Itraconazole-loaded microemulsions: formulation, characterization, and dermal delivery using shed snakeskin as the model membrane.

Microemulsions (MEs) were developed for dermal delivery of 1% w/w itraconazole (ITZ). Solubility of ITZ in various oils was investigated and clove oil was selected as oil phase. Pseudoternary phase diagrams were constructed by titration method. The system containing clove oil as oil phase, Tween®80 as surfactant, and 1:1 mixture of water and polyethylene glycol 400 as aqueous phase provided the largest ME region. It was selected for the formulation development of ITZ-loaded MEs. Physicochemical stability was evaluated at 4 °C, room temperature (25 °C), and 45 °C for three months. In vitro permeation and retention studies were assessed using shed snakeskin as a model membrane. Antifungal activity was investigated by agar diffusion method. Results indicated that incorporation of ITZ in the selected MEs did not affect physical properties. Physicochemical data after storage periods revealed that the most suitable storage temperature was 4 °C. Skin permeation and retention data indicated that water-in-oil (w/o) ITZ-loaded MEs had superior dermal delivery of ITZ than oil-in-water (o/w) ITZ-loaded ME and ITZ-oily solution. Moreover, w/o ITZ-loaded MEs showed larger inhibition zones against C. albicans and T. rubrum than a commercial gel. Therefore, w/o ITZ-loaded MEs possibly provided effective dermal delivery and antifungal activity to treat superficial fungal infections.

Stability and Release Kinetics of Natural Oil Microemulsions Containing Nicotinamide.

This research aimed to evaluate stability and release characteristics of nicotinamide-loaded microemulsions (MEs). Four MEs were prepared with Tween 80 as surfactant, Span 80 as cosurfactant, either virgin coconut oil or olive oil as oil phase, water as aqueous phase, and nicotinamide as an active ingredient. They were composed of 3% w/w nicotinamide and designated as MEC1-N, MEC2-N, MEO1-N, and MEO2-N. All samples were kept in clear glass containers at 4°C, room temperature (RT, 28° ± 2°C), and 45°C for 3 months. Afterward, they were observed for physical changes and analyzed for remaining nicotinamide by a validated high-performance liquid chromatography technique. MEC1-N and MEO1-N were compared for nicotinamide released through dialysis membrane using modified Franz diffusion cells. It was found that all samples were clear liquid and water-in-oil type. Phase separation was found in MEO2-N at all storage conditions. Discoloration was observed in all samples after being kept at 45°C for 3 months. MEC1-N, MEC2-N, and MEO1-N were both physically and chemically stable after being kept at 4°C and RT for 3 months. Release kinetics of MEC1-N and MEO1-N were the best fitted with the Higuchi model.

Optimization of nimesulide-loaded solid lipid nanoparticles (SLN) by factorial design, release profile and cytotoxicity in human Colon adenocarcinoma cell line.

The aim of this work is development of a nontoxic, long-term stable solid lipid nanoparticles (SLN) formulation for the loading of Nimesulide (NiM) by a 22 factorial design. The optimized formulation was composed of 10 wt% of glyceryl behenate and 2.5 wt% of poloxamer 188. Immediately after production, Z-Ave of NiM-SLN was 166.1 ± 0.114 nm, with a polydispersity index (PI) of 0.171 ± 0051 and zeta potential nearly neutral (-3.10 ± 0.166 mV). A slight increase of Z-Ave was recorded for NiM-SLN stored at 25 °C for a period of 15 days, whereas at 4 °C particles kept size within similar range. Long-term stability was monitored using TurbiscanLab®, showing a high stability of the nanoparticles with variations in the backscattering profiles below 10%. The release profile of NiM-SLN followed a sustained pattern with ca. 30% of drug released up to 24 h. Empty-SLN and NiM-SLN were nontoxic after exposing Caco-2 cells to the highest concentration (100 µg/mL) up to 48 hours (cell viability higher than 80%). NiM-SLN were lyophilized using different cryoprotectants, producing particles of 463.1 ± 36.63 nm (PI 0.491 ± 0.027) with 5% trehalose. Solid character of NiM-SLN was confirmed by DSC, recording a recrystallization index of 83% for NiM-SLN and of 74% for lyophilized SLN.

