Nanoemulsion Gel Research Articles

Development of Nanoemulsion Based Gel Loaded with Phytoconstituents for the Treatment of Urinary Tract Infection and in Vivo Biodistribution Studies.

Purpose: A nanoemulsion based gel containing Polyphenon 60 (P60) and cranberry (CRB) has been developed to deliver via intravaginal route for the treatment of urinary tract infection.Methods: Polyphenon 60 and cranberry were loaded in a single nanoemulsion gel (NBG) by ultra-sonication method and characterized for particle size, rheological properties, in vitro release and growth curve analysis. P60+CRB NBG were radiolabelled using technetium pertechnetate (99mTc) to perform in vivo pharmacokinetic studies in animals.Results: The finalized NE had a droplet size of 58±1 nm. In vitro release of 90.92 ± 0.6% in 8 hr for P60 and 99.39 ± 0.5% in 6 hr for CRB was observed in simulated vaginal fluid. Growth curve of E. coli indicated the inhibitory action of nanoemulsion based gel at the fifth hour of inoculation. Gamma scintigraphy studies on female Sprague-Dawley rats showed transport of nanoemulsion based gel from the vaginal cavity into the systemic circulation. Further, biodistribution studies with radiolabelled P60+CRB NBG showed significant higher uptake of radiolabelled actives by kidney (3.20±0.16) and urinary bladder (3.64±0.29), when administered intravaginally.Conclusion: The findings suggested 99mTc-P60+CRB NBG can potentially be transported through vaginal cavity and reach the target organs and showed effective distribution in organs affected in urinary tract infection

NANOEMULSION GEL OF NUTRACEUTICAL CO-ENZYME Q10 AS AN ALTERNATIVE TO CONVENTIONAL TOPICAL DELIVERY SYSTEM TO ENHANCE SKIN PERMEABILITY AND ANTI-WRINKLE EFFICIENCY

Objective: The object of our investigation was to develop and characterize nanoemulsion gel (NEG) as transdermal delivery systems for the poorly water soluble drug, Co-enzyme Q10 (CoQ10), to improve its solubility and skin permeability and thus improving its anti-wrinkle efficiency.Methods: An optimized nanoemulsion (NE) formula was chosen according to its particle size and stability and converted into nanoemulsion gel using different gelling agents, including; carbopol 934 (1%), xanthan gum (2%) and sodium carboxymethyl cellulose(NaCMC) (2%). Drug loaded nanoemulsion gels were characterized for particle size, zeta potential, viscosity and rheological behavior, conductivity, spreadability, drug content and permeation studies using Franz diffusion cell.Results: NEG containing 10% w/v isopropyl myristate (IPM) as oil, 60% w/v tween 80 and transcutol HP as surfactant/co-surfactant mixture (S/CoS), 30%w/v water, 2%w/v drug, and 1% w/v carbopol 934 as gelling gent was concluded as an optimized NEG formula. It exhibited pH, viscosity, drug content, particle size, zeta potential, polydispersity index(PDI) and spreadability, as 5.4±0.011, 27588±2034.34 cps,101.51±0.93%,120.5±1.19 nm,-29.8±1.46, 0.273 and 6.16±0.28 cm, respectively. Also, it showed significantly higher cumulative amount of drug permeated through dialysis membrane (281.71±0.97μg/cm2) and through rat skin (20.73±2.5 μg/cm2) than the other formulae and marketed formulation (P<0.001). In addition, its permeability parameters like drug flux (Jss), enhancement ratio (Er) and permeability coefficient (Kp) exhibited the highest values; 12.79µg/cm2/h, 95.92×10-4 cm2/h and 57.35, respectively for in vitro permeation study and 0.968µg/cm2/h, 7.26×10-4 cm2/h and 1.183, respectively for ex-vivo permeation study.Further histopathological evaluation test showed that CoQ10 NEG has a good anti-wrinkle efficacy compared to the conventional topical dosage form.Conclusion: These results judged NEG to be a promising alternative carrier for topical delivery of CoQ10 to enhance its solubility, skin permeability and thus anti-wrinkle efficiency.

