Pseudo-ternary Phase Diagrams Research Articles

FORMULATION AND EVALUATION OF LULICONAZOLE NANOEMULGEL USING BOX-BEHNKEN DESIGN APPROACH

Objective: The present study was aimed to develop and assess a Luliconazole-loaded nano emulgel for topical application. Methods: Nanoemulsion of Luliconazole was prepared by ultrasonication method. A pseudo-ternary phase diagram was constructed to determine the ideal ratio of oil and the surfactant/co-surfactant mixture for nanoemulsion preparation. The Box Behnken statistical design was utilized to optimize the nanoemulsion. The optimized batch of nanoemulsion was incorporated into the 1% Carbopol gel as nanoemulgel. It was evaluated for various parameters like globule size, zeta potential, pH, spreadability, viscosity, drug content, drug release, ex vivo permeation study, in vivo animal skin irritation study, and histopathology studies. Results: The optimized formulation showed a globule size of 130.5 nm and entrapment efficiency of 80% and the values were found to be within±5% of predicted values, indicating the suggested statistical model was significant at 95% of confidence interval. The zeta potential of the formulation was found to be-22.1 mV, indicating enhanced stability of the formulation. Transmission Electron Microscopy (TEM) images revealed that the formulation had a smooth surface texture with a mean globule size meeting the nanoscale size range. The drug release study demonstrated a sustained release pattern for the formulation, with a maximum release of 74.93±0.8% over 8 h. The formulated gel exhibited appreciable ex vivo permeability. An in vivo skin irritation test on Wister rats showed no signs of skin irritation from the formulation. The histopathological examination further confirmed that the formulation was dermatologically safe, exhibiting no toxicity or irritation. Conclusion: The results of the present study concluded that Luliconazole-loaded nanoemulgel could be a potential topical drug delivery approach for the management of fungal infections.

Artemisinin emulgel ameliorates cartilage degradation in knee osteoarthritis: in vitro and in vivo studies.

Aim: Laboratory scale-up of artemisinin-loaded emulgel (ART-emulgel) was carried out and characterized for therapeutic performance in osteoarthritis (OA).Materials & methods: The solubility of ART in various oils, surfactants and co-surfactants were screened for construction of pseudo ternary phase diagram (TPD), followed by scale-up of artemisinin loaded nanoemulsion (ART-NE). ART-NE was amalgamated with Carbopol Ultrez 10-NF to prepare ART-emulgel that was later characterized invitro and invivo to analyze therapeutic efficacy in monosodium-iodoacetate (MIA) induced knee OA.Results: The droplet diameter of ART-NE was estimated to be 104.3±2.593nm with a polydispersity index of 0.245±0.019 in addition to ζ-potential of 0.434±0.028mV. Steady-state flux and permeability coefficient for ART-emulgel were estimated to be 0.651±0.031 µg.cm2/h and 0.245±0.011cm/h, respectively. ART-emulgel demonstrated 43.18% reduction in COX-2 level; 52.28% drop in IL-1β, and 88.78% alleviation of Tumor Necrosis Factor-α (TNF-α) level when compared with monosodium-iodoacetate induced OA rats. ART-emulgel and injectable ART (intra-articular; I.A) portrayed minor synovial erosion compared with blank and diclofenac emulgel. Histopathological evidences indicated restoration of cartilage integrity followed by reduction of OARSI scores in ART-emulgel when compared with disease control animals.Conclusion: ART-emulgel is a potential dosage form for translating into a clinically viable product for the management of OA.

Development, Analysis, and Determination of Pharmacokinetic Properties of a Solid SMEDDS of Voriconazole for Enhanced Antifungal Therapy