Lidocaine loaded gelatin/gelatinized tapioca starch films for buccal delivery and the irritancy evaluation using chick chorioallantoic membrane.

The aim of this study was to confirm the feasibility of gelatin/gelatinized tapioca starch (α st) films for buccal delivery and to evaluate their irritancy. Lidocaine (LB) and lidocaine hydrochloride (LH) were used as model drugs and glycerin was used as the plasticizer. The scanning electron microscopy, atomic force electron microscopy, X-ray diffraction and thermogravimetric analysis results confirmed the compatibility of gelatin/α st/glycerin (Gαgly) films. Drug releases of LB- or LH-Gαgly films were evaluated. The drug release profiles of medicated films presented good patterns in both short time and 8 h drug release studies. The permeation study was examined through chick chorioallantoic membrane (CAM) by using modified Franz diffusion cells. Moreover, the irritancy study for buccal films was also examined by a hen's egg test on CAM model (HET-CAM). The results revealed that LB and LH could permeate through CAM, and these Gαgly films created no irritation on HET-CAM. This indicates that the LB- and LH-Gαgly films are possible to use as buccal films.

Antidermatophytic Activity and Skin Retention of Clotrimazole Microemulsion and Microemulsion-Based Gel in Comparison to Conventional Cream.

AIM: Antifungal activity, skin permeation and skin retention of water-in-oil microemulsion (ME) and microemulsion-based gel (MBG) containing clotrimazole (CTZ) were evaluated in comparison to a conventional CTZ cream. METHODS: CTZ-ME and CTZ-MBG containing 1% w/w of CTZ were produced. Antifungal activity against Trichophyton mentagrophytes was assessed by the agar diffusion method. Pig skin was used in the in vitro penetration study using modified Franz diffusion cells. Drug amounts which permeated into the receptor fluid, retained in the skin membrane and remained in the donor compartment were analyzed by a validated HPLC technique. RESULTS: CTZ-ME and CTZ-MBG exhibited inhibition zones against T. mentagrophytes whereas the conventional cream did not reveal any inhibition zone in the assay. While no CTZ was detected in the receptor fluid up to 24 h following the in vitro penetration study from all tested formulations, the amount of CTZ retained in the skin membrane when applying CTZ-ME and CTZ-MBG was remarkably higher than that when applying the cream. CONCLUSION: Results revealed the capacity of ME and MBG in improving skin bioavailability of CTZ while reducing the risk of systemic side effects. Thereby, ME and MBG could increase the efficacy of CTZ for dermatophytosis treatment in comparison to conventional cream.

Evaluation of nicotinamide microemulsion on the skin penetration enhancement.

This study purposed to evaluate a microemulsion containing nicotinamide for its characteristics, stability, and skin penetration and retention comparing with a solution of nicotinamide in 2:1 mixture of water and isopropyl alcohol (IPA). The microemulsion system was composed of 1:1 mixture of Span80 and Tween80 as a surfactant mixture, isopropyl palmitate (IPP) as an oil phase, and 2:1 mixture of water and IPA as an aqueous phase. Nicotinamide microemulsion was prepared by dissolving the active in the aqueous phase before simply mixing with the other components. It was determined for its characteristics and stability under various conditions. The skin penetration and retention studies of nicotinamide microemulsion and solution were performed by modified Franz diffusion cells, using newborn pig skin as the membrane. The results showed that nicotinamide microemulsion could be obtained as clear yellowish liquid, was water-in-oil (w/o) type, possessed Newtonian flow, and exhibited physicochemical stability when kept at 4 °C and room temperature (≈30 ± 2 °C) during 3 months. From the skin penetration data, the microemulsion could enhance the skin penetration of nicotinamide comparing with the solution. Additionally, nicotinamide microemulsion could provide much higher amount of skin retention than that of skin penetration, resulting in suitability for a cosmeceutical product.

Transdermal nicotine mixed natural rubber-hydroxypropylmethylcellulose film forming systems for smoking cessation: in vitro evaluations.