STUDIES ON THE FORMULATION, PHYSICAL STABILITY, AND IN VITRO ANTIBACTERIAL ACTIVITY OF TEA TREE OIL (MELALEUCA ALTERNIFOLIA) NANOEMULSION GEL

Objective: This study aimed to formulate tea tree oil into a nanoemulsion gel dosage form and evaluate its physical stability and antibacterial activity.Methods: Nanoemulsion gels were formulated with various concentrations of tea tree oil, namely, 5%, 7%, and 9%, using Tween-80 as a surfactantand propylene glycol as a cosurfactant. The tea tree oil nanoemulsion gels showed a stable physical appearance over 8 weeks of storage at lowtemperature (4±2°C) and room temperature (25±2°C), cycling test, and centrifugation test.Results: The best formula was nanoemulsion gel formulation 1 (F1), which contained 5% tea tree oil, due to its good stability, smaller globule size,and greater viscosity. The results for antibacterial activity, determined by in vitro study, showed that the tea tree oil nanoemulsion gels exhibitedantibacterial activity against Propionibacterium acnes through the formation of an inhibition zone.Conclusion: Higher concentrations of tea tree oil in nanoemulsion gels (5%, 7%, and 9%) showed greater mean inhibition zones (28.33±0.88 mm,30.33±0.33 mm, and 31.67±0.33 mm, respectively).

PHYSICAL STABILITY AND ANTIOXIDANT ACTIVITY ASSAY OF A NANOEMULSION GEL FORMULATION CONTAINING TOCOTRIENOL

Objective: Tocotrienols have an antioxidant potential higher than that of tocopherols. Nanoemulsion gel can deliver tocotrienols into the skin toprevent skin damage caused by free radicals and improve the stability of the dosage form. The present study aimed to determine the physical stabilityand antioxidant activity of a nanoemulsion gel formulation containing tocotrienol.Methods: The tocotrienol nanoemulsion was made using tocotrienols, oleic acid, Tween 80, 96% ethanol, and propylene glycol. The gel base was madeusing a carbomer and triethanolamine. A physical stability test was conducted at three different temperatures, namely, low temperature (4±2°C),room temperature (27±2°C), and high temperature (40±2°C). The antioxidant activity was measured using the 2,2-diphenyl-1-picrylhydrazyl methodfor determining inhibitory concentration (IC50) values.Results: Formula 1 demonstrated the best physical stability, with a pH of 6.2. The droplet size of the tocotrienol nanoemulsion gel was 596 nm, witha zeta potential value of −27.1 nm. The IC50 of the tocotrienol nanoemulsion gel was 6252.14 ppm.Conclusion: The nanoemulsion gel formulation retained antioxidant activity and was physically stable for 8 weeks.

Appraisal of Transdermal Water-in-Oil Nanoemulgel of Selegiline HCl for the Effective Management of Parkinson's Disease: Pharmacodynamic, Pharmacokinetic, and Biochemical Investigations.

In the present study, the potential of transdermal nanoemulsion gel of selegiline hydrochloride for the treatment of Parkinson's disease was investigated. Water-in-oil nanoemulsions were developed by comparing low- and high-energy methods and were subjected to thermodynamic stability tests, in vitro permeation, and characterization studies. In vitro studies indicated that components of nanoemulsion acted as permeation enhancers with highest flux of 3.531±1.94μg/cm2/h from nanoemulsion SB6 containing 0.5mg selegiline hydrochloride, 3% distilled water, 21% S mix (Span 85, Tween 80, PEG 400), and 76% isopropyl myristate by weight. SB6 with the least droplet size of 183.4±0.35nm, polydispersity index of 0.42±0.06 with pH of 5.9±0.32 and viscosity of 22.42±0.14cps was converted to nanoemulsion gel NEGS4 (viscosity=22,200±400cps) by addition of Viscup160® for ease of application and evaluated for permeation, safety, and pharmacokinetic profile in Wistar rats. It provided enhancement ratio 3.69 times greater than conventional gel. NEGS4 showed 6.56 and 5.53 times increase in bioavailability in comparison to tablet and conventional gel, respectively, along with sustained effect. Therefore, the developed water-in-oil nanoemulsion gel promises to be an effective vehicle for transdermal delivery of selegiline hydrochloride.