Background: Voriconazole is an antifungal drug, which is classified under Bio-Classification System-II and has low water solubility (0.71 mg/mL) and high permeability. Hardly any endeavors have been made to increase the bioavailability of voriconazole. Objective: To develop and evaluate a solid SMEDDS (self-microemulsifying drug delivery system) for antifungal activity. Methods: Based on solubility studies of Labrafil-M 1994 CS (oil), Cremophor-RH 40 (a surfactant) and Transcutol-HP (a co-surfactant) were selected as components of the SMEDDS and a pseudo-ternary phase diagram was prepared. Thereafter, the oil, surfactant, and co-surfactant were mixed with altered weight ratios (1:1/1:2/2:1) and evaluated through various in vitro, in vivo analyses. Results: The particle size of the optimized formulation was observed to be 19.04 nm and the polydispersity index (PDI) value was found to be 0.162 with steady-state zeta potential. The optimized liquid SMEDDS was converted into a solid SMEDDS. Various adsorbents, such as Aerosil-200, Avicel-PH101, Neusilin-US2, and Neusilin UFL2 were screened to better detect the oil-absorbing capacity and flow properties of the powder. Neusilin UFL2 was selected as an adsorbent due to its better oil-absorbing capacity. DSC, X-ray diffraction, and dissolution studies were carried out to characterize the formulation. Further, the Pharmacokinetic profile was also studied in Wistar rats and the Cmax, tmax, and AUC0®t were calculated. The Cmax and AUC0®t plasma concentration is considerably better for the SMEDDS than for the pure drug and marketed formulation. Conclusions: This investigation clearly reveals the potential of developing a solid SMEDDS for candidiasis and invasive aspergillosis treatment, with better efficacy as compared to the commercially available marketed formulation.

DES/O microemulsion for solubilizing and delivering curcumin via the nasal administration to treat acute asthma

As a natural small molecule drug derived from turmeric, curcumin is known for its good biosafety and a range of beneficial effects, including anti-inflammatory, anti-spasmodic, antioxidant, antibacterial, anti-tumor, and neuroprotective effects. Even though, its insolubility in water and instability severely limit its bioavailability and clinical applications. The present study developed a deep eutectic solvent (DES) in oil microemulsion (DES/O-ME) system loaded with Cur for intranasal administration, aiming to enhance both the solubility and permeability of Cur to significantly increase its bioavailability. The project first constructed and screened the optimal choline chloride-based DES. Subsequently, the DES/O-ME system was prepared and optimized to achieve uniform particle size and stability using a pseudo-ternary phase diagram and electrical conductivity measurements. The resulting DES/O-ME system was thoroughly evaluated for its solubilization efficacy, permeability, mucosal cytotoxicity, and stability. Additionally, the therapeutic efficacy of the Cur-DES/O-ME was assessed in vivo using a murine model of allergic asthma. This comprehensive evaluation highlights the potential of the DES/O-ME system as a promising intranasal drug delivery platform to overcome the limitations of curcumin’s bioavailability and clinical application.

Development of a nanoemulsion containing Lippia origanoides essential oil with antifungal activity by low energy method: from extraction to formulation

The essential oil of Lippia origanoides is of great pharmacological interest because of a wide variety of attributes, in particular its antifungal action. Due to its low solubility in aqueous media, high volatility, and a high propensity for physicochemical degradation, the search for nanostructured systems to promote the stability of this phytocomplex is necessary. Nanoemulsion is an alternative method to stabilize and preserve this type of active ingredient, especially when generated by a low energy method and using Syagrus coronata (licuri) oil as an active carrier and stabilizer of this nanostructure. The objective of the present investigation was to formulate a stable nanoemulsion with Lippia origanoides essential oil carried through licuri oil with antifungal action by the low energy method. For this, we began with the extraction of the essential oil and the phytochemical characterization obtaining the chemotype B of this Lippia (carvacrol: 49.12%). Then, using the pseudoternary phase diagram, the optimal ratio of the oil phase 6:4 (essential oil: Syagrus coronata oil) was established, adding 15% of surfactant (polysorbate 80) and 75% of the aqueous phase. Then, with the formulated nanoemulsion, the physical-chemical characterization and evaluation of preliminary and accelerated stability were carried out. In addition, cytotoxicity, Franz cell permeation and antifungal activity against dermatophytes were evaluated. A stable nanoemulsion was obtained by the low energy method with the characteristic appearance of a nanoemulsion and a characteristic odor of essential oil. The average size of the nanoparticles was around 167.5 nm, narrow PDI (<0.2 nm), zeta potential below -10.0 mV, acidic pH (5.1), average conductivity 134.4 μSm/cm, refractive index characteristic of a translucent system and low viscosity (<6.0 mPa.S). Regarding cytotoxicity, it proved to be safe at dosages below 90 μg/mL, efficient in terms of permeation (76.7% in 24h) and effective in terms of antifungal activity as it had a minimum inhibitory concentration between 234.4/156.3 μg /mL and 11.2/7.5 μg/mL against the tested dermatophytes. In view of the results, a nanoemulsion containing the essential oil of L. origanoides carried by the oil of Syagrus coronata was shown to be a potential product for the topical treatment of fungal infections like dermatophytosis.