Novel film forming polymeric dispersions for transdermal nicotine delivery were prepared from deproteinized natural rubber latex (DNRL) blended with hydroxypropylmethylcellulose (HPMC) and dibutyl phthalate (DBP) or glycerin (GLY) as plasticizer. The preliminary molecular compatibility of ingredients was observed by Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry characterizations. All film forming polymeric dispersions were elegant in appearance and smooth in texture without agglomeration. Their pH was 7-8. In addition, their viscosity and spreadability showed good characteristics depended on HPMC and plasticizers blended. The transparent in situ dry films with good strength and elasticity were also confirmed by peeling-off. The nicotine release from them revealed an initial fast release that was similar to the release from a concentrated nicotine solution, and followed by slow release pattern from the in situ films. GLY blended formulation produced a higher amount of nicotine permeation through the in vitro pig skin than DBP blends. Ethanol mixing also enhanced nicotine permeation, but it affected the integrity of in situ films. The nicotine release and skin permeation kinetics were by a diffusion mechanism that was confirmed by the Higuchi's model. These formulations were safe without producing any severe skin irritation. However, for the stability they needed to be stored at 4 °C in tightly sealed containers.

Formulation, physicochemical characterization, and in vitro study of chitosan/HPMC blends-based herbal blended patches.

The current work prepared chitosan/hydroxypropyl methylcellulose (HPMC) blends and studied the possibility of chitosan/HPMC blended patches for Zingiber cassumunar Roxb. The blended patches without/with crude Z. cassumunar oil were prepared by homogeneously mixing the 3.5% w/v of chitosan solution and 20% w/v of HPMC solution, and glycerine was used as plasticizer. Then, they were poured into Petri dish and produced the blended patches in hot air oven at 70 ± 2°C. The blended patches were tested and evaluated by the physicochemical properties: moisture uptake, swelling ratio, erosion, porosity, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction, and photographed the surface and cross-section morphology under SEM technique. Herbal blended patches were studied by the in vitro release and skin permeation of active compound D. The blended patches could absorb the moisture and became hydrated patches that occurred during the swelling of blended patches. They were eroded and increased by the number of porous channels to pass through out for active compound D. In addition, the blended patches indicated the compatibility of the blended ingredients and homogeneous smooth and compact. The blended patches made from chitosan/HPMC blends provide a controlled release and skin permeation behavior of compound D. Thus, the blended patches could be suitably used for herbal medicine application.

Deproteinized natural rubber film forming polymeric solutions for nicotine transdermal delivery.

Film forming polymeric solutions were prepared from DNRL blended with MC, PVA, or SAG, together with dibutylphthalate or glycerine used as plasticizers. These formulations were easily prepared by simple mixing. In a preliminary step, in situ films were prepared by solvent evaporation in a Petri-dish. Their mechanical and physicochemical properties were determined. The in vitro release and skin permeation of nicotine dissolved in these blended polymers were investigated by a modified Franz diffusion cell. The formulations had a white milky appearance, and were homogeneous and smooth in texture. Their pH was suitable for usage in skin contact. The mechanical property of in situ films depended on the ingredients but all compatible films were in an amorphous phase. The DNRL/PVA was shown to be the most suitable mixture to form completed films. The in vitro release and skin permeation studies demonstrated a biphasic release that provided an initial rapid release followed by a constant release rate that fitted the Higuchi's model. Nicotine loaded DNRL/PVA series were selected for the stability test for 3 months. These formulations needed to be kept at 4°C in tight fitting containers. In conclusion, film forming polymeric solutions could be developed for transdermal nicotine delivery systems.

Influence of talc and hydrogenated castor oil on the dissolution behavior of metformin-loaded pellets with acrylic-based sustained release coating.

