Microemulsion-based Gels Research Articles

Investigation of microemulsion system for transdermal delivery of itraconazole.

A new oil-in-water microemulsion-based (ME) gel containing 1% itraconazole (ITZ) was developed for topical delivery. The solubility of ITZ in oils and surfactants was evaluated to identify potential excipients. The microemulsion existence ranges were defined through the construction of the pseudoternary phase diagrams. The optimized microemulsion was characterized for its morphology and particle size distribution. The optimized microemulsion was incorporated into polymeric gels of Lutrol F127, Xanthan gum, and Carbopol 934 for convenient application and evaluated for pH, drug content, viscosity, and spreadability. In vitro drug permeation of ME gels was determined across excised rat skins. Furthermore, in vitro antimycotic inhibitory activity of the gels was conducted using agar-cup method and Candida albicans as a test organism. The droplet size of the optimized microemulsion was found to be <100 nm. The optimized Lutrol F 127 ME gel showed pH in the range of 5.68±0.02 and spreadability of 5.75±1.396 gcm/s. The viscosity of ME gel was found to be 1805.535±542.4 mPa s. The permeation rate (flux) of ITZ from prepared ME gel was found to be 4.234 μg/cm/h. The release profile exhibited diffusion controlled mechanism of drug release from ME ITZ gel. The developed ME gels were nonirritant and there was no erythema or edema. The antifungal activity of ITZ showed the widest zone of inhibition with Lutrol F127 ME gel. These results indicate that the studied ME gel may be a promising vehicle for topical delivery of ITZ.

Nanocarrier-based hydrogel of betamethasone dipropionate and salicylic acid for treatment of psoriasis

Introduction:Betamethasone dipropionate (BD) has anti-inflammatory, immunomodulatory, and antiproliferative activity. The aim of the current work was to test the hypothesis that the addition of corticosteroid such as BD and a keratolytic agent such as salicylic acid in nanocarrier based microemulsions formulation would result in enhancement and sustaining of corticosteroid delivery rate leading to better anti-psoriatic activity. Clinical use of BD is restricted to some extent due to its poor permeability across the skin. So to increase its permeation across the skin, microemulsion-based gel formulations were prepared and characterised.Materials and Methods:Microemulsions were prepared by aqueous phase titration method, using oleic acid:sefsol (1.5:1), Tween 20, isopropyl alcohol, and distilled water as the oil phase, surfactant, cosurfactant and aqueous phase, respectively. Selected formulations were subjected to physical stability studies and consequently in vitro skin permeation studies. Surface studies of optimized formulation were done by transmission electron microscopy. In vivo anti-inflammatory activity was done by carageenan-induced raw paw edema method.Results:The droplet size of microemulsions ranged from 60 to 190 nm. The optimized formulation exhibited viscosity 28.55 ± 2.03 mP, refractive index 1.409, pH 6.4, and conductivity 10-4 scm-1. The optimized microemulsion was converted into hydrogel using carbopol 934, and salicylic acid was incorporated into it. Drug deposition in skin was found to be 29.73 μg/mg. Assessment of skin permeation was done by histopathology studies which indicated changes in the structure of epidermal membrane of skin. In vivo anti-inflammatory activity indicated 72.11% and 43.96% inhibition of inflammation in case of developed microemulsion gel and marketed gel, respectively.Conclusions:The developed microemulsion gel containing BD and salicylic acid provided sustained and good anti-inflammatory activity for the treatment of psoriasis.

