Microemulsion-based Hydrogel Research Articles

Microemulsion-based topical hydrogels containing lemongrass leaf essential oil (Cymbopogon citratus (DC.) Stapf) and mango seed kernel extract (Mangifera indica Linn) for acne treatment: Preparation and in-vitro evaluations.

Current treatments for severe acne include combinations of synthetic anti-inflammatory and antibacterial drugs, which possess numerous side effects. Therefore, this study developed microemulsion-based hydrogel containing lemongrass leaf essential oil (Cymbopogon citratus (DC.) Stapf) and mango seed kernel extract (Mangifera indica Linn) as a potential natural therapy for inflammatory acne. To this end, the microemulsions were first prepared using pseudo-ternary phase diagrams with soybean oil and coconut oil, cremophor RH40, and PEG 400. The optimal formula could load 1% lemongrass oil and 10% mango extract, possessed a spherical droplet size of ~18.98 nm, a zeta potential of -5.56 mV, and a thermodynamic stability. Secondly, the microemulsion-based hydrogel was developed by simple mixing the optimal microemulsion in carbopol-940 hydrogel (3.5% w/w). The product showed a viscosity of ~3728 cPs, a pH of 5.4-6.2, a spreadability of ~24 cm, an in-vitro Franz-cell cumulative release rate of ~80% for polyphenol content and ~60% for citral within 12 h, and a good physicochemical stability of > 3 months. Thirdly, the skin compatibility/irritability of the microemulsion-based hydrogel was determined by the HET-CAM assay, which showed non-irritation level. Finally, the anti-inflammatory activities of the hydrogel, using heat-induced BSA denaturation assay and LPS-stimulated RAW 264.7 NO inhibition assay, was 4-times higher than that of the reference drug Klenzit-C® (adapalene and clindamycin gel). Moreover, the hydrogel possessed strong anti-biofilm activity in Cutibacterium acnes, comparable with Klenzit-C®. Conclusively, the microemulsion-based hydrogel containing lemongrass oil and mango seed extract demonstrated much potentials to be a promising natural drug for acne treatment.

Characterization and Animal Skin Irritations Investigation of Vemurafenib Microemulsion-Based Hydrogel Using Oily Ionic Liquid

Cutaneous melanoma accounts for a yearly mortality rate of 55,500 persons. The use of oral small-molecule kinase inhibitors, specifically targeting BRAFv600, has been licensed as the principal treatment strategy for managing both locally progressed and metastatic presentations of the condition. Approximately 30% of people on vemurafenib, a BRAFv600 inhibitor, have side effects when are taken orally. Objective: This research was attempted to develop a vemurafenib microemulsion by substituting conventional oil phases with ionic liquids (ILs). The microemulsions were created by dissolving vemurafenib in a combination of ionic liquid (1-Butyl-3-methylimidazolium hexafluorophosphate and 1-Octyl-3-methylimidazolium hexafluorophosphate) and surfactant (Triton x-100). Multiple tests were conducted to measure physical stability, pH determination, content homogeneity examination, and in vitro medicine release analysis. Four formulations of Vemurafenib microemulsions successfully met all criteria in the microemulsion characterisation and assessment tests. The droplet sizes in these microemulsions fell inside the range of microemulsions, which is less than 200 nm. They were then used to create microemulsion-based hydrogels, employing Carbamer 340 as a gelling agent by conducting a simple mixing method. Hydrogels formed from microemulsions containing 1-Octyl-3-methylimidazolium hexafluorophosphate demonstrated the ability to form clear hydrogels with desirable consistency. Regarding Ex-vivo permeability study and skin deposition the permeability profiles of GOT3 formula exhibits a permeability measurement of 33569± 344 mP.s at 6 rpm, whereas GOT4 demonstrates a permeability measurement of 54723± 380 mP.s at 6 rpm. During the skin irritation test, there was no apparent erythema and edema were observed when compared to the negative group. This may indicate that the designed microemulsion-based gel formulation demonstrates good biocompatibility with skin tissue. Topical delivery of vemurafenib is a promising route of drug administration to melanoma skin. Ionic liquids (ILs) have permeation-enhancing properties with either hydrophilic or lipophilic characteristics‎‎‎‎‎.