Multi-unit pellet system (MUPS) is of great interest as it is amenable to customization. MUPS comprises multi-particulates, usually as pellets or spheroids, which can be coated with diffusion barrier coatings. One commonly used diffusion barrier coating is the methacrylic acid copolymer, which can be used as a taste masking, enteric or sustained release polymer. While the versatility of methacrylic acid copolymers makes them pliable for pellet coating, there are impediments associated with their use. Additives commonly required with this polymer, including plasticizer and anti-adherent, have been shown to weaken the film strength. The objective of this study was to investigate the impact of osmotic pressure within the core on the sustained release coat integrity and functionality. Hydrogenated castor oil (HCO) was chosen as the additive to be studied. Metformin-loaded pellets, prepared via extrusion-spheronization, were coated with ethyl acrylate and methyl methacrylate copolymer (Eudragit RS 30 D) containing talc, talc-HCO, or HCO to different coat thicknesses. Drug release was investigated using the USP dissolution apparatus 2 and an ultraviolet imager. The swelling of the pellets when wetted was monitored by video imaging through a microscope. When coated to 7.5 % coat weight gain, coats with HCO slowed down drug release more than the other pellets. The pellets also swelled the most, which suggests that they were more resistant to the osmotic pressure exerted by metformin. For drugs which exert high osmotic pressure, HCO can serve as an efficient alternative to talc in the preparation of methacrylic acid copolymer coatings.

Characterization and release kinetics of nicotinamide microemulsion-based gels.

The aim of this study was to investigate physicochemical characteristics and to determine in vitro release kinetics of prepared nicotinamide microemulsion-based gels (MBGs). Nicotinamide microemulsions (ME) were composed of 3% w/w nicotinamide, 7% w/w water, 25% w/w soybean oil, and 65% w/w of 9:1 oleth-10:isopropyl alcohol mixture. A water-in-oil (w/o) type ME was converted to three MBGs. ME was combined with 5% w/w of colloidal silica to obtain MBG-1, with 5% w/w of 0.5% w/w carbomer solution to obtain MBG-2, or with a mixture of 3% w/w of 0.5% w/w carbomer solution and 2% w/w of PEG-40 hydrogenated castor oil to obtain MBG-3. The results indicated that MBG-1 was a clear gel with plastic flow while MBG-2 and MBG-3 were turbid gels with Newtonian flow. MBG-1 was physically and chemically stable at 4°C as well as at ambient temperature (approximately 30°C) during the 2-month study period. The color darkened when stored at 60°C. The release kinetics of MBG-1 was best fitted to zero order model. The in vitro release of nicotinamide from MBG-1 through cellulose membrane was compared with that from the ME and an oil-in-water (o/w) commercial cream (CC). The rank order of release rate of nicotinamide from different formulations was MBG-1 > ME > CC.

N-acetylglucosamine microemulsions: Assessment of skin penetration, cytotoxicity, and anti-melanogenesis.

BACKGROUND: N-acetylglucosamine (NAG) is an amino sugar which can reduce melanin production. NAG has previously been formulated for topical use in many nanocarrier systems, excluding microemulsions (MEs). In this study, NAG was prepared in the form of MEs and assessed in terms of skin permeability, cytotoxicity, and effectiveness for cosmetic applications. AIMS: To investigate the skin penetration, cytotoxicity, and anti-melanogenesis of N-acetylglucosamine loaded microemulsions (NAG-MEs). METHODS: Two NAG-MEs (NME1 and NME2) were prepared. The in vitro penetration study of NAG-MEs was evaluated by modified Franz diffusion cells using full-thickness porcine ear skin as the membrane. The optimized formula was then selected for further assessment of cytotoxicity and efficiency. In vitro cytotoxicity was examined using human keratinocytes (HaCaT cells) and B16 melanoma cells. Anti-melanogenic activity was investigated by determination of melanin production of B16 melanoma cells. RESULTS: The cumulative amounts of NAG from NME1 and NME2 in the receptor fluid at 24 hours were 1010.46 ± 31.63 and 1260.99 ± 100.19 µg/cm2 and those accumulated in the skin membrane were 155.59 ± 19.19 and 181.11 ± 20.38 µg/cm2 , respectively. NME2 and its blank counterpart (Blank-ME2) showed no adverse effects on the viability of both HaCaT and B16 melanoma cells. The anti-melanogenic activity data showed that the NME2 treated B16 cells exhibited a significant melanin reduction. CONCLUSIONS: NAG-MEs could allow NAG penetrate through and accumulate in full-thickness porcine ear skin. NME2 was safe for both normal human keratinocytes and melanoma cells. It also showed effectiveness on anti-melanogenic activity in B16 melanoma cells.

Effect of Lipid and Oil Compositions on Physicochemical Properties and Photoprotection of Octyl Methoxycinnamate-loaded Nanostructured Lipid Carriers (NLC).