Microemulsion-based Hydrogel Formulation of Itraconazole for Topical Delivery

The present study was aimed at preparing microemulsion-based hydrogel (MBH) for the skin delivery of itraconazole. Microemulsion prepared with Transcutol as a surfactant, benzyl alcohol as an oil and the mixture of ethanol and phasphatidyl choline (3:2) as a cosurfactant were characterized by solubility, phase diagram, particle size. MBHs were prepared using 0.7 % of xanthan gum (F1-1) or carbopol 940 (F1-2) as gelling agents and characterized by viscosity studies. The in vitro permeation data obtained by using the Franz diffusion cells and hairless mouse skin showed that the optimized microemulsion (F1) consisting of itraconazole (1% w/w), benzyl alcohol (10% w/w), Transcutol (10% w/w) and the mixture of ethanol and phospahtidylcholine (3:2) (10% w/w) and water (49% w/w) showed significant difference in the flux (~1 µg/ cm 2 /h) with their corresponding MBHs (0.25-0.64 µg/cm 2 /h). However, the in vitro skin drug content showed no significant difference between F1 and F1-1, while F1-2 showed significantly low skin drug content. The effect of the amount of drug loading (0.02, 1 and 1.5% w/w) on the optimized MBH (F1-2) showed that the permeation and skin drug content increased with higher drug loading (1.5%). The in vivo study of the optimized MBH (F1-2 with1.5% w/w drug loading) showed that this formulation could be used as a potential topical formulation for itraconazole. Key wordsItraconazole, Benzyl alcohol, Microemulsion-based gel, Topical skin delivery

Microemulsion-Based Vaginal Gel of Clotrimazole: Formulation, In Vitro Evaluation, and Stability Studies

The objective of the present investigation was to develop and evaluate microemulsion-based gel for the vaginal delivery of clotrimazole (CMZ). The solubility of CMZ in oils and surfactants was evaluated to identify components of the microemulsion. The ternary diagram was plotted to identify the area of microemulsion existence. Various gelling agents were evaluated for their potential to gel the CMZ microemulsion without affecting its structure. The bioadhesive potential and antifungal activity of the CMZ microemulsion-based gel (CMZ-MBG) was determined in comparison to the marketed clotrimazole gel (Candid-V gel) by in vitro methods. The chemical stability of CMZ in CMZ-MBG was determined as per the International Conference on Harmonization guidelines. The CMZ microemulsion exhibited globule size of 48.4 nm and polydispersity index of 0.75. Carbopol ETD 2020 could successfully gel the CMZ microemulsion without disturbing the structure. The CMZ-MBG showed significantly higher (P < 0.05) in vitro bioadhesion and antifungal activity as compared to that of Candid-V gel. The stability studies indicated that CMZ undergoes acidic pH-catalyzed degradation at all the storage conditions at the end of 3 months.

Gelation of microemulsions and release behavior of sodium salicylate from gelled microemulsions

A novel gelled microemulsion was prepared in the presence of the low molecular weight gelator N-stearine- N′-stearyl- l-phenylalanine at a very low concentration. It is completely different from the conventional microemulsion-based gels (MBGs) usually formed by polymeric gelling agents, such as gelatin, agar and κ-carrageenan. The microemulsion consists of i-propyl myristate, Tween 80, propylene glycol and water. The gelled microemulsions showed good thermo-reversibility. The gel-to-sol transition temperature ( T GS) of gelled microemulsion depends upon the concentration of gelator and the composition of the microemulsions. The gelation mechanism was investigated by polarized optical microscopy (POM) and FT-IR. POM images show elongated and strand-like crystallites formed by the aggregation of the gelator, ultimately resulting in the gelation of the microemulsion. FT-IR analysis indicates that intermolecular hydrogen bonds are responsible for the formation of gelator aggregates. Water-soluble sodium salicylate was used as a model drug for the investigation of the release from the gelled microemulsions. The release profiles exhibited a controlled release and followed the first-order release kinetics. The release rates decreased with an increase of the gelator and isopropyl myristate contents. These results reveal potential applications of gelled microemulsion in drug delivery systems.