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.

Development of synergistic antifungal in situ gel of miconazole nitrate loaded microemulsion as a novel approach to treat vaginal candidiasis

Limited solubility is the main cause of the low local availability of anti-candidiasis drug, miconazole nitrate (MN). The study’s objective was to develop and characterize microemulsion (ME) based temperature-triggered in situ gel of MN for intravaginal administration to enhance local availability and antifungal activity. The solubility of MN was initially studied in different oils, surfactants, and co-surfactants. Then, pseudo-ternary phase diagrams were constructed to select the best ratio of various components. The ME formulations were characterized by thermodynamic study, droplet size, polydispersity index (PDI), viscosity, and in-vitro antifungal mean inhibition zone (MIZ). Selected MEs were incorporated into different in situ gel bases using a combination of two thermosensitive polymers (poloxamer (PLX) 407 and 188), with 0.6% of hydroxypropyl methylcellulose (HPMC K4M) and gellan gum (GG) as mucoadhesive polymer. ME-based gels (MG) were investigated for gelation temperature, gelation time, viscosity, spreadability, mucoadhesive strength, in vitro release profile, and MIZ test. Furthermore, the optimum MG was assessed for in vivo animal irritation test and FESEM investigation. Tea tree oil, lavender oil, tween 80, and propylene glycol (PG) were chosen for ME preparation for the optimal formulation; formulation ME7 and ME10 were chosen. After incorporation of the selected formulation into a mixture of P407 and P188 (18:2% w/w) with 0.6% mucoadhesive polymer, the resultant MG formulation (MG1) revealed optimum gelation temperature (33 ± 0.01℃) and appropriate viscosity with enhanced sustained release (98%) and retention through sheep vaginal mucosa, MG1 exhibited a better MIZ compared to the 2% MN gel formulation and the marketed MN product, and no rabbit vagina irritation. In conclusion, the miconazole nitrate-loaded MG-based formula sustained the duration of action and better antifungal activity than the marketed miconazole nitrate formulation.

Self-microemulsifying drug delivery system (SMEDDS) for oral delivery of zafirlukast: Design, formulation, and pharmacokinetic evaluation

The current research aimed to develop a self-microemulsifying drug delivery system (SMEDDS) of zafirlukast to enhance its oral bioavailability by increasing its solubility and overcoming the negative food effect. For the formulation of SMEDDS, the solubility of zafirlukast was determined in different oils, surfactants, and cosurfactants. Based on this study's results, pseudo-ternary phase diagrams were plotted to select the efficient self-emulsification region. Eudragit EPO was employed as a precipitation inhibitor to avoid the supersaturation of zafirlukast in the SMEDDS system. The formulated system was evaluated for transparency, cloud point, optical birefringence, and globule size analysis using techniques like DLS, SANS and TEM. The SMEDDS preconcentrate was solidified by adsorbing it on Neusilin US2 and further formulated as a tablet. It was then evaluated for in vitro drug release against the marketed tablet. The optimized composition of zafirlukast SMEDDS and suspension of the plain drug were evaluated for a pharmacokinetic profile in rats for both fed and fasted conditions. The SMEDDS yielded microemulsion found transparent and homogeneous with globule size less than 50 nm by DLS, SANS and TEM techniques. On dilution with water, the microemulsion was found robust without any phase separation even after 24 h of storage. The tablet form of SMEDDS was stable and passed all the IPQC tests for a tablet. The optimized SMEDDS tablet form exhibited a superior in vitro dissolution profile than a marketed tablet. The pharmacokinetic study of optimized SMEDDS showed improved value for Cmax and AUC in both fed and fasted conditions compared to the plain drug.

Self-Nanoemulsifying Drug Delivery System of Morin: A New Approach for Combating Acute Alcohol Intoxication.

