Propylene Glycol Caprylate-Based Nanoemulsion Formulation of Plumbagin: Development and Characterization of Anticancer Activity

Plumbagin, a bioactive naphthoquinone, has demonstrated potent antitumor potential. However, plumbagin is a sparingly water-soluble compound; therefore, clinical translation requires and will be facilitated by the development of a new pharmaceutical formulation. We have generated an oil-in-water nanoemulsion formulation of plumbagin using a low-energy spontaneous emulsification process with propylene glycol caprylate (Capryol 90) as an oil phase and Labrasol/Kolliphor RH40 as surfactant and cosurfactant excipients. Formulation studies using Capryol 90/Labrasol/Kolliphor RH40 components, based on pseudoternary diagram and analysis of particle size distribution and polydispersity determined by dynamic light scattering (DLS), identified an optimized composition of excipients for nanoparticle formulation. The nanoemulsion loaded with plumbagin as an active pharmaceutical ingredient had an average hydrodynamic diameter of 30.9 nm with narrow polydispersity. The nanoemulsion exhibited long-term stability, as well as good retention of particle size in simulated physiological environments. Furthermore, plumbagin-loaded nanoemulsion showed an augmented cytotoxicity against prostate cancer cells PTEN-P2 in comparison to free drug. In conclusion, we generated a formulation of plumbagin with high loading drug capacity, robust stability, and scalable production. Novel Capryol 90-based nanoemulsion formulation of plumbagin demonstrated antiproliferative activity against prostate cancer cells, warranting thus further pharmaceutical development.

Diallyl Trisulfide, the Antifungal Component of Garlic Essential Oil and the Bioactivity of Its Nanoemulsions Formed by Spontaneous Emulsification

The aim of this study was to evaluate the chemical compounds of garlic essential oil (EO), and determine the antifungal efficacy of garlic EO and its major components, diallyl trisulfide and its nanoemulsions against wood-rotting fungi, Trametes hirsuta and Laetiporus sulphureus. GC-MS analysis revealed that the major constituents of garlic EO were diallyl trisulfide (39.79%), diallyl disulfide (32.91%), and diallyl sulfide (7.02%). In antifungal activity, the IC50 value of garlic EO against T. hirsuta and L. sulphureus were 137.3 and 44.6 μg/mL, respectively. Results from the antifungal tests demonstrated that the three major constituents were shown to have good antifungal activity, in which, diallyl trisulfide was the most effective against T. hirsuta and L. sulphureus, with the IC50 values of 56.1 and 31.6 μg/mL, respectively. The diallyl trisulfide nanoemulsions showed high antifungal efficacy against the examined wood-rotting fungi, and as the amount of diallyl trisulfide in the lipid phase increases, the antifungal efficacy of the nanoemulsions increases. These results showed that the nanoemulsions and normal emulsion of diallyl trisulfide have potential to develop into a natural wood preservative.

Artificial Inclusion Environments—Replicating Industry in the Laboratory

The authors present a series of complementary test methods which were developed and used to investigate reactions between high aluminium steel and silica rich inclusions. Non-metallic inclusions (NMIs) cause many defects in the final steel product, therefore the ability to track their size, morphology and composition and correlate this with fundamental reaction kinetics provides important knowledge to support the production of clean quality steel products. Novel steel grades such as TRIP, TWIP and low-density steels have high aluminium contents; aluminium is a readily oxidisable species presenting the potential for instability and excessive reaction with commonly used mould powders that contain silica. A novel combination of techniques including HT-CLSM (High-Temperature Confocal Laser Scanning Microscope), XCT (X-ray computed tomography) and SEM/EDS (scanning electron microscopy/electron dispersive spectroscopy) have been used to study the interaction of entrained mould powder inclusions with steel at high temperatures simulating industrial conditions. This report presents a discussion on the development of techniques and samples to achieve representative and repeatable results that can provide information on the complex chemical and physical interaction phenomena with confidence. Each experimental technique had its own learning points and consequent results. Outcomes presented include possible confirmation of the chemical reaction rate controlling step being aluminium mass transfer; heterogeneous local environmental conditions including fluidity and chemical composition; and occurrence of spontaneous emulsification where the mould powder inclusion breaks apart into a cloud of smaller fragments.