Preparation and characterization of vemurafenib microemulsion based hydrogel using surface active ionic liquid

Cancer is considered the second leading cause of death worldwide. Skin melanomas account for the highest mortality rate amongst all types of skin cancer. Systemic treatment with vemurafenib has a high rate of adverse effects, so attempts have been made to prepare a topical form of this drug. Microemulsions have been used to improve drug delivery to the skin. The microemulsions were prepared by dissolving vemurafenib in a mixture of peppermint oil and Smix, followed by the addition of water. The characteristics and effectiveness of surface-active ionic liquid-based vemurafenib microemulsions were characterised and evaluated in vitro. The vemurafenib microemulsions (CP5, CP7 and CP8) had droplet sizes in the microemulsion range (less than 200 nm), and they were used to prepare microemulsion-based hydrogels using HPMC K15M via the hot and cold method. The prepared microemulsion-based hydrogels were then evaluated. The microemulsion-based hydrogel GP5 exhibited higher skin deposition (45.4%) than the other hydrogels; thus, GP5 is a promising candidate for the topical treatment of melanoma by vemurafenib.

KLVFF Conjugated Curcumin Microemulsion-Based Hydrogel for Transnasal Route: Formulation Development, Optimization, Physicochemical Characterization, and Ex Vivo Evaluation.

Curcumin is a potent natural compound used to treat Alzheimer's disease (AD). However, the clinical usefulness of curcumin to treat AD is restricted by its low oral bioavailability and difficulty permeating the blood-brain barrier. To overcome such drawbacks, various alternative strategies have been explored, including the transnasal route. However, rapid mucociliary clearance in the nasal cavity is a major hindrance to drug delivery. Thus, designing a delivery system for curcumin to lengthen the contact period between the drug and nasal mucosa must be employed. This study describes the optimization of KLVFF conjugated curcumin microemulsion-base hydrogel (KCMEG) to formulate a prototype transnasal preparation using the response surface method to improve a mucoadhesive property. A central composite design was employed to optimize and evaluate two influencing factors: the concentration of carbopol 940 and the percentage of KLVFF conjugated curcumin microemulsion (KCME). The physicochemical properties, anti-cholinesterase activity, and anti-aggregation activities of KCME were investigated in this study. The studied factors, in terms of main and interaction effects, significantly (p < 0.05) influenced hardness and adhesiveness. The optimized KCMEG was evaluated for pH, spreadability, and mucoadhesive properties. Ex vivo nasal ciliotoxicity to optimize KCMEG was performed through the porcine nasal mucosa. KCME was transparent, with a mean globule size of 70.8 ± 3.4 nm and a pH of 5.80 ± 0.02. The optimized KCMEG containing 2% carbopol 940 showed higher in vitro mucoadhesive potential (9.67 ± 0.13 min) compared with microemulsion and was also found to be free from nasal ciliotoxicity during histopathologic evaluation of the porcine nasal mucosa. The result revealed that both the concentration of carbopol 940 and the percentage of KCME play a crucial role in mucoadhesive properties. In conclusion, incorporating a mucoadhesive agent in a microemulsion can increase the retention time of the formulation, leading to enhanced brain delivery of the drug. Findings from the investigation revealed that KCMEG has the potential to constitute a promising approach to treating AD via transnasal administration.

Formulation of ibuprofen-loaded microemulsion-based hydrogel for topical administration

Background: Ibuprofen (IBU) is a nonsteroidal anti-inflammatory drug used to relieve pain and inflammation. Topical formulations of IBU can reduce unwanted side effects and first-pass metabolism in the liver. To enhance its water-poor solubility and permeability for topical administration, this study aimed to develop and characterise hydrogels containing IBU microemulsion. Materials and methods:Pseudo-ternary phase diagrams were constructed based on the evaluation of IBU solubility and the ratio of different excipients in the microemulsion formula. IBU microemulsion and IBU microemulsion-loaded hydrogels were characterised in terms of particle size and drug content by the high-performance liquid chromatography method. Ex vivo drug release through pig ear skin was evaluated using Hanson Research equipment. Results: The 1% xanthan gum hydrogel formula containing 5% (w/w) IBU microemulsion included 12.5% capryol 90, 33.33% acrysol K140, 16.67% propylene glycol and water (up to 100%, w/w) had a particle size of 25.69±2.12 nm and a polydispersity index of 0.226±0.095. The permeated drug percentage through the pig ear skin of the 1% xanthan gum hydrogel formula containing 5% (w/w) IBU microemulsion was 45-fold greater than that containing IBU material. Conclusion: These results showed that IBU-loaded microemulsion-based hydrogel would be a promising drug delivery system for topical administration.