Acute alcohol intoxication (AAI) is a life-threatening medical condition resulting from excessive alcohol consumption. Our research revealed the potential of morin (MOR) in treating AAI. However, MOR's effectiveness against AAI was hindered by its poor solubility in water and low bioavailability. In this study, our aim was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance MOR's solubility and bioavailability, evaluate its anti-AAI effects, and investigate the underlying mechanism. The composition of MOR-loaded self-nanoemulsifying drug delivery system (MOR-SNEDDS) was determined by constructing pseudo-ternary phase diagrams, and its formulation proportion was optimized using the Box-Behnken design. Following characterization of MOR-SNEDDS, we investigated its pharmacokinetics and biodistribution in healthy animals. Additionally, we assessed the anti-AAI effects and gastric mucosal protection of MOR-SNEDDS in an AAI mice model, exploring potential mechanisms. After breaking down into tiny droplets, the optimized mixture of MOR-SNEDDS showed small droplet size on average, even distribution, strong stability, and permeability. Pharmacokinetic studies indicated that MOR-SNEDDS, compared to a MOR suspension, increased the area under the plasma concentration-time curve (AUC0-t) by 10.43 times. Additionally, studies on how drugs move and are distributed in the body showed that MOR-SNEDDS had an advantage in passively targeting the liver. Moreover, in a mouse model for alcohol addiction, MOR not only decreased alcohol levels by boosting the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the stomach and liver, which counteracted the loss of righting reflex (LORR), but also reduced alcohol-induced damage to the stomach lining by lowering malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) levels. Furthermore, MOR-SNEDDS notably amplified these effects. MOR exhibits significant potential as a new medication for treating AAI, and utilizing MOR-SNEDDS with high oral bioavailability represents a promising new strategy in combating AAI.

QbD Approach for the Development of Tea Tree Oil-Enhanced Microemulgel Loaded with Curcumin and Diclofenac for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis, a chronic autoimmune disorder affecting millions worldwide each year, poses a significant threat due to its potential for progressive joint damage and debilitating pain if left untreated. Topical anti-inflammatory and analgesic treatments offer localized relief with reduced systemic side effects compared to conventional oral therapies, making them a promising option for managing rheumatoid arthritis. Therefore, the current study endeavored to formulate a microemulsion gel formulation loaded with diclofenac and curcumin for topical administration in the management of rheumatoid arthritis, utilizing Tea tree oil. The ratio of surfactant and cosurfactant was 4:1, assessed by pseudoternary phase diagram on the basis of the maximum emulsification region. The microemulsion underwent optimization using a Central Composite Rotatable Design (CCRD) with constraints of minimum particle size, polydispersity index, and maximum transmittance. The Curcufenac-T microemulsion had a particle size, polydispersity index (PDI), and transmittance of 151.82 ± 15.9 nm, 0.287 ± 0.021, and -5.78 ± 0.26 mV, respectively. DSC analyses confirmed the stability and compatibility of diclofenac and curcumin within the formulation. The microemulsion was changed into gel form by incorporating 1% carbopol-934. Skin permeation analysis revealed that the percentage of diclofenac permeated at 0.5 h from Curcufenac-T microemugel and the conventional gel was 12.1% and 3.9%, respectively, while at 12 h, the rates were 82.6% and 34.2%, respectively. In vitro permeability demonstrated significant potential for the effective delivery of diclofenac and curcumin to targeted sites, compared to conventional gel. Therefore, it was deduced that the Tea tree oil integrated diclofenac and curcumin microemulsion gel could enhance the effectiveness of diclofenac and serve as a promising vehicle for rheumatoid arthritis treatment.

Design and Evaluation of Microemulsion-Based Drug Delivery Systems for Biofilm-Based Infection in Burns

Normal skin is the first line of defense in the human body. A burn injury makes the skin susceptible to bacterial infection, thereby delaying wound healing and ultimately leading to sepsis. The chances of biofilm formation are high in burn wounds due to the presence of avascular necrotic tissue. The most common pathogen to cause burn infection and biofilm is Pseudomonas aeruginosa. The purpose of this study was to create a microemulsion (ME) formulation for topical application to treat bacterial burn infection. In the present study, tea tree oil was used as the oil phase, Tween 80 and transcutol were used as surfactants, and water served as the aqueous phase. Pseudo ternary phase diagrams were used to determine the design space. The ranges of components as suggested by the design were chosen, optimization of the microemulsion was performed, and in vitro drug release was assessed. Based on the characterization studies performed, it was found that the microemulsion were formulated properly, and the particle size obtained was within the desired microemulsion range of 10 to 300 nm. The I release study showed that the microemulsion followed an immediate release profile. The formulation was further tested based on its ability to inhibit biofilm formation and bacterial growth. The prepared microemulsion was capable of inhibiting biofilm formation.Graphical

Self-Microemulsifying Drug Delivery System to Enhance Oral Bioavailability of Berberine Hydrochloride in Rats.