Pluronic lecithin organogel

The purpose of this review is to give detail insight of pluronic lecithin organogels (PLOs) as a topical and transdermal drug delivery system. Pluronic lecithin organogel is a microemulsion-based gel that has been effectively used by physicians and pharmacists to deliver hydrophilic and lipophilic drugs topically and transdermally across the stratum corneum. It is thermodynamically stable, viscoelastic, and biocompatible gel composed of phospholipids (lecithin), organic solvent, and polar solvent. Various types of therapeutic agents have been easily incorporated in PLO to improve their topical drug delivery. Pluronic lecithin organogel improves the topical administration of drug mainly because of desired drug partitioning, biphasic drug solubility, and the modification of skin barrier system by organogel components. Beside this, it shows low skin irritation, increases patient compliance, reduces side effects, avoids first pass metabolism, and increases efficiency of drug. In addition, PLO has been shown in vivo and in vitro to modulate the release and permeation of drugs applied transdermally. Thus, in future, it has wide range of applications and opportunities to experiment with various drugs in this type of drug delivery system.

Activity and Enantioselectivity of Lipase Immobilized in CTAB Microemulsion-based Gels

Activity and Enantioselectivity of Lipase Immobilized in CTAB Microemulsion-based Gels

Preparation of temperature-sensitive microemulsion-based gels formed from a triblock copolymer

Temperature-sensitive microemulsion-based gels (MBGs) of Pluronic F127 (PEO 99–PPO 67–PEO 99) were formed in microemulsion systems composed of isopropyl myristate (IPM)/Span20/Tween20/H 2O, with or without a model drug (chloramphenicol), and the phase behaviors of the systems were investigated. The viscoelastic properties and gelation temperatures of the systems were characterized by rheological measurements. Effects of the concentration of F127 and the model drug (chloramphenicol) on the viscoelastic properties and gelation temperatures were also studied. It was observed that the viscosities of the gels increased and the gelation temperatures decreased with increasing F127 concentration. Chloramphenicol had little effect on the viscosities and gelation temperatures of the MBG. Moreover, chloramphenicol was sustainably released from the MBG system. Freeze-fracture transmission electron microscopy (FF-TEM) demonstrated that the amphiphilic triblock copolymer (F127) self-assembled in the selected microemulsion system and formed network structures. The microstructures of the microemulsion droplets were maintained in the MBG after the addition of F127. The results of fluorescence spectroscopy also supported this conclusion. Based on these results, a plausible schematic model was proposed to explain the mechanism of MBG formation.

Removal of chromate from water by a new CTAB–silica gelatin composite

A novel composite able to remove hexavalent chromium Cr(VI) from aqueous solutions was obtained by adding the silica precursor tetraethoxysilane (TEOS) to the hexadecyltrimethylammonium bromide (CTAB) microemulsion-based gel. A physical characterization of the new matrix revealed high stability of the silica gelatin composite in water at high temperatures and at neutral pH. Good efficiency in removing chromate from neutral solutions was also demonstrated by the adsorption kinetics. In particular, the adsorption data of chromate obtained with the CTAB–silica gelatin composite at 25 °C and pH 7.5 are described by the Freundlich isotherm model. The specific role of CTAB in the silica gelatin composite was also evaluated by comparing the kinetics of the anionic AOT–silica gelatin composite to the CTAB one. The data collected clearly showed that the positively charged surfactant was necessary to efficiently adsorb Cr(VI) from aqueous solutions. SEM and pulsed gradient spin–echo NMR analysis of the composite demonstrated that the silicon is well assembled in the gelatin network, in which water molecules maintain a high mobility. The diffusion coefficient of water in this system was shown to remain close to the value of pure water. Finally, X-ray analyses of the elemental content in the CTAB–silica gelatin composite indicated no difference in terms of percentage of silica distributions in different areas of the matrix and suggested that chromium adsorption could take place in internal areas.