Development of Curcumin loaded chitosan polymer based nanoemulsion gel: In vitro, ex vivo evaluation and in vivo wound healing studies

In the present study, various nanoemulsions were prepared using Labrafac PG+Triacetin as oil, Tween 80 as a surfactant and polyethylene glycol (PEG 400) as a co-surfactant. The developed nanoemulsions (NE1-NE5) were evaluated for physicochemical characterizations and ex-vivo for skin permeation and deposition studies. The highest skin deposition was observed for NE2 with 46.07% deposition amongst all developed nanoemulsions (NE1-NE5). Optimized nanoemulsion (NE2) had vesicle size of 84.032±0.023nm, viscosity 78.23±22.2 cps, refractive index 1.404. Nanoemulsion gel were developed by incorporation of optimized nanoemulsion (NE2) into 1–3% chitosan and characterized by physical evaluation and rheological studies. Chitosan gel (2%) was found to be suitable for gelation of nanoemulsion based on its consistency, feel and ease of spreadability. The flux of nanoemulsion gel was found 68.88μg/cm2/h as compared to NE2 (76.05μg/cm2/h) is significantly lower suggesting limited skin permeation of curcumin form gel. However, the retained amount of curcumin on skin by gel formulation (980.75±88μg) is significantly higher than NE2 (771.25±67μg). Enhanced skin permeation of NE2 (46.07%) was observed when compared to nanoemulsion gel (31.25%) and plain gel (11.47%). The outcome of this study evidently points out the potential of curcumin entrapped nanoemulsion gel in wound healing.

Nanoemulsion loaded gel for topical co-delivery of clobitasol propionate and calcipotriol in psoriasis

Current work reports the development and optimization of clobitasol propionate (CP) and calcipotriol (CT) loaded nanoemulsion based gel for topical treatment of psoriasis. Components of nanoemulsion viz., oil and surfactant/co-surfactant were selected depending upon solubility and emulsification potential respectively. The optimized ratio of 5:3:2 of Capmul MCM C8 EP, Cremophor RH 40 and Labrafil 1944 CS was selected. Carbopol 980 was used as gelling agent to achieve final drug concentration of 0.05% w/w and 0.005% w/w respectively for CP and CT. HaCaT cell lines showed higher uptake of drug from nanoemulsion in correlation with the enhancement in penetration of both drugs in stratum corneum (SC) and viable layer from nanoemulsion and gel as compared to free drugs. Imiquimod induced psoriatic BALB/c mice revealed significantly higher anti-psoriatic activity of nanoemulsion gel as compared to free drugs and marketed formulation. The developed formulation showed negligible skin irritation despite increased penetration into the skin.

Intravaginal Delivery of Polyphenon 60 and Curcumin Nanoemulsion Gel.

Polyphenon 60 (P60) and curcumin (CUR) were loaded in a single nanoemulsion system and their combined antibacterial action was studied against uropathogenic Escherichia coli. To enhance availability at target organs and to inhibit enzymatic degradation in gastro intestinal tract, vaginal route of administration was explored. P60 + CUR nanoemulsion (NE) was formulated by ultra-sonication and optimized using Box-Behnken design. Optimized NE showed Z-average of 211.2nm, polydispersity index of 0.343, and zeta potential of -32.7mV. Optimized P60+ CUR NE was characterized by stability testing and transmission electron microscopy, and it was observed that NE was stable at 4°C for 30days and monodisperse in nature with particle size of 195-205nm. P60+ CUR NE was further formulated as gel and characterized by viscosity, growth curve analysis, and in vitro permeation studies. In vitro drug permeation studies in simulated vaginal media showed maximum permeation (84 ± 0.21%) of curcumin within 5h and (91 ± 0.16%) of P60 within 8h. Both the drugs maintained sustained permeation for 12h. To investigate the transport via intravaginal route, gamma scintigraphy and biodistribution study of P60 + CUR NBG was performed on Sprague-Dawley rats using 99mtechnetium pertechnetate for radiolabeling to P60 molecule. Following intravaginal administration, P60 + CUR NBG dispersed in the kidney and urinary bladder with (3.07 ± 0.15) and (3.35 ± 0.45) percentage per gram after 3 h for P60 and CUR, respectively, and remained active for 12h. Scintigraphy images suggested that the P60 + CUR NBG given by intravaginal route led to effective distribution of actives in urinary tract, and this observation was in agreement with the biodistribution results.