Berberine hydrochloride (BH) is a versatile bioactive compound derived from the plants of the Berberis genus, known for its various pharmacological effects. However, its oral bioavailability is low due to its high hydrophilicity and limited permeability. To enhance its clinical efficacy and oral bioavailability, this study designed and prepared a BH-loaded self-microemulsifying drug delivery system (BH-SMEDDS), and characterized its in vitro and in vivo properties. Firstly, the optimal formulation of BH-SMEDDS was selected using solubility evaluations, pseudo-ternary phase diagrams, and particle size analysis. The formulation containing 55% Capmul MCM, 22.5% Kolliphor RH 40, and 22.5% 1,2-propanediol was developed. BH-SMEDDS exhibited stable physicochemical properties, with an average particle size of 47.2 ± 0.10 nm and a self-emulsification time of 26.02 ± 0.24 s. Moreover, in vitro dissolution studies showed significant improvements in BH release in simulated intestinal fluid, achieving 93.1 ± 2.3% release within 300 min. Meanwhile, BH-SMEDDS did not exhibit cytotoxic effects on the Caco-2 cells. Additionally, BH-SMEDDS achieved a 1.63-fold increase in oral bioavailability compared to commercial BH tablets. Therefore, SMEDDS presents a promising strategy for delivering BH with enhanced oral bioavailability, demonstrating significant potential for clinical application.

Developing Self-Nanoemulsifying Drug Delivery Systems Comprising an Artemether-Lumefantrine Fixed-Dose Combination to Treat Malaria.

Despite attempts to control malaria, poor drug bioavailability means malaria still places enormous pressure on health globally. It has been found that the solubility of highly lipophilic compounds can be enhanced through lipid formulations, e.g., self-emulsifying drug delivery systems (SEDDSs). Thus, quality-by-design and characterization were used to justify the development and determine the feasibility of oral oil-in-water SEDDSs comprising a fixed-dose combination (FDC) of artemether-lumefantrine to treat malaria more effectively without the aid of a fatty meal. These formulations were compared to a commercial product containing the same active compounds. Excipient compatibility and spontaneous emulsification capacity of different FDC-excipient combinations were identified by employing isothermal microcalorimetry, solubility, and water titration tests. Pseudoternary phase diagrams were constructed, and checkpoint formulations were selected within the self-emulsification region by reviewing formulation properties essential for optimized drug delivery. SEDDSs capable of enduring phase separation within 24 h were subjected to characterization experiments, i.e., drug concentration determination, cloud point, droplet size, size distribution, self-emulsification time, self-emulsification efficacy, viscosity, zeta potential, and thermodynamic stability analysis. SEDDSs with favorable characteristics were identified in the micro or nano range (SNEDDSs) before being subjected to drug release studies. All final formulations depicted enhanced artemether and lumefantrine release compared to the commercial product, which could not release lumefantrine at a quantifiable concentration in this study. The avocado oil (AVO)4:6 and olive oil (OLV)3:7 SNEDDSs overall portrayed the ideal characteristics and depicted the highest percentage of drug release. This study offers evidence that SNEDDSs from selected natural oils comprising an artemether-lumefantrine FDC can potentially enhance the bioavailability of these lipophilic drugs.

Microemulsions strongly promoted the activity of α-bisabolol against different Leishmania species and its skin permeation

This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.