Microemulsion as a vehicle for transdermal permeation of nimesulide

Topical microemulsions of nimesulide, a poorly water-soluble nonsteroidal antiinflammatory drug, using olive oil as oil phase and Tween 80/iso-octanol as surfactant/co-surfactant were designed. Various concentrations of surfactant: co-surfactant (2:1, 3:1, 4:1) were used in constructing a pseudoternary phase diagram. Oil-in-water microemulsions with ratio 15/35/50 (o/w/s) was chosen for the present study after evaluating various parameters like centrifugation, viscosity and stability. Using 4:1 ratio of surfactant : co-surfactant, a microemulsion-based gel of nimesulide was prepared with 1% Carbopol 934. In vitro permeation study of the gel was carried out through excised hairless rat skin and compared with a marketed preparation. The drug release after 24 h from the prepared microemulsion gel and marketed formulation was found to be 72% and 81% respectively. No significant difference was observed between the release rates of nimesulide from both formulations despite their differences in alcohol content. Microemulsion-based gel of poorly water-soluble nimesulide was successfully developed with in vitro release rates comparable to that of the marketed gel formulation.

Organogels in drug delivery

In the last decade, interest in physical organogels has grown rapidly with the discovery and synthesis of a very large number of diverse molecules, which can gel organic solvents at low concentrations. The gelator molecules immobilise large volumes of liquid following their self-assembly into a variety of aggregates such as rods, tubules, fibres and platelets. The many interesting properties of these gels, such as their thermoreversibility, have led to much excitement over their industrial applications. However, only a few organogels are currently being studied as drug/vaccine delivery vehicles as most of the existing organogels are composed of pharmaceutically unacceptable organic liquids and/or unacceptable/untested gelators. In this paper a brief overview of organogels is presented, followed by a more in-depth review of the gels that have been investigated for drug and/or vaccine delivery. These include microemulsion-based gels and lecithin gels (studied for transdermal delivery), sorbitan monostearate organogels and amphiphilogels (studied as vaccine adjuvants and for oral and transdermal drug delivery, respectively), gels composed of alanine derivatives (investigated as in situ forming gels) and Eudragit organogels (studied as a matrix for suppositories). Finally, pluronic lecithin organogels, descendents of lecithin gels but which are not really organogels, are briefly discussed for their interesting history, their root and the wide interest in these systems.

Gelatin Microemulsion-Based Gels with the Cationic Surfactant Cetyltrimethylammonium Bromide: A Self-Diffusion and Conductivity Study

In this contribution we demonstrate that gelatin can jellify also water-in-oil microemulsions based on the cationic surfactant cetyltrimethylammonium bromide (CTAB). The partial stability diagram of the system CTAB + 1-pentanol + water + hexane + gelatin was determined. The resulting microemulsion-based gels (MBGs) were characterized by means of conductivity and pulsed gradient spin-echo NMR. For the first time the water self-diffusion coefficient was measured in gelatin MBGs, and the results were successfully analyzed in terms of diffusion in an interconnected network of aqueous channels.

LECITHIN-STABILIZED MICROEMULSION-BASED ORGANOGELS FOR TOPICAL APPLICATION OF KETOROLAC TROMETHAMINE. II. IN VITRO RELEASE STUDY

Ketorolac tromethamine (KT) containing microemulsion-based gels (MBGs) have been formulated, based on the previous phase diagram studies, using a pharmaceutically acceptable surfactant (soybean lecithin; Epikuron 200) and oil (isopropyl myristate; IPM) and the effect of formulation variables on the release profile of the drug from MBGs through intact guinea pig skin and various artificial membranes was then determined experimentally. It was observed that as the lecithin concentration increased from 40 to 50 and then 60% w/w in formulations, a significant decrease in KT release was obtained. A remarkable increase in the drug release was also observed in formulations containing 6.5% w/w of KT compared to those containing 1% w/w of the drug. Increasing the water content of the organogels also resulted in an increase in KT release. The optimized formulation of the organogel composed of 40% lecithin and 60% IPM (containing 0.6% w/w of water and 6.5% w/w of KT) showed the highest drug release rate. Moreover, the viscosity of different formulations and their rheological behavior were also determined. All formulations showed a slightly rheopexic behavior. It was found that an increase in lecithin concentration resulted in an increase in the viscosity of the organogel. Results have shown that KT could be incorporated at high concentrations into lecithin organogels and these systems could be considered as desirable drug delivery vehicles for water soluble drugs and are capable of providing an appropriate drug release rate and pattern.