Development and Characterization of Adapalene Loaded Microemulsion-Based Hydrogel for Acne Treatment Adapalene Microemulsion

Presently, acne is affecting globally many people (9.4%) and one of the leading causes of stress especially in youths. Adapalene (AD) has been applied successfully for acne treatment. However, adapalene drug is from BCS class II and exhibits less solubility in water (&lt;1mg/mL) &amp; causes skin irritation which leads to patient incompliance. The objective of the current study was design of microemulsion-based gel for topical delivery of adapalene. Solubility studies demonstrated that adapalene exhibit good solubility in Tween 80, propylene glycol, and oleic acid. The microemulsion showed globule size 248.4±2 nm, PDI (0.251), and Zeta potential (-15.8 mV) confirming colloidal stability. The dilutability and freeze-thaw study of microemulsion showed no sign of phase separation. The microemulsion-based gel showed clarity, pH (5±0.5), viscosity (64cps), and good spreadability (6.5±0.6 cm) for topical application. In-vitro gel formation study showed that inclusion of polymer (Carbopol 940) maintained viscosity of microemulsion-based hydrogel for longer period of time. Dissolution study demonstrated that AD showed sustained release for 24h from gel as compared to microemulsion and drug suspension. Thus, it could be a prospective formulation for acne treatment via topical route which can improve patient compliance by reducing skin irritation.

Superiority of microemulsion-based hydrogel for non-steroidal anti-inflammatory drug transdermal delivery: a comparative safety and anti-nociceptive efficacy study

Non-steroidal anti-inflammatory drugs (NSAIDs) represent the foundation of pain management caused by inflammatory disorders. Nevertheless, their oral administration induces several side effects exemplified by gastric ulceration, thus, delivering NSAIDs via skin has become an attractive alternative. Herein, microemulsion-based hydrogel (MBH), proliposomal, and cubosomal gels were fabricated, loaded with diclofenac, and physicochemically characterized. The size, charge, surface morphology, and the state of diclofenac within the reconstituted gels were also addressed. The ex-vivo permeation study using Franz cells was performed via the rat abdominal skin. The formulations were assessed in-vivo on mice skin for their irritation effect and their anti-nociceptive efficacy through tail-flick test. Biosafety study of the optimal gel was also pointed out. The gels and their dispersion forms displayed accepted physicochemical properties. Diclofenac was released in a prolonged manner from the prepared gels. MBH revealed a significantly higher skin permeation and the foremost results regarding in-vivo assessment where no skin irritation or altered histopathological features were observed. MBH further induced a significant anti-nociceptive effect during the tail-flick test with a lower tendency to evoke systemic toxicity. Therefore, limonene-containing microemulsion hydrogel is a promising lipid-based vehicle to treat pain with superior safety and therapeutic efficacy.

Gellan Gum Hydrogels Filled Edible Oil Microemulsion for Biomedical Materials: Phase Diagram, Mechanical Behavior, and In Vivo Studies.

The demand for wound care products, especially advanced and active wound care products is huge. In this study, gellan gum (GG) and virgin coconut oil (VCO) were utilized to develop microemulsion-based hydrogel for wound dressing materials. A ternary phase diagram was constructed to obtain an optimized ratio of VCO, water, and surfactant to produce VCO microemulsion. The VCO microemulsion was incorporated into gellan gum (GG) hydrogel (GVCO) and their chemical interaction, mechanical performance, physical properties, and thermal behavior were examined. The stress-at-break (σ) and Young’s modulus (YM) of GVCO hydrogel films were increased along with thermal behavior with the inclusion of VCO microemulsion. The swelling degree of GVCO hydrogel decreased as the VCO microemulsion increased and the water vapor transmission rate of GVCO hydrogels was comparable to commercial dressing in the range of 332–391 g m−2 d−1. The qualitative antibacterial activities do not show any inhibition against Gram-negative (Escherichia coli and Klebsiella pneumoniae) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria. In vivo studies on Sprague–Dawley rats show the wound contraction of GVCO hydrogel is best (95 ± 2%) after the 14th day compared to a commercial dressing of Smith and Nephew Opsite post-op waterproof dressing, and this result is supported by the ultrasound images of wound skin and histological evaluation of the wound. The findings suggest that GVCO hydrogel has the potential to be developed as a biomedical material.

