Norazlinaliza Salim

Phase Behaviour, Formation and Characterization of Palm-Based Esters Nanoemulsion Formulation containing Ibuprofen

Palm-based esters, synthesized through enzymatic transesterification of palm oil fractions with oleyl alcohol have potential application in pharmaceutical formulations. The phase behaviour of palm-based esters containing ibuprofen with surfactant of different HLB values was investigated for topical delivery system. The surfactants were Tween 85, Tween 60 and Tween 80, and the palm-based esters were palm oil esters (POEs) and palm kernel oil esters (PKOEs). Ternary phase diagrams of palm-based esters: Ibuprofen/surfactant/water systems were constructed. Three distinct regions were observed in the phase diagrams; isotropic liquid region, L 1 , liquid crystalline region, L c and multiphase region, M. Nanoemulsions were prepared spontaneously by the addition of water to oil:ibuprofen/surfactant mixtures based on the ternary phase diagrams constructed. Formulations from the PKOEs:Ibuprofen/Tween 80/water systems were selected due to the presence of large isotropic liquid region, which suggested that this region was suitable to be used in producing nanoemulsions. Particle size analysis showed that the mean particle sizes of these formulations ranged from 10 nm to 70 nm. Zeta potential analysis for all formulations showed negative values from -4 to -8 mV. Stability studies showed that, after 4 h of stirring at room temperature (25°C), the formulations were stable under centrifugation test at 4000 rpm for 15 min. Stability under different storage temperature showed that at 25°C, the four formulations, F1, F2, F3 and F4 were stable with no phase separation for the duration of 1 month. However, when these formulations were stored at 45°C and 4°C, respectively, only F3 and F4 were observed to be stable. These two formulations have the potential to be used for topical delivery of ibuprofen.

Modification of palm kernel oil esters nanoemulsions with hydrocolloid gum for enhanced topical delivery of ibuprofen

Introduction During recent years, there has been growing interest in the use of nanoemulsion as a drug-carrier system for topical delivery. A nanoemulsion is a transparent mixture of oil, surfactant and water with a very low viscosity, usually the product of its high water content. The present study investigated the modification of nanoemulsions with different hydrocolloid gums, to enhanced drug delivery of ibuprofen. The in vitro characterization of the initial and modified nanoemulsions was also studied. Methods A palm kernel oil esters nanoemulsion was modified with different hydrocolloid gums for the topical delivery of ibuprofen. Three different hydrocolloids (gellan gum, xanthan gum, and carrageenan) were selected for use. Ternary phase diagrams were constructed using palm kernel oil esters as the oil, Tween 80 as the surfactant, and water. Nanoemulsions were prepared by phase inversion composition, and were gradually mixed with the freshly prepared hydrocolloids. The initial nanoemulsion and modified nanoemulsions were characterized. The abilities of the nanoemulsions to deliver ibuprofen were assessed in vitro, using a Franz diffusion cell fitted with rat skin. Results No significant changes were observed in droplet size (~16–20 nm) but a significant difference in polydispersity indexes were observed before and after the modification of nanoemulsions using gellan gum, carrageenan, and xanthan gum. The zeta potentials of the initial nanoemulsions (−11.0 mV) increased to −19.6 mV, −13.9 mV, and −41.9 mV, respectively. The abilities of both the initial nanoemulsion (T802) and the modified nanoemulsion to deliver ibuprofen through the skin were evaluated in vitro, using Franz diffusion cells fitted with rat skin. The in vitro permeation data showed that the modified nanoemulsion (Kp value of 55.4 × 10−3 cm · h−1) increased the permeability of ibuprofen 4.40 times over T802 (Kp value of 12.6 × 10−3 cm · h−1) (P < 0.05). Conclusion The modified nanoemulsion may be a promising vehicle to enhance the permeation of ibuprofen for topical delivery.