Fabrication, in-vitro characterization, and enhanced in-vivo evaluation of carbopol-based nanoemulsion gel of apigenin for UV-induced skin carcinoma

The aim of this study was to develop a potential novel formulation of carbopol-based nanoemulsion gel containing apigenin using tamarind gum emulsifier which was having the smallest droplet size, the highest drug content, and a good physical stability for Skin delivery. Apigenin loaded nanoemulsion was prepared by high speed homogenization method and they were characterized with respect to morphology, zeta potential, differential scanning calorimeter study, and penetration studies. In-vitro release studies and skin permeation of apigenin loaded nanoemulsion by goat abdominal skin was determined using Franz diffusion cell and confocal laser scanning microscope (CLSM). The cytotoxicity of the reported formulation was evaluated in HaCaT Cells (A) and A431 cells (B) by MTT assay. The nanoemulsion formulation showed droplet size, polydispersity index, and zeta potential of 183.31 nm, 0.532, and 31.9 mV, respectively. The nanoemulsions were characterized by TEM demonstrated spherical droplets and FTIR to ensure the compatibility among its ingredients. CLSM showed uniform fluorescence intensity across the entire depth of skin in nanocarriers treatment, indicating high penetrability of nanoemulsion gel through goatskin. The nanoemulsion gel showed toxicity on melanoma (A341) in a concentration range of 0.4–2.0 mg/ml, but less toxicity toward HaCaT cells. The carbopol-based nanoemulsion gel formulation of apigenin possesses better penetrability across goatskin as compared to marketed formulation. Hence, the study postulates that the novel nanoemulsion gel of apigenin can be proved fruitful for the treatment of skin cancer in near future.

Rheological reversibility and long-term stability of repulsive and attractive nanoemulsion gels

The storage modulus (G′) of a canola oil nanoemulsion gel depends on the storage time and SDS emulsifier concentration.

Multiple particle tracking study of thermally-gelling nanoemulsions.

We perform multiple particle tracking (MPT) on a thermally-gelling oil-in-water nanoemulsion system. Carboxylated and plain polystyrene probes are used to investigate the role of colloidal probe size and surface chemistry on MPT in the nanoemulsion system. As temperature increases, hydrophobic groups of PEG-based gelators (PEGDA) partition into the oil/water interface and bridge droplets. This intercolloidal attraction generates a wide variety of microstructures consisting of droplet-rich and droplet-poor phases. By tailoring the MPT colloidal probe surface chemistry, we can control the residence of probes in each domain, thus allowing us to independently probe each phase. Our results show stark differences in probe dynamics in each domain. For certain conditions, the mean squared displacement (MSD) can differ by over four orders of magnitude for the same probe size but different surface chemistry. Carboxylated probe surface chemistries result in "slippery" probes while plain polystyrene probes appear to tether to the nanoemulsion gel network. We also observe probe hopping between pores in the gel for carboxylated probes. Our approach demonstrates that probes with different surface chemistries are useful in probing the local regions of a colloidal gel and allows the measurement of local properties within structurally heterogeneous hydrogels.

Enhancement of photoprotection potential of catechin loaded nanoemulsion gel against UVA induced oxidative stress