Development of rivaroxaban microemulsion-based hydrogel for transdermal treatment and prevention of venous thromboembolism

We have developed a microemulsion (ME)-based hydrogel, containing propylene glycol, Azone®, Labrasol®, isobutanol and water (20:3:18:3:56), for the transdermal delivery of rivaroxaban (RVX). Formulation ME-1:RVX, which was loaded with 0.3 mg/g of RVX, presented as a clear, homogenous fluid with a droplet size of 82.01 ± 6.32 nm and a PdI of 0.207 ± 0.01. To provide gelation properties, 20 % (w/w) of Pluronic® F-127 was added to ME-1:RVX to generate formulation PME-1a. An added benefit was an increased capacity for RVX to 0.4 mg/g (formulation PME-1b). PME-1b displayed spherical droplets with a nanoscale diameter as observed by Transmission Electron Microscopy. The release of RVX from PME-1b was 20.71 ± 0.76 μg/cm2 with a permeation through pig epidermis of 18.32 ± 8.87 μg/cm2 as measured in a Franz Cell for 24 h. PME-1b presented a pseudoplastic behavior, pH value compatible with the skin and good stability over 60 days at room and elevated temperatures. The prothrombin time was assessed for each concentration of RVX obtained in the permeation assay and each demonstrated a relevant anticoagulant activity. PME-1b also presented no cytotoxicity against HaCaT cells. Utilizing GastroPlus® software, an in silico analysis was performed to simulate the delivery of PME-1b through a transdermal system that suggested a minimum dose of RVX for the treatment and prevention of venous thromboembolism could be achieved with an 8 h administration regimen. These results suggest that PME-1b is a promising transdermal formulation for the effective delivery of RVX that could be a viable alternative for the treatment and prevention of venous thromboembolism.

Design, optimization and evaluation of a microemulsion-based hydrogel with high malleability for enhanced transdermal delivery of levamisole

The objective of the present study was to prepare and evaluate a microemulsion-based hydrogel with high malleability as a transdermal delivery carrier for levamisole (LMS). A pseudo-ternary phase diagram and D-optimal mixture design were utilized to screen and optimize the microemulsion, and the formulation comprised 7.5% MaisineTM35-1, 33% Smix and 59.5% water. The microemulsion was physically stable with an average size of 19.3 ± 0.1 nm and zeta potential of −3.84 ± 0.05 mV. Moreover, a highly malleable alginate-boronic acid (alginate-BA) gel was prepared and could come into close contact with highly curved skin. The optimized microemulsion was loaded into alginate-BA gel and subjected to ex vivo and in vivo investigation. The microemulsion-based gel had desirable characterization, good stability and negligible skin irritation. The results of ex vivo permeation study showed that LMS achieved a significantly higher cumulative amount from the LMS-loaded microemulsion-based gel than that from the LMS-gel. The pharmacokinetic study showed a twofold increase in relative bioavailability compared to the commercial liniment. These results provide insight into the capability of the developed malleable microemulsion-based gel to enhance the transdermal permeation and bioavailability of LMS.

Formulation, clinical and histopathological assessment of microemulsion based hydrogel for UV protection of skin

The aim of this study was to prepare a microemulsion based hydrogel containing sesame oil and evaluate its topical application in preventing the harmful effects of UV radiation on the guinea pig's skin using histopathologic and clinical findings. Sesame oil with high antioxidant content and unique chemical and physiological properties is a suitable candidate for the evolution of UV protection on skin. Applying this natural oil in microemulsion formulation containing particles with nanometer size can enhance its efficacy. To prepare a stable microemulsion, it is necessary to select the appropriate surfactants. In this study, first the best combination of hydrophilic surfactant of Tween 80 with various lipophilic surfactants such as Span 20, Span 80 and Span 85 at different surfactant ratios was examined. The microemulsion formulations were assessed for particle size, zeta potential, polydispersity index, refractive index, electrical conductivity, pH value and stability. Results showed that among various samples, microemulsion containing a mixture of Tween 80 and Span 80 with the surfactant ratio of 9:1 was the best sample in terms of stability over time (six months). This sample had a lower particle size of 26.09 nm with a narrow particle size distribution. For topical application, the microemulsion based hydrogel was prepared with 0.6% Carbomer 940 as a gelling agent. The pH value and viscosity of gel formulation were 6.6 and 12.90 Pa.s, respectively, which is appropriate for topical applications. A slight enhancement of particle size inside hydrogel structure was observed after six months of the gel preparation. The clinical evolutions of formulation on guinea pig's skin were included skin scaling, skin irregularity, erythema, skin hyperpigmentation, and edema. Epidermal hyperkeratosis, hyperpigmentation, exocytosis, acanthosis, chromatin discoloration in nucleus of epidermal squamous cells, perifolliculitis, dermal vascular hyperemia, edema and dermal thickness, infiltration of plasma cell lymphocytes and eosinophils into dermis were observed for histopathological investigations. Based on clinical and histopathological examinations, topical application of microemulsion-based hydrogel of sesame oil can effectively prevent skin damage induced by UV radiation and is therefore suitable for skin products.