This study aimed to evaluate the effect of solid lipid and oil structures on the physicochemical properties, kinetic release, photostability, and photoprotection of nanostructured lipid carriers (NLC) containing octyl methoxycinnamate (OMC). OMC was used as a model compound since it is an effective sunscreen agent and is widely used in sunscreen products; however, it is unstable after ultraviolet radiation (UVR) exposure. OMC-loaded NLC were prepared from different solid lipids (cetyl palmitate (CP) or tristearin) and oils (caprylic/capric triglyceride, isopropyl myristate or isononyl isononanoate) at a 4:1 ratio. After production, the particle size (z-ave) and polydispersity index (PDI) of OMC-loaded NLC ranged from 190 to 260 nm and were lower than 0.25, respectively, and the zeta potential (ZP) values were higher than |50 mV|. The Fourier transform infrared (FTIR) spectroscopy results indicated no interaction among the components. Data obtained from differential scanning calorimetry (DSC) and X-ray diffraction showed that the incorporation of oil into solid lipids disturbed the crystallinity of the lipid matrix, depending on the structure of the oil molecule. OMC loaded in tristearin-based NLC (OMC-tristearin-NLC) showed higher release of OMC than OMC loaded in CP-based NLC (OMC-CP-NLC). For photostability properties, OMC-CP-NLC prepared from isononyl isononanoate showed the highest stability owing to the less-ordered structure, providing space for accommodation of OMC, whereas the percentage of OMC remaining in tristearin-based NLC was comparable. Therefore, the degree of protection was dependent on the type of solid lipid and oil. As a result, branched-chain fatty acids provided a higher degree of disturbance than linear-chain fatty acid.

Vesicular carriers containing phenylethyl resorcinol for topical delivery system; liposomes, transfersomes and invasomes.

Topical administration of phenylethyl resorcinol (PR) has attracted much attention as skin lightening agent with potent anti-tyrosinase activity. Two novel types of elastic carriers were developed to overcome the limitation of PR as topical delivery by increasing the solubility, stability and decreasing skin irritation compared to conventional liposomes. In addition, it also promotes skin penetration of PR to reach deep skin layer at the target site. The lead formulations were obtained from the invasomes containing 1% (w/v) d-limonene mixed with 10% (v/v) absolute ethanol as the skin enhancer, and transfersomes containing 15% (w/w) sodium deoxycholate (SDC) as edge activator. All formulations gave a vesicle size < 500 nm, polydispersity index (PDI) < 0.3, high zeta potential, entrapment efficiency > 50%, and good stability on storage at 30 °C at 75% RH for 4 months. Transfersomes have a lower degree of deformability (6.63%) than invasomes (25.26%). In contrast, the liposomes as rigid vesicles do not show a deformable property. This characteristic affects the skin permeation, and thus, transfersomes with high elastic property provided a significantly higher cumulative amount, steady state flux (J ss) and permeability coefficient (Kp ) compared to other formulations. However, in vitro PR accumulation in full-thickness newborn pig skin demonstrated that the application of elastic carrier formulations gave significantly higher accumulation than liposomes, and gave anti-tyrosinase activity up to 80%. These results are straightforwardly related to the results of cellular level study. Transfersomes and invasomes showed higher tyrosinase inhibition activity and melanin content reduction when compared to liposomes in B16 melanoma cells. In addition, acute irritation test in rabbits confirmed that these formulations are safe for skin application. Therefore, elastic vesicle carriers have the efficiency to deliver PR into the deep skin in both quantity and effectiveness which are better than conventional liposomes and appropriate for a skin lightening product.

Transdermal delivery of hydrophobic and hydrophilic local anesthetics from o/w and w/o Brij 97-based microemulsions.