The present study was aimed to develop a catechin (CA) loaded nanoemulsion based nano-gel for the protection of skin against ultraviolet radiation (UV) induced photo-damage and to ensure its enhanced skin permeability as well as bioavailability through transdermal route. The optimized nanoemulsion (CA-NE4) was prepared by spontaneous nano-emulsification method. It was composed of oil (ethyl oleate), Smix [surfactant (span 80) and co-surfactant (transcutol CG)] and aqueous system in an appropriate ratio of 15:62:23% w/w respectively. The CA-NE4 was characterized through assessment of droplet size, zeta potential, refractive index, transmission electron microscopy (TEM), UV, high performance thin layer chromatography (HPTLC) and Fourier transform infrared spectroscopy (FTIR) analysis. The average droplet size and zeta potential of CA-NE4 were found to be 98.6±1.01nm and −27.3±0.20mV respectively. The enhanced skin permeability was better with CA-NE4 based nano-gel (CA-NG4) [96.62%] compared to conventional gel (CA-CG) [53.01%] for a period of 24h. The enhanced % relative bioavailability (F) of CA (894.73), Cmax (93.79±6.19ngmL−1), AUC0−t∞ (2653.99±515.02nghmL−1) and Tmax (12.05±0.02h) was significantly obtained with CA-NG4 as compared to oral suspension for extended periods (72h). CA-NG4 could improve the level of cutaneous antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) and reduce the level of thiobarbituric acid reactive substances (TBRAS) against oxidative stress induced by UVA. Nano-gel formulation of CA showed sustained release profile and enhanced photoprotection potential due to its improved permeability as well as bioavailability (P<0.05) compared to the conventional gel. Therefore, transdermal administration of nano-gel (CA-NG4) of CA offers a better way to develop the endogenous cutaneous protection system and thus could be an effective strategy for decreasing UV-induced oxidative damage in the skin tissues.

Enhancement of Anti-Dermatitis Potential of Clobetasol Propionate by DHA [Docosahexaenoic Acid] Rich Algal Oil Nanoemulsion Gel.

The aim of the present study was to investigate the potential of nanoemulsion formulation for topical delivery of Clobetasol propionate (CP) using algal oil (containing omega-3 fatty acids) as the oil phase. CP has anti-inflammatory, immunomodulatory and antiproliferative activities. However, its clinical use is restricted to some extent due to its poor permeability across the skin. Algal oil was used as the oil phase and was also exploited for its anti-inflammatory effect along with CP in the treatment of inflammation associated with dermatitis. Nanoemulsion formulations were prepared by aqueous phase titration method, using algal oil, tween 20, PEG 200 and water as the oil phase, surfactant, co-surfactant and aqueous phase respectively. Furthermore, different formulations were subjected to evaluate for ex-vivo permeation and in-vivo anti-inflammatory, irritation and contact dermatitis studies. The optimized nanoemulsion was converted into hydrogel-thickened nanoemulsion system (HTN) using carbopol 971 and had a viscosity of 97.57 ± 0.04 PaS. The optimized formulation had small average diameter (120 nm) with zeta potential of -37.01 mV which indicated good long-term stability. In-vivo anti-inflammatory activity indicated 84.55% and 41.04% inhibition of inflammation for drug loaded and placebo formulations respectively. The assessment of skin permeation was done by DSC and histopathology studies which indicated changes in the structure of epidermal membrane of skin. Contact dermatitis reveals that the higher NTPDase activity in the treatment with the CP-loaded nanoemulsion could be related to the higher anti-inflammatory effect in comparison with placebo nanoemulsion gel.

Unveiling the compatibility of eugenol with formulation excipients by systematic drug-excipient compatibility studies

The drug-excipient compatibility studies were carried out with the possible excipients viz. Tween 80, Carbopol 940, chitosan, sodium alginate, and polycaprolactone (PCL) for their possible use in the formulation of eugenol loaded nanoemulsion gels and nanoparticles. The eugenol-excipient compatibility studies were carried out by visual observations, differential scanning calorimetry (DSC), infrared spectroscopy (FTIR), and high-performance thin-layer chromatography (HPTLC). No notable change was observed in the samples on visual observation. From the results of the DSC studies, to a much extent, it was assumed that eugenol was not subjected to any interaction with the selected excipients for the proposed nanoemulsion gel and nanoparticles. But in some cases viz. polycaprolactone and Carbopol, though not to a significant level, slight deviation of the nature and position of the endothermic peaks of eugenol were observed. The results of the IR spectroscopy confirmed the compatibility of eugenol with Tween 80, Carbopol 940, chitosan, sodium alginate, and polycaprolactone. The retention factor of the HPTLC densitogram peaks for all the physical mixtures was well within the retention factor (Rf) value range observed for pure eugenol. The study results confirmed that eugenol is compatible with the selected excipients for the development of nanoemulsion gels and nanoparticles.