QbD based development and evaluation of topical microemulsion-based hydrogel against superficial fungal infections

Even though quality by design is becoming an essential method for a development of pharmaceutical product, limited studies have been performed to develop topical drug delivery systems. The aim of this study was to apply a quality by design approach to achieve predictable critical quality attributes of a microemulsion-based hydrogel formulation (MBH) contained itraconazole (ITZ). The control and response factors were determined based on a risk assessment with primary knowledge. Benzyl alcohol (x1), Cremophor® EL (x2), and Transcutol® P (x3) were screened out and selected as oil, surfactant, and co-surfactant, respectively. A D-optimal mixture design was used for optimizing the formulation with desirable characteristics. To obtain an optimal formulation, globule size was minimized, while viscosity and pH were in the range of 500–700 cps × 103 and pH 5–7, respectively. The optimal formulation was characterized by globule size, pH, rheological properties, in vitro permeability, and drug release simulation with a mathematical model. The optimal formulation was stable when stored at 40 °C/75% relative humidity and at ambient temperature for 6 months. Therefore, this study suggests that the optimized MBH formulation may present a better alternative over conventional ITZ delivery systems against superficial fungal infections.

Formulation of a microemulsion-based hydrogel containing celecoxib

The aims of this study are to prepare and characterize a microemulsion-based hydrogel containing celecoxib (CLX) for transdermal delivery. Pseudo-ternary phase diagrams containing 0.74% (w/w) CLX were constructed using a water titration method. The mixture exhibiting the largest area of the microemulsion region was selected. The effect of the ratio of oil to the mixture of surfactant and cosurfactant (O/Smix) on in vitro skin permeation was investigated. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to investigate the effects of the CLX microemulsion on skin. Rheological measurements were performed, and in vitro skin permeation of the CLX microemulsion-based hydrogel was tested. Based on pseudo-ternary phase diagrams, the Capryol PGMC-Tween 80-Transcutol P mixture was selected because it had the largest microemulsion area. A CLX microemulsion with O/Smix ratio of 3/7 was chosen because it had the greatest in vitro skin permeation. ATR-FTIR demonstrated that CLX microemulsion led to a transition in the alkyl chain of SC lipids and permeated hairless mouse dorsal skin. The CLX microemulsion-based hydrogel was elastic and suitable for application to skin. The incorporation of a gelling agent controlled the drug release of CLX, implying improved therapeutic effects of CLX for arthritis.

Microemulsion-based hydrogels for enhancing epidermal/dermal deposition of topically administered 20(S)-protopanaxadiol: in vitro and in vivo evaluation studies

Background20(S)-Protopanaxadiol (20S-PPD) is a fully deglycosylated ginsenoside metabolite and has potent dermal antiaging activity. However, because of its low aqueous solubility and large molecular size, a suitable formulation strategy is required to improve its solubility and skin permeability, thereby enhancing its skin deposition. Thus, we optimized microemulsion (ME)-based hydrogel (MEH) formulations for the topical delivery of 20S-PPD. MethodsMEs and MEHs were formulated and evaluated for their particle size distribution, morphology, drug loading capacity, and stability. Then, the deposition profiles of the selected 20S-PPD-loaded MEH formulation were studied using a hairless mouse skin model and Strat-M membrane as an artificial skin model. ResultsA Carbopol-based MEH system of 20S-PPD was successfully prepared with a mean droplet size of 110 nm and narrow size distribution. The formulation was stable for 56 d, and its viscosity was high enough for its topical application. It significantly enhanced the in vitro and in vivo skin deposition of 20S-PPD with no influence on its systemic absorption in hairless mice. Notably, it was found that the Strat-M membrane provided skin deposition data well correlated to those obtained from the in vitro and in vivo mouse skin studies on 20S-PPD (correlation coefficient r2 = 0.929‒0.947). ConclusionThe MEH formulation developed in this study could serve as an effective topical delivery system for poorly soluble ginsenosides and their deglycosylated metabolites, including 20S-PPD.