PURPOSE: To characterize the physicochemical properties of drug-loaded oil-in-water (o/w) and water-in-oil (w/o) Brij 97-based microemulsions in comparison to their blank counterparts and to investigate the influence of microemulsion type on in vitro skin permeation of model hydrophobic drugs and their hydrophilic salts. METHODS: The microemulsion systems were composed of isopropyl palmitate (IPP), water and a 2:1 w/w mixture of Brij 97 and 1-butanol. The samples were characterized by visual appearance, pH, refractive index, electrical conductivity, viscosity and determination of the state of water and IPP in the formulations using differential scanning calorimetry (DSC). Transdermal flux of lidocaine, tetracaine, dibucaine and their respective hydrochloride salts through heat-separated human epidermis was investigated in vitro using modified Franz diffusion cells. RESULTS: The physicochemical properties of drug-loaded microemulsions and their blank counterparts were generally similar; however, slight changes in some physicochemical properties (apparent pH and conductivity) were observed due to the intrinsic properties of the drugs. The o/w microemulsions resulted in the highest flux of lidocaine, tetracaine and dibucaine as compared to the other formulations with in the same group of drugs. CONCLUSIONS: The characterization results showed that incorporation of the model drugs into the microemulsions did not change the microemulsion type. The permeation data exhibited that the nature of the microemulsions was a crucial parameter for transdermal drug delivery. The o/w microemulsions containing hydrophobic drugs provided the highest skin permeation enhancement. In addition, skin permeation was depended on the molecular weight of the model drugs.

The Optimized HPLC Method for Quantitative Analysis of Phenylethyl Resorcinol Loaded in the Novel Vesicle Carriers and Permeated in In Vitro Skin Permeation Study.

The high performance liquid chromatography (HPLC) was used for quantitative determination of phenylethyl resorcinol (PR) which was loaded in the novel vesicle carriers including ethosome, invasome and transfersome formulations, and permeated into pig skin membrane and receptor fluid for skin permeation study. The reverse-phase chromatography was carried out with a C18 column (150 × 4.6 mm2, 5 µm, HypersilTM, Thermo Fisher Scientific Inc, USA) with the column temperature at 25°C. A mixture of acetonitrile-methanol-Milli-Q water in the ratio of 40:20:40%, v/v/v was used as a mobile phase by maintaining the flow rate at 0.8 mL/min. The 20 µL sample solution was injected and the absorbance was detected at 254 nm using an HPLC Agilent 1100 series. This method gave the chromatogram with symmetric peak of PR at the appropriate retention time of 4.620 min. At such retention time no interfering peaks were detected from other matrix components. All %recovery and %RSD values of PR analysis were in the range of 98-102% and not more than 2.0%, respectively. From the validation data, the method demonstrated that it had satisfactory specificity, sensitivity, linearity, accuracy and precision appropriate for analysis of PR in the presence of vesicle carriers and skin permeation study.

Ethosomes of Phenylethyl Resorcinol as Vesicular Delivery System for Skin Lightening Applications.

Ethosome formulations containing phenylethyl resorcinol (PR) were developed. The formulation was produced from 0.5% w/v PR, 0.5% w/v cholesterol from lanolin, 3% w/v L-α-phosphatidylcholine from soybean, 30% v/v absolute ethanol, and water up to 100% v/v. It was characterized by a vesicular size of 389 nm, low polydispersity index of 0.266, zeta potential of -34.19 ± 0.44 mV, high PR entrapment efficiency of 71%, and good stability on storage at 4 and 30°C at 75% RH for 4 months. In vitro studies using pig skin revealed that permeation coefficient of PR from ethosomes was significantly higher than that from liposomes. In vitro retention profiles showed that PR accumulation in pig skin following application of ethosome formulations was 7.4-, 3.3-, and 1.8-fold higher than that achieved using liposomes, 20% propylene glycol solution, and 30% hydroethanolic solution, respectively. An inhibition value of around 80% was measured for antityrosinase activity of PR in pig skin. Consistently, ethosomes exhibited higher tyrosinase inhibition activity and melanin content reduction when compared to other formulations in B16 melanoma cells. Ethosomes did not cause acute dermal irritation in albino rabbits. These findings demonstrate that ethosomes are capable of delivering PR into the skin efficiently and hold promise for topical application of skin lightening products.

Clotrimazole microemulsion and microemulsion-based gel: evaluation of buccal drug delivery and irritancy using chick chorioallantoic membrane as the model.