High-Performance Thin-Layer Chromatographic Analysis of Eugenol in Developed Nanoemulsion Gel and Nanoparticles: Validation of a Stability-Indicating Method

High-performance thin-layer chromatography (HPTLC) method for the quantification of eugenol from nanostructured drug delivery systems was successfully developed and validated. The mobile phase consisted of n-hexane:acetone (7:3, v/v), and the densitometric scanning was performed in the absorbance mode at 280 nm. The method was valid with respect to linearity and range, accuracy, precision, specificity, detection limit (DL), and quantitation limit (QL). The linearity of the method was established by a correlation coefficient value of 0.9930 ± 0.0013. The precision was tested by checking intra-day (repeatability) and inter-day (intermediate precision) variations. The method was established to be precise by low relative standard deviation (RSD) values for different concentration of eugenol. The results of the recovery studies of eugenol from preanalyzed samples demonstrated the accuracy of the method. The specificity of the developed method for the analysis of eugenol in the nanoemulsion gel and nanoparticle...

Curcumin-loaded colloidal carrier system: formulation optimization, mechanistic insight, ex vivo and in vivo evaluation.

The present work investigated the topical delivery potential of nanoemulsion gel loaded with curcumin (CR). CR nanoemulsion (CR-NE) was prepared by spontaneous emulsification method using oil (Labrafac PG/glyceryl triacetate), surfactant:cosurfactant (Smix) (tween 80/polyethylene glycol [PEG] 400) and water. The pseudo-ternary phase diagrams were constructed and thermodynamic stability testing was performed. Droplet size and zeta potential were evaluated using photon correlation spectroscopy and transmission electron spectroscopy. Six formulations selected with an average droplet size ≤70±2.72 nm showed a fourfold increase in skin permeation as compared to crude CR solution in oil. The formulation CR-NE4 having a flux of 117.04±2.32 µg/cm2/h and with maximum retention (42.87%) was selected, characterized (droplet size =41.13±3.34 nm and zeta potential =−33.1±1.45 mV), and incorporated into gel using carbopol-980 (1% w/v). Skin dynamics analyzed by confocal laser scanning microscopy showed maximum deposition of CR up to a depth of 86.98 µm and was in concordance with differential scanning calorimetry and Fourier transform infrared spectroscopy studies that confirmed lipid bilayer disruption, enhancing permeation. A 28-day anti-arthritic evaluation (body weight, paw edema, tibiotarsal joint thickness, TNF-α and IL-1β levels, and histopathology) on Freund’s complete adjuvant induced arthritic rat model after topical application of CR-NE gel in Wistar rats demonstrated substantial reversal of arthritic symptoms. Thus, CR-NE gel possesses potential for therapeutic effects locally in inflammatory arthritic disorders with improved topical bioavailability.

Accelerated Stability Studies of Atorvastatin Loaded Nanoemulsion Gel

Accelerated stability studies were carried out according to ICHQ1A (R2) guidelines. For drug products intended to be stored at room temperature, the accelerated stability studies are to be carried out at controlled temperature and humidity conditions of 40 ± 2°C and humidity 75 ± 5% RH. Results from stability studies indicated stability of atorvastatin loaded nanoemulsion gel formulation, as there was no significant change in observed physical parameters. The shelf life of nanoemulsion gel was found to be 19.23 months. The study conducted therefore substantiated the stability of atorvastatin loaded nanoemulsion gel.