FORMULATION AND EVALUATION OF TOPICAL NANOEMULGEL OF METHOTREXATE FOR RHEUMATOID ARTHRITIS

Objective: The purpose of this study was to develop and evaluate methotrexate-loaded nanoemulgel for topical delivery in the management of rheumatoid arthritis. Methods: Based on nanoemulsion composition, the pseudo ternary phase diagram was fabricated by using peanut oil, Tween 20 as the surfactant, and PEG 400 being used as a co-surfactant. The methotrexate-loaded nanoemulsion was formulated by using the spontaneous emulsification method. Badam gum was used as a gel matrix in the prepared nanoemulsion to form nanoemulgel. The methotrexate loaded nanoemulgel was characterized and evaluated for pH, particle size, physical appearance, viscosity, spreadability, TEM, drug content, diffusion study, release kinetics, and stability studies. Results: The nanoemulgel constituting 8.6% peanut oil, 34.4% of Tween 20 and PEG 400 as Smix (surfactant and co-surfactant mixture), 43% water, and 12.5% w/w badam gum was concluded as optimized formulation. The prepared nanoemulgel was translucent in nature having a particle size of 195.1nm and zeta potential of -0.278mV. Drug content and drug release for the optimized formulation were found to be 98.11±0.34% and 95.11±0.02% respectively. pH, viscosity, and spreadability were found to be optimum. Stability study data showed that the prepared nanoemulgel was stable at different temperatures varying from -25 to +45ºC. Conclusion: Methotrexate loaded nanoemulgel has been formulated for topical drug delivery for the management of rheumatoid arthritis.

Development and Evaluation of Nanoemulsions for Phenytoin Drug Loading

Aims: To understand about the nanoemulsion types and the process formation of spontaneous emulsification method by phase inversion. Then to test the different combinations of Oil, Surfactants and Co-surfactants for formation of suitable nanoemulsions for phenytoin drug loading. Study Design: Spontaneous emulsification method by phase inversion used to form the nanoemulsions. Place and Duration of Study: Department of Pharmaceutical Sciences, Kumaun University, Nainital, Uttarakhand, India. Methodology: Phenytoin is a widely used drug in anticonvulsants class for epilepsy which comes under BCS Class II of drug category. Phenytoin has high permeability property but it also shows low solubility property which makes it difficult to absorb from GI tract hence make a poor penetration into the brain to target disease in the CNS. To overcome the situation of poor delivery of phenytoin, the requirement of nanoparticulate drug delivery as an innovative and effective drug delivery system from nose to brain raised. The objective of our study was to find the best combination of oil and Smix (surfactant and co-surfactant mixture) to form o/w (Oil in Water) nanoemulsions suitable for loading phenytoin drug using spontaneous emulsification method for brain targeting. Results: Based on different compositions of oil (sunflower), surfactants (Tween-20), and co-surfactants (Transcutol P), forty-five test mixtures were made, water titration technique was employed for preparing the pseudo-ternary-phase diagrams. On the basis of these phase diagrams twenty-five phenytoin loaded nanoemulsions were formulated and further examined. After physicochemical characterization of these formulations the viscosity, pH, RI and % transmittance was found (6.149 ± 0.084 to 9.114 ± 0.027), (6.546 ± 0.018 to 6.656 ± 0.017), (1.395 ± 0.003 to 1.41 ± 0.005) and (94.53 ± 1.4% to 95.58 ± 1.2%) respectively. The release rate of phenytoin was found very satisfactory i.e., 98.51 ± 0.25 % to 99.82 ± 0.28 % after 24 hrs. The four formulations showed best release rate had further taken for particle size analysis. The particle size analysis showed that all the properties were in the desired range i.e., droplet size (18.9 to 21.9), zeta potential (-12.4 to -28.8), PDI (0.334 to 0.363). The study shows that the phenytoin loaded nanoemulsion is possible to make by water titration method and shall have a good drug release rate. Conclusion: The nanoemulsion formulations passed through stress testing had also showed good release rate of phenytoin. Also, the other parameters like viscosity, pH, RI and percentage transmittance were in a quit satisfactory range to proceed further with these formulations. The particle size analysis confirms the formation of nanoemultions which had very good drug release rates.

Water-in-Oil Nano-Emulsions Prepared by Spontaneous Emulsification: New Insights on the Formulation Process

Nano-emulsions consist of stable suspensions of nano-scaled droplets that have huge loading capacities and are formulated with safe compounds. For these reasons, a large number of studies have described the potential uses of nano-emulsions, focusing on various aspects such as formulation processes, loading capabilities, and surface modifications. These studies typically concern direct nano-emulsions (i.e., oil-in-water), whereas studies on reverse nano-emulsions (i.e., water-in-oil) remain anecdotal. However, reverse nano-emulsion technology is very promising (e.g., as an alternative to liposome technology) for the development of drug delivery systems that encapsulate hydrophilic compounds within double droplets. The spontaneous emulsification process has the added advantages of optimization of the energetic yield, potential for industrial scale-up, improved loading capabilities, and preservation of fragile compounds targeted for encapsulation. In this study, we propose a detailed investigation of the processes and formulation parameters involved in the spontaneous nano-emulsification that produces water-in-oil nano-emulsions. The following details were addressed: (i) the order of mixing of the different compounds (method A and method B), (ii) mixing rates, (iii) amount of surfactants, (iv) type and mixture of surfactants, (v) amount of dispersed phase, and (vi) influence of the nature of the oil. The results emphasized the effects of the formulation parameters (e.g., the volume fraction of the dispersed phase, nature or concentration of surfactant, or nature of the oil) on the nature and properties of the nano-emulsions formed.