Co-delivery of evodiamine and rutaecarpine in a microemulsion-based hyaluronic acid hydrogel for enhanced analgesic effects on mouse pain models

The aim of this study was to improve the analgesic effect of evodiamine and rutaecarpine, using a microemulsion-based hydrogel (ME-Gel) as the transdermal co-delivery vehicle, and to assess hyaluronic acid as a hydrogel matrix for microemulsion entrapment. A microemulsion was formulated with ethyl oleate as the oil core to improve the solubility of the alkaloids and was loaded into a hyaluronic acid-structured hydrogel. Permeation-enhancing effects of the microemulsion enabled evodiamine and rutaecarpine in ME-Gel to achieve 2.60- and 2.59-fold higher transdermal fluxes compared with hydrogel control (p<0.01). The hyaluronic acid hydrogel-containing microemulsion exhibited good skin biocompatibility, whereas effective ME-Gel co-delivery of evodiamine and rutaecarpine through the skin enhanced the analgesic effect in mouse pain models compared with hydrogel. Notably, evodiamine and rutaecarpine administered using ME-Gel effectively down-regulated serum levels of prostaglandin E2, interleukin 6, and tumor necrosis factor α in formaldehyde-induced mouse pain models, possibly reflecting the improved transdermal permeability of ME-Gel co-delivered evodiamine and rutaecarpine, particularly with hyaluronic acid as the hydrogel matrix.

In vitro assessment of non-irritant microemulsified voriconazole hydrogel system

Research was aimed on microemulsion-based hydrogel for voriconazole. Oleic acid and isopropyl myristate as lipid phases; tween 20: tween 80 as surfactants and PEG600 as cosurfactant were selected to formulate voriconazole microemulsions. The promising microemulsions in terms of zeta potential, pH, viscosity, and drug release were selected and developed into hydrogels using carbopol 934. Resulting microemulsion-based hydrogel (MBH) of voriconazole were evaluated for in vitro diffusion and ex vivo permeation. Antifungal potentials of MBH were assessed against selected fungal strains. Optimal MBH formulations, O6 and O8 had displayed their antifungal potentials with enlarged zone of inhibition against selected fungal strains.

Microemulsion Based Hydrogel of Tacrolimus for the Treatment of Atopic Dermatitis

Objective: The aim of the present investigation was to develop microemulsionbased hydrogel of tacrolimus for topical application for the treatment of atopic dermatitis. Methods: Microemulsion containing tacrolimus was developed by water titration method and was successfully incorporated into freshly prepared 1% carbopol 940 gels. Preformulation studies such as preparation of standard curve by HPLC, solubility studies and construction of phase diagrams were carried out. Lauroglycol was selected as oil, Labrasol and Tween 80 (1:1) as surfactant blend and Transcutol P as co-surfactant, on the basis of solubility of tacrolimus in the above constituents. The optimized microemulsion formulation and microemulsion based hydrogel were characterized for various parameters and were evaluated for the efficiency to treat atopic dermatitis induced by 2,4-dinitrochlorobenzene in BALB/c mice. Results: The pH value and percent transmittance of microemulsion formulation were found to be 5.9 and 99.2%, respectively. Microemulsion did not show phase separation in centrifugation study. Transmission Electron Microscopy illustrated that the droplets of the microemulsion possessed spherical shape. The microemulsion based gel system possessed good spreadability and 83.31±1.148 % drug content. In vitro permeation studies showed that the permeation rate of both tacrolimus loaded microemulsions as well as microemulsion based hydrogel was observed to be higher than the drug solution and marketed ointment formulation. Histopathological analysis revealed that the microemulsion based hydrogel was more effective than the microemulsion and marketed ointment. Conclusion: The results indicated that the formulated microemulsion based hydrogel is promising vehicle for topical delivery of tacrolimus for the treatment of atopic dermatitis. Keywords: Microemulsion, microemulsion based hydrogel, tacrolimus, atopic dermatitis, topical delivery.