Preparation of preservation paper containing essential oil microemulsion and its application in maintain the quality of post-harvest peaches

Post-harvest peaches are highly susceptible to fungal infections leading to spoilage. This study investigates the utilization of three edible plant essential oils (EOs) with antifungal properties for the preservation of peaches, along with an evaluation of their preservative efficacy. Initially, GC-MS was employed to identify the primary constituents of the EOs, revealing a predominance of phenols, alcohols, hydrocarbons and aldehydes. Principal component analysis was conducted to compare the chemical compositions of the EOs from the plants used in this study with those obtained from other regions. This analysis facilitates the quality assessment of the plant materials in the later stages of the research. In vitro antimicrobial assays indicated that the three EOs independently exhibited their respective antifungal activities against 7 fungi responsible for peach spoilage. The Response Surface Methodology was then applied to optimize the blend ratio of the composite EOs (CEOs) for maximum antifungal efficacy. Concurrently, this study validated the rationality of a second-order polynomial model that correlates the peach decay index with the concentration of the CEOs. To enhance the bioavailability of the CEOs, a pseudo-ternary phase diagram was employed to formulate the CEOs into a microemulsion. Based on the RSM optimization results for the CEOs, the optimal mass ratio of the components within the microemulsion was determined. Using this microemulsion as a base, preservative films were developed that demonstrated a significant preservation effect on peaches, highlighting the immense potential of this research in the food industry.

Topical Delivery of Voriconazole Loaded on Lyotropic Liquid Crystal Gel for Management of Fungal Infections

Topical antifungal therapy is recommended for the treatment of fungal infections of the skin. Due to its benefits, including the ability to direct drugs to the infection site and a lower chance of systemic adverse effects. The nano size and structure of LLC with the skin enhance the permeation and deposition of drugs within deep parts of skin. In this a novel formulation of voriconazole LLC gel was planned. Surfactant, co-surfactant, oil, and water pseudo-ternary phase diagrams were created in order to determine the LLC gel and microemulsion zones. The formulations were evaluated using polarizing microscopy, FT-IR spectroscopy. For each formulation, the polydispersity index, zeta potential, and mean droplet size were determined. The release patterns revealed that the prepared LLC gel provide sustained release profile up to 24 hr. Ex-vivo permeation of selected formulations exhibited higher permeability values for voriconazole. The drug skin deposition results from selected formulations showed that, in comparison to other studied formulations, a much larger amount of the drug was deposited in the skin after 24 hours. The confocal pictures appeared that the LLC gel was able to provide fluorescent color to all skin layers. The skin irritation study data of LLC gel formulations could be announced as safe and non- irritant for human skin. The selected formulations underwent a six-month stability testing at room temperature and 4–8 °C. The results showed that the pH, drug content, and viscosity values did not change significantly during this time. Keywords: Lyotropic liquid crystal, Release and diffusion, Skin permeability, Skin deposition, Pathohistology

Redox-switchable microemulsions with efficient phase separation and surfactant recycling

HypothesisSwitchable microemulsions (MEs) are those capable of adaptively responding to the action of internal or external stimuli. For redox-switchable MEs to obtain high-efficiency phase separation and surfactant recycling, it may be one of the keys to adequately turn off the interfacial activity of surfactants and reduce the solubility of the closed surfactants in the oil phase. ExperimentsMonophasic MEs consisting 11-butylselanyl-undecyl sulfate sodium (C4SeC11SO4Na), n-butanol, n-octane, and water were fabricated using the pseudo-ternary phase diagram method. Their structural features and droplets size were characterized by conductivity, dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM), respectively. The redox response of MEs was studied using a combination of visual observations and DLS, cryo-TEM, nuclear magnetic resonance (NMR) and thin-layer tomography. The efficient recycling of C4SeC11SO4Na from a well-emulsified eluent is conceptually demonstrated. FindingsThe reversible transition between C4SeC11SO4Na and C4SeOC11SO4Na is achieved under the alternating action of H2O2 and N2H4, by which C4SeC11SO4Na-based monophasic MEs are able to efficiently demulsify and regenerate, respectively, regardless of their type. After H2O2-induced demulsification of the MEs, C4SeOC11SO4Na can be efficiently recycled with the water phase. We hope that such a redox-switching method may benefit some technological applications. For example, it offers exciting possibilities for simultaneous recycling C4SeC11SO4Na and removal of oil from a well-emulsified eluent. Around 97.1 ± 0.3 % of C4SeC11SO4Na could be recycled over five cycles with no apparent loss. After a simple and conventional treatment with anion-exchange resin and active carbon, the total organic carbon and chemical oxygen demand of the waste water were 17.4 ± 2.8 and 26.2 ± 1.4 mg/L, respectively.

