity was further enhanced in the MEs, with a generalized lowering of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. C. cyminum-ME reached, in most cases, MIC two times lower (0.312%) than the corresponding EO (0.625%) and even eight times lower against S. aureus (0.156 vs. 1.25%). A more remarkable microbicide effect was noted for C. cyminum-ME, with MBC values eight times lower (from 0.312 to 0.625%) than the corresponding EO (from 2.5 to 5%). Overall, MEs resulted in an efficient system for EOs encapsulation, enhancing solubility and lowering concentration to exert antimicrobial efficacy.

Microemulsions formed by PPG-5-CETETH-20 at low concentrations for transdermal delivery of nifedipine: Structural and in vitro study

Nifedipine is a potent anti-hypertensive, which is poorly orally bioavailable on account of first-pass metabolism, short half-life, and low water solubility. This study aimed to develop a microemulsified system with low surfactant concentration and to evaluate the influence of microemulsion (ME) phase behavior on skin permeation of nifedipine, as drug model. Thereafter, MEs were obtained using PPG-5-CETETH-20, oleic acid, and phosphate buffer at pH 5.0. The selected MEs were isotropic, with droplet diameters less than 10 nm, polydispersity index < 0.25, and pH between 5.0 and 5.2. MEs presented low viscosity and Newtonian behavior. SAXS results confirmed bicontinuous and oil-in-water (o/w) MEs formation. The presence of the drug promoted only very slight modifications in the ME structure. The MEs presented ability to deliver nifedipine via the transdermal route when in comparison with the control. Nevertheless, the skin permeated and retained amounts from the o/w and bicontinuous formulations did not differ significantly. The ATR-FTIR demonstrated that both formulations promoted fluidization and disorganization of lipids and increased the drug diffusion and partition coefficients in the skin. In conclusion, PPG-5-CETETH-20 MEs obtained proved to be effective skin permeation enhancers, acting by rising the coefficients of partition and diffusion of the nifedipine in the skin.

Formulation and Optimization of Progesterone Microemulsion Using Simplex Lattice Mixture Design

Progesterone (P4) is a neurosteroid hormone synthesized in both males and females, it is widely used in reproductive health and hormone replacement therapy. The aim of this study was to develop microemulsions (ME) and optimization of P4 microemulsion using a simplex lattice mixture design for enhancing the transdermal delivery of P4. Pseudo-ternary phase diagrams were generated to find the optimal ratio of the microemulsion constituents. The solubilities of P4 in different oils, surfactants, and co-surfactants were determined. The ME formulations of P4 were then prepared and optimized by simplex lattice mixture design. Each ME formulation was characterized for size, PDI, zeta potential, drug content, in vitro permeation study, and drug permeation in porcine skin. The result showed that the optimal ME formulation composed of 34.97 %w/w eugenol as the oil phase, 18.35 %w/w Labrasol® as the surfactant, 36.69 %w/w ethanol as the cosurfactant, and 10.00% w/w water containing HPβCD (1.0 M). The optimized ME showed an appropriate size of about 178 ± 42 nm with a low polydispersity index (PDI) and almost neutral charge. The drug content of the optimized ME was about 19.9 ± 0.6 %w/w. The results of in vitro permeability showed that the optimized ME formulation was significantly higher than the drug suspension. Moreover, the P4 from the optimized ME was able to be deposited in the dermis (1.07 mg) at a higher extent than in the stratum corneum (0.65 mg). In conclusion, this study explored a formulation approach to improve the transdermal permeation of P4.

Microemulsions as nanocarriers for oral and transdermal administration of enoxaparin

Low and high molecular weight heparins are essential anticoagulant drugs and usually given subcutaneously. In this research, the oral and transdermal absorption of enoxaparin via nonionic microemulsions as liquid nanocarriers was evaluated. The enoxaparin was incorporated into different nonionic inverted microemulsions (MEs). The microemulsions were characterized for their droplets' size, rheological properties and drug encapsulation. In addition, the flux of the loaded enoxaparin MEs was assessed using Franz diffusion cells. Furthermore, the efficacy of these enoxaparin-loaded MEs was evaluated in rats after oral administration and transdermal application in comparison to the subcutaneous solution. The results showed that these formulations have a droplets’ size in the range of 200 nm or less, and had Newtonian viscosity. The fitting of penetration data using Franz diffusion cells revealed a flux of enoxaparin through the epidermis as high as 3.47 ± 0.85 mg/cm2 h. Moreover, the recorded response after the oral administration and transdermal application showed a clear increase in the clotting time; and this response changed with time. Furthermore, the transdermal application showed a higher bioavailability in comparison to the oral administration. This novel in vitro and in vivo research disclosed the possibility of using nonionic microemulsions to facilitate the oral and noninvasive transdermal applications of enoxaparin.