Transdermal Delivery of Nicardipine: An Approach to In Vitro Permeation Enhancement

Nicardipine hydrochloride (NC-HCl), a calcium channel blocker for the treatment of chronic stable angina and hypertension, seems to be a potential therapeutic transdermal system candidate, mainly due to its low dose, short half-life, and high first-pass metabolism. The objective of the present study was to evaluate its flux and elucidate mechanistic effects of formulation components on transdermal permeation of the drug through the skin. Solubility of NC-HCl in different solvent systems was determined using a validated HPLC method. The solubility of drug in various solvent systems was found to be in decreasing order as propylene glycol (PG)/oleic acid (OA)/dimethyl isosorbide (DMI) (80:10:10 v/v) > PG > PG/OA (90:10 v/v) > polyethylene glycol 300 > ethanol/PG (70:30 w/w) > transcutol > dimethyl isosorbide (DMI) > ethanol > water and buffer 4.7 > 2-propanol. Propylene glycol was then selected as the main vehicle in the development of a transdermal product. As a preliminary step to develop a transdermal delivery system, vehicle effect on the percutaneous absorption of NC-HCl was determined using the excised skin of a hairless guinea pig. Vehicles investigated included pure solvents alone and their selected blends, chosen based on the solubility results. In vitro permeation data were collected at 37°C, using Franz diffusion cells. The skin permeation was then evaluated by measuring the steady state permeation rate (flux) of NC-HCl, lag time, and the permeability constant. The results showed that no individual solvent was capable of promoting NC-HCl penetration. Permeation profiles of the drug through hairless guinea pig skin using saturated solutions of drug were constructed. Among the systems studied, the ternary mixture of PG/OA/DMI and binary mixture of PG/OA showed excellent flux. The flux value of the ternary system was nearly three times higher than the corresponding values obtained for the binary solvent. A similar trend also was observed for the permeation conture stant, while the values of lag time were reversed. The ternary mixindicated was then selected as a potential absorption enhancement vehicle for the transdermal delivery of drug. In general, higher fluxes were observed through hairless guinea pig skin as compared with the human stratum corneum. Based on the results obtained from the release study of NC-HCl from saturated solutions of the drug, a novel lecithin organogel (microemulsion-based gel) composed of soybean lecithin, propylene glycol, oleic acid, dimethyl isosorbide, and isopropyl myristate was developed as a possible matrix for transdermal delivery of NC-HCl. In vitro percutaneous penetration studies from this newly developed gel system through giunea pig skin and human stratum corneum revealed that the organogel system has skin-enhancing potential and could be a promising matrix for the transdermal delivery of nicardipine. Furthermore, higher permeation rates were observed when nicardipine free base was incorporated into the gel matrix instead of hydrochloride salt.

Influence of Diffusion on the Kinetics of an Enzyme-Catalyzed Reaction in Gelatin-Based Gels