Development of Tripterygium glycosides nano-carries based on "nanoemulsion-gels" and its pharmacodynamics

The aim of this study is to develop the Tripterygium glycosides nanoemulsion gels and investigate its pharmacodynamics. Oleic acid was used as oil phase, polyoxyethylene castor oil as surfaetant, and 1,2-propanediol as cosurfactant to screen the formula of Tripterygium glycoside nanoemulsion using the pseudo-temary phase diagrams. Then the nanoemulsion gels was prepared. The ICR mouse ears were sensitazated by 7% DNCB, and then were excited by 0.3% DNCB to stimulate the model of mouse chronic dermatitis and eczema. The concentrations of IFN-γ, IL-4 and IL-8 in mouse blood were determined by ELISA. The results showed that Tripterygium glycosides nanoemulsion gels could significantly inhibit the swelling of mouse ears(P < 0.01) and ameliorate the edama and erythema of model mouse ears skin. Also it could significantly decrease the expression of IFN-γ and IL-4 in model mouse blood. Tripterygium glycosides nanoemulsion gels had a good therapeutic effect on mouse model of dermatitis and eczema. It was expected to provide a new and long-acting exterernal preparation for the treatment of dermatitis and eczema.

Influence of emulsifier concentration on nanoemulsion gelation.

Nanoemulsion gels are a new class of soft materials that manifest stronger elasticity even at lower dispersed phase volume fraction. In this work, gelation in 40 wt % canola oil-in-water nanoemulsions was investigated as a function of emulsifier type (anionic sodium dodecyl sulfate (SDS) or nonionic Tween 20) and concentration. It was observed that the liquid nanoemulsions transformed into viscoelastic gels at a specific concentration range of SDS, whereas no gelation was observed for Tween 20. The apparent viscosity, yield stress, and storage modulus of the nanogels increased with SDS concentration until 15 times critical micelle concentration (CMC), thereafter decreased steadily as the gelation weakened beginning 20 CMC. Three regimes of colloidal interactions in the presence of emulsifier were proposed. (1) Repulsive gelation: at low SDS concentration (0.5-2 times CMC) the repulsive charge cloud around the nanodroplets acted as interfacial shell layer that significantly increased the effective volume fraction of the dispersed phase (ϕ(eff)). When ϕ(eff) became comparable to the volume fraction required for maximal random jamming, nanoemulsions formed elastic gels. (2) Attractive gelation: as the SDS concentration increased to 5-15 times CMC, ϕ(eff) dropped due to charge screening by more counterions from SDS, but depletion attractions generated by micelles in the continuous phase led to extensive droplet aggregation which immobilized the continuous phase leading to stronger gel formation. (3) Decline in gelation due to oscillatory structural forces (OSF): at very high SDS concentration (20-30 time CMC), structural forces were manifested due to the layered-structuring of excess micelles in the interdroplet regions resulting in loss of droplet aggregation. Tween 20 nanoemulsions, on the other hand, did not show repulsive gelation due to lack of charge cloud, while weak depletion attraction and early commencement of OSF regime leading to liquid-like behavior at all concentrations. The nanogels possess great potential for use in low-fat foods, pharmaceuticals and cosmetic products.

Preparation, characterization and stability study of dutasteride loaded nanoemulsion for treatment of benign prostatic hypertrophy.

Benign prostatic hyperplasia (BPH)is the most common condition in aging men, associated with lower urinary tract symptoms. It is caused due to the augmented levels of the androgen dihydrotestosterone. Dutasteride, a 5α-Reductase inhibitor has been recommended for the treatment of BPH upon oral administration. However, long term oral administration of dutasteride may cause sexual problem in man. Therefore the main objective of this study was to develop transdermal patch having nanoemulsion gel of dutasteride in order to enhance physical and chemical stability and eliminate adverse effect of dutasteride. Optimized nanoemulsion was prepared by aqueous phase-titration method and characterized by droplet size, viscosity and refractive index. In-vitro skin permeation of dutasteride through rat abdominal skin was determined by the Franz diffusion cell.Significant increase in the steady state flux (J ss), permeability coefficient (K p) and enhancement ratio (E r) was observed in optimized nanoemulsion formulation A1 (p < 0.05). The Er of optimized nanoemulsion A1 was found to be 1.52 times with respect to control which indicates transdermal delivery may be better approach for BPH. Stability studies were performed for the period of 3 months. It was found that droplet size, viscosity and refractive index were slightly increased at refrigerator and room temperature in 3 months period. However, the changes in these parameters were not statistically significant (p ≥ 0.05). The shelf-life of optimized nanoemulsion A1 was found to be 2.18 years at room temperature. These results indicated that both physical as well as chemical stability of dutasteride in nanoemulsion formulation.