Pseudoternary Phase Diagram and Antibacterial Activity of Microemulsion-Based Citronella Oil

Citronella oil (CTO) is extracted from citronella leaves by maceration or steam distillation process, which has antibacterial and insect-repellent activities. However, the use of CTO is limited and requires modification in other formulations, such as microemulsion (ME), to increase its bioactivities. ME consists of oil, water, surfactant and/or cosurfactant and is commonly applied in food and beverages, cosmetics, and carrier for drug delivery applications. CTO was used as the oil phase for ME with nonionic surfactant and ethanol as a cosurfactant for lowering interfacial tension between oil and water phase. Subsequent observations regarding stability and antibacterial tests were carried out on ME formulations with surfactant/cosurfactant mixture of 2 due to its largest ME area. A hydrodynamic diameter analysis was also carried out to see the stability of the ME within a period of 50 d. ME with 10% CTO, 30% surfactant mixture, and 60% water showed the best formulation observed from the consistent hydrodynamic diameter measurement. In addition, ME with different formulations could inhibit the growth of Escherichia coli and Staphylococcus aureus by more than 90%. From this research, CTO-based ME potentially improve and develop drug carrier applications, especially via topical route.

Development and Characterization of a Microemulsion Containing a Cannabidiol Oil and a Hydrophilic Extract from Sambucus ebulus for Topical Administration.

Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic anti-inflamatory and antioxidant activities. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with potential anti-inflammatory and antioxidant activity for the topical treatment of inflammatory skin disorders. The microemulsion system was composed of a 20% CBD oil, which served as the hydrophobic phase; Labrasol/Plurol Oleique (1:1), which served as surfactant and cosurfactant (S/CoS), respectively; and an aqueous vegetal extract obtained from Sambucus ebulus L. (S. ebulus) ripe fruits, which has potential anti-oxidant and anti-inflammatory activity and which served as the aqueous phase. A pseudo-ternary phase diagram was generated, leading to the selection of an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after its reproducibility was tested, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size (by laser scattering), compatibility of components (by differential scanning calorimetry) and rheological properties (using a rotational rheometer). The designed microemulsion showed good stability and slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the aqueous phase of the microemulsion were studied via in vitro diffusion experiments using flow-through diffusion cells and were compared to those of a CBD oil and a microemulsion containing only CBD as an active substance. It was found that the inclusion of the original oil in microemulsions did not result in a significant modification of the release of CBD, suggesting the possibility of including hydrophilic active compounds in the formulation and establishing an interesting strategy for the development of future formulations.

Fabrication and characterization of transdermal delivery of ribociclib nanoemulgel in breast cancer treatment

The objective of this study is to create a nanoemulgel formulation of Ribociclib (RIBO), a highly selective inhibitor of CDK4/6 through the utilization of spontaneous emulsification method. An experimental investigation was conducted to construct pseudo-ternary phase diagram for the most favourable formulation utilizing rice bran oil, which is known for its diverse anticancer properties. The formulation consisted of varying combination of the surfactant and as the co-surfactant (Tween 80 and Transcutol, respectively) referred to as Smix and the trials were optimized to get the desired outcome. The nanoemulsion (NE) formulations that were developed exhibited a droplet size of 179.39 nm, accompanied with a PDI of 0.211. According to the data released by Opt-RIBO-NE, it can be inferred that the Higuchi model had the most favourable fit among many kinetics models considered. The results indicate that the use of nanogel preparations for the topical delivery of RIBO in breast cancer therapy, specifically RIBO-NE-G, is viable. This is supported by the extended release of the RIBO, and the appropriate level of drug permeation observed in Opt-RIBO-NE-G. Due to RIBO and Rice Bran oil, RIBO-NE-G had greater antioxidant activity, indicating its effectiveness as antioxidants. The stability of the RIBO-NE-G was observed over a period of three months, indicating a favourable shelf life. Therefore, this study proposes the utilization of an optimized formulation of RIBO-NE-G may enhance the efficacy of anticancer treatment and mitigate the occurrence of systemic side effects in breast cancer patients, as compared to the use of suspension preparation of RIBO.