The influence of mass-transport limitations on the initial reaction rates of a lipase-catalyzed stereoselective esterification reaction has been investigated for two structurally different gelatin-based gels. The time to reach equilibrium is much longer in pelleted hydrogels (pseudo-solid aqueous gels; PAGs) than in pelleted microemulsion-based gels (MBGs). R/S-(±)-2-Octanol and hexanoic acid were used as substrates. The reaction takes place by imbibition of the substrate-containing organic solvent into pores of the pelleted gel. To minimize the diffusion distances, the macroscopic surface areas of the gels were increased by granulating the gel pellets. The experimentally obtained initial reaction rates in granules were in good agreement with the theoretically obtained values from extrapolation to infinitely large areas. However, the still low initial reaction rates in the hydrogels compared to those in microemulsion-based gels cannot be explained by diffusion limitations. This finding was supported by the similar activation energies in both gels in granulated form. Changes in apparent molar standard enthalpy, entropy, and Gibbs energy for the activated complex formation were also estimated. The low reaction rate in hydrogels might thus be due to partial denaturation of the enzyme during the preparation step, to higher surface energy, or to the influence of a different solvent environment on the enzyme in these gels than in the microemulsion-based gels.

Improved Drug Delivery Using Microemulsions: Rationale, Recent Progress, and New Horizons

Microemulsions are excellent candidates as potential drug delivery systems because of their improved drug solubilization, long shelf life, and ease of preparation and administration. The formulation of microemulsions for pharmaceutical use requires a thorough understanding of the properties, uses, and limitations of microemulsions. Three distinct microemulsions--oil external, water external, and middle phase--can be used for drug delivery, depending upon the type of drug and the site of action. In this article, we present an examination of microemulsions as drug carrier systems, starting with general information and moving to a thorough review of the microemulsion literature, with a special section devoted to microemulsion-based gels.

Organo-gel de heptano: diagrama de fases e aplicações sintéticas

The phase diagram formation of microemulsion-based gels composed of an anionic surfactant aerosol-OT sodium bis (2-ethylhexyl)-sulphosuccinate), water, gelatin and an organic solvent is presented for heptane. The stability of this organo- gel, when an enzyme is immobilized is discussed in terms of its reutilization in various esters synthesis.

Biocatalysis using microemulsion-based polymer gels containing lipase

Natural gelling agents such as gelatin, agar and κ-carrageenan have been tested for the formation of lecithin microemulsion-based gels as well as hydrogels (without surfactant and oil). The results presented in this work provide information concerning the utility of these solid gels as lipase immobilization matrices. It was found that lipase from Pseudomonas cepacia keeps its catalytic function after entrapment in the gels, catalyzing the esterification reaction of propanol with lauric acid in various hydrocarbons at room temperature. Various parameters which affect the lipase catalytic behavior such as the nature and the concentration of the gelling agent, as well as the concentration of the biocatalyst and the mole ratio of the substrates have been examined. High yields (80%) were obtained with agar and κ-carrageenan organogels in isooctane. The remaining lipase activity, in repeated syntheses was found to depend on the nature of the biopolymer used for the formation of the organogels. Gelatin and agar microemulsion-based gels showed the highest operational stability.

Enantioselective Esterification of 2-Methylpentanoic Acid Catalised via Immobilized Lipases in Chrysotile and Microemulsion-Based Gels

Immobilized lipases in chrysotile and microemulsion-based gel (MBG) or organogel were used in the resolution of racemic 2-methylpentanoic acid that is a valuable synthetic intermediate for the preparation of, among other compounds, a number of steriochemically pure insect pheromones.

Lipase-catalysed stereoselective esterifications using gelatin-based hydrogels

A hydrogel stable in an organic solvent has been developed. This pseudo-solid aqueous gel (PAG) consists of only native gelatin and water, and has been used for immobilization of enzymes. A relatively high amount of gelatin is required in order to obtain stable gels. PAGs containing the enzyme Candida antarctica lipase (SP 525) were successfully used in catalysing the esterification of R/ S-(±)-2-octanol and hexanoic acid in hexane. The conversions as well as the enantiomeric excess values of the product, R-(−)-2-octyl hexanoate, were high and comparable to those obtained with microemulsion-based gels. The PAGs containing immobilized lipase gave reproducible results and may be re-used several times. The gels are easy to prepare and use, non-toxic and biocompatible. The PAGs retain their integrity in organic solvents and may be used in preparative-scale synthesis of organic compounds.