Preparation and evaluation of novel microemulsion-based hydrogels for dermal delivery of benzocaine

The purpose of the current research was to prepare and evaluate the potential use of microemulsion-based hydrogel (MBH) formulations for dermal delivery of benzocaine (BZN). The pseudoternary-phase diagrams were constructed for various microemulsions composed of isopropyl myristate (IPM) as oil phase, Span 20, Tween 20, Tween 80, cremophor EL and cremophor RH40 as surfactants, ethanol as cosurfactant and distilled water as aqueous phase. Finally, concentration of BZN in microemulsions was 2% (w/w). The physicochemical properties, such as conductivity, viscosity, pH, droplet size, polydispersity index and zeta potential of microemulsions, were measured. Carbopol 940 was used to convert BZN-loaded microemulsions into gel form without affecting their structure. Furthermore, excised rat abdominal skin was used to compare permeation and penetration properties of BZN loaded M3 and M3BHs with BZN solution. According to ex vivo study results, BZN-loaded M3BH1 showed highest flux values and high release rate values, and furthermore, this gel formulation had low surfactant content. Finally, in order to learn the localization of formulations within the dermal penetration, formulations and BZN solution were labeled with red oil O and subjected to fluorescence observation. In conclusion, BZN-loaded MBHs could be offered as a promising strategy for dermal drug delivery.

Development and evaluation of new microemulsion-based hydrogel formulations for topical delivery of fluconazole.

The aim of the present investigation was to develop and evaluate microemulsion-loaded hydrogels (MEHs) for the topical delivery of fluconazole (FZ). The solubility of FZ in oils, surfactants and cosurfactants was evaluated to identify the components of the microemulsion. The pseudo-ternary phase diagrams were constructed using the novel phase diagram by micro-plate dilution method. Carbopol EDT 2020 was used to convert FZ-loaded microemulsions into gel form without affecting their structure. The selected microemulsions were assessed for globule size, zeta potential and polidispersity index. Besides this, the microemulsion-loaded hydrogel (MEH) formulations were evaluated for drug content, pH, rheological properties and in vitro drug release through synthetic membrane and excised pig ear skin in comparison with a conventional hydrogel. The optimised MEH FZ formulations consisting of FZ 2%, Transcutol P 11.5% and 11%, respectively, as oil phase, Lansurf SML 20-propyleneglycol 52% and 50%, respectively, as surfactant-cosurfactant (2:1), Carbopol EDT 2020 1.5% as gelling agent and water 34.5% and 37%, respectively, showed highest flux values and high release rate values, and furthermore, they had low surfactant content. The in vitro FZ permeation through synthetic membrane and excised pig ear skin from the studied MEHs was best described by the zero-order and first-order models. Finally, the optimised MEH FZ formulations showed similar or slightly higher antifungal activity as compared to that of conventional hydrogel and Nizoral® cream, respectively. The results suggest the potential use of developed MEHs as vehicles for topical delivery of FZ, encouraging further in vitro and in vivo evaluation.

Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies.

BackgroundRotigotine is a potent and selective D1, D2, and D3 dopaminergic receptor agonist. Due to an extensive first-pass effect, it has a very low oral bioavailability (approximately 0.5% in rats).PurposeThe present investigation aimed to develop a microemulsion-based hydrogel for transdermal rotigotine delivery with lower application site reactions.MethodsPseudoternary phase diagrams were constructed to determine the region of oil in water (o/w)-type microemulsion. Central composite design was used to support the pseudoternary phase diagrams and to select homogeneous and stable microemulsions with an optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation experiments were performed, using Franz diffusion cells, to compare rotigotine-loaded microemulsions with rotigotine solutions in oil. The optimized formulation was used to prepare a microemulsion-based hydrogel, which was subjected to bioavailability and skin irritancy studies.ResultsThe selected formulations of rotigotine-loaded microemulsions had enhanced flux and permeation coefficients compared with rotigotine in oil. The optimum microemulsion contained 68% water, 6.8% Labrafil®, 13.44% Cremophor® RH40, 6.72% Labrasol®, and 5.04% Transcutol® HP; the drug-loading rate was 2%. To form a microemulsion gel, 1% Carbomer 1342 was added to the microemulsion. The bioavailability of the rotigotine-loaded microemulsion gel was 105.76%±20.52% with respect to the marketed rotigotine patch (Neupro®). The microemulsion gel irritated the skin less than Neupro.ConclusionA rotigotine microemulsion-based hydrogel was successfully developed, and an optimal formulation for drug delivery was identified. This product could improve patient compliance and have broad marketability.