OBJECTIVES: To investigate the efficacy of clotrimazole microemulsion (CTZ-ME) and its gel form, clotrimazole microemulsion-based gel (CTZ-MBG), for the treatment of oral candidiasis. METHODS: CTZ-ME and CTZ-MBG were characterized for droplet size and texture, respectively. The ex-vivo permeation study and irritancy assessment of CTZ-ME and CTZ-MBG were performed using chick chorioallantoic membrane (CAM) as the model. Antifungal activity against Candida albicans ATCC 10 231 of CTZ-ME and CTZ-MBG was determined by agar diffusion method compared to the blank counterparts. KEY FINDINGS: CTZ-ME contained nano-sized droplets and CTZ-MBG had acceptable firmness and spreadability. CTZ-ME exhibited faster CAM permeation of the drug and larger inhibition zone than CTZ-MBG as the increased viscosity of CTZ-MBG resulted in more retardation and higher fluctuations in drug diffusion. As there were no detectable visual changes in CAM blood vessels after applying CTZ-ME or CTZ-MBG, both formulations were non-irritants. CONCLUSIONS: CTZ-ME and CTZ-MBG could deliver the drug through CAM, the model for buccal delivery. Additionally, they did not cause irritancy and had effective antifungal activity against C. albicans. The results indicated that CTZ-ME and CTZ-MBG were potential effective antifungal formulations to treat oral candidiasis.

Characterization of microemulsion structures in the pseudoternary phase diagram of isopropyl palmitate/water/Brij 97:1-butanol.

This research was aimed to characterize microemulsion systems of isopropyl palmitate (IPP), water, and 2:1 Brij 97 and 1-butanol by different experimental techniques. A pseudoternary phase diagram was constructed using water titration method. At 45% wt/wt surfactant system, microemulsions containing various ratios of water and IPP were prepared and identified by electrical conductivity, viscosity, differential scanning calorimetry (DSC), cryo-field emission scanning electron microscopy (cryo-FESEM) and nuclear magnetic resonance (NMR). The results from conductivity and viscosity suggested a percolation transition from water-in-oil (water/oil) to oil-in-water (oil/water) microemulsions at 30% wt/wt water. From DSC results, the exothermic peak of water and the endothermic peak of IPP indicated that the transition of water/oil to oil/water microemulsions occurred at 30% wt/wt water. Cryo-FESEM photomicrographs revealed globular structures of microemulsions at higher than 15% wt/wt water. In addition, self-diffusion coefficients determined by NMR reflected that the diffusability of water increased at higher than 35% wt/wt water, while that of IPP was in reverse. Therefore, the results from all techniques are in good agreement and indicate that the water/oil and oil/water transition point occurred in the range of 30% to 35% wt/wt water.

Formation of microemulsions for using as cosmeceutical delivery systems: effects of various components and characteristics of some formulations.

Microemulsions are interesting formulations for cosmeceutical applications due to their good appearance, high solubilization power, thermodynamic stability, and enhancement of skin penetration. In addition, they can spontaneously form when suitable types and amounts of components are simply mixed. In this study, the phase behavior of the nonionic systems with various parameters was studied by construction of phase diagrams using titration method. Natural oils, i.e., coconut oil (CO), rice bran oil (RBO), and palm oil (PO), were analyzed for their fatty acid compositions and then mixed with blends of nonionic surfactants (Tween80: Span80) and water or mixtures of water and a cosolvent, propylene glycol (PG), to find the microemulsion regions. Subsequently, some microemulsions were selected for physical characterization. The largest microemulsion regions which were obtained from CO, RBO, and PO covered the sizes of 11.65, 9.84, and 9.24 %, respectively. The surfactant mixture at weight ratio of 1:1 was the most suitable for CO and PO, but for RBO, it was 2:1. PG could increase the microemulsion regions of PO from 9.24 to 15.33 %, depending on PG concentrations. Hence, the sizes of the microemulsion regions were related to oil types, surfactant mixtures, and ratios between water and PG. The studied microemulsions were water-in-oil (w/o) type, and their internal droplets were in the nanosize range. They exhibited Newtonian flow behavior and their mean viscosity values were from 247.53 to 690.35 cP which were correlated with the types and concentrations of the components in the formulations. In conclusion, natural oils could form w/o microemulsions with nonionic surfactants. The microemulsion formation and characteristics were related to many parameters of the components.