Nanoemulsion as a topical delivery system of antipsoriatic drugs

Psoriasis is one of the most common skin diseases, affecting 2–5% of the worlds population. It is a skin autoimmune disorder, resulting in an excessive growth and aberrant differentiation of keratinocytes. Psoriasis is an incurable lifetime disease which can only be controlled and relieved through medication. Various approaches have been explored to treat the disease. Treatment of psoriasis includes topical therapy, systemic therapy and phototherapy. Topical therapy is the first line treatment and it is the most practical medication method for psoriasis patients. However, the conventional topical treatments such as gel and cream have low efficiency, poor cosmetic and aesthetic appeal, leading to poor patient compliance or adherence, while systemic and photo therapy produce significant adverse side effects. Nanoemulsion is defined as an emulsion system consisting of oil, surfactant, and water with an isotropic, transparent (or translucent) appearance. The emulsion droplet size is defined to be less than 200 nm. Nonetheless, if the emulsion has low surfactant content and is kinetically stable, a size of less than 500 nm can be accepted as nanoemulsion. A small droplet size would enhance the delivery and penetration of a drug through the psoriasis skin layer. There has been a growing interest in using nanoemulsions in topical applications, due to their high stability and their optical transparency or translucency, which make them good and very dermatologically attractive. A good selection of oils and surfactants would enhance the transdermal treatment efficacy. This review highlights the potential of drug-loaded nanoemulsions for the treatment of psoriasis towards achieving better efficacy and eliminating side effects.

Enhancement of physicochemical properties of nanocolloidal carrier loaded with cyclosporine for topical treatment of psoriasis: in vitro diffusion and in vivo hydrating action

Psoriasis is a chronic autoimmune disease that cannot be cured. It can however be controlled by various forms of treatment, including topical, systemic agents, and phototherapy. Topical treatment is the first-line treatment and favored by most physicians, as this form of therapy has more patient compliance. Introducing a nanoemulsion for transporting cyclosporine as an anti-inflammatory drug to an itchy site of skin disease would enhance the effectiveness of topical treatment for psoriasis. The addition of nutmeg and virgin coconut-oil mixture, with their unique properties, could improve cyclosporine loading and solubility. A high-shear homogenizer was used in formulating a cyclosporine-loaded nanoemulsion. A D-optimal mixture experimental design was used in the optimization of nanoemulsion compositions, in order to understand the relationships behind the effect of independent variables (oil, surfactant, xanthan gum, and water content) on physicochemical response (particle size and polydispersity index) and rheological response (viscosity and k-value). Investigation of these variables suggests two optimized formulations with specific oil (15% and 20%), surfactant (15%), xanthan gum (0.75%), and water content (67.55% and 62.55%), which possessed intended responses and good stability against separation over 3 months’ storage at different temperatures. Optimized nanoemulsions of pH 4.5 were further studied with all types of stability analysis: physical stability, coalescence-rate analysis, Ostwald ripening, and freeze–thaw cycles. In vitro release proved the efficacy of nanosize emulsions in carrying cyclosporine across rat skin and a synthetic membrane that best fit the Korsmeyer–Peppas kinetic model. In vivo skin analysis towards healthy volunteers showed a significant improvement in the stratum corneum in skin hydration.

Improvement of physicochemical properties of nanocolloidal carrier loaded with low water solubility drug for parenteral cancer treatment by Response Surface Methodology

Nanoemulsions have been used as a drug carrier system, particularly for poorly water-soluble drugs. Sorafenib is a poorly soluble drug and also there is no parenteral treatment. The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib. The formulations were prepared by high energy emulsification method and optimized by using Response Surface Methodology (RSM). Here, the effect of independent composition variables of lecithin (1.16-2.84%, w/w), Medium-Chain Triglycerides (2.32-5.68%, w/w) and polysorbate 80 (0.58-1.42%, w/w) amounts on the properties of Sorafenib-loaded nanoemulsion was investigated. The three responses variables were particle size, zeta potential, and polydispersity index. Optimization of the conditions according to the three dependent variables was performed for the preparation of the Sorafenib-loaded nanoemulsions with the minimum value of particle size, suitable rage of zeta potential, and polydispersity index. A formulation containing 0.05% of Sorafenib kept its properties in a satisfactory range over the evaluated period. The composition with 3% Medium-Chain Triglycerides, 2.5% lecithin and 1.22% polysorbate 80 exhibited the smallest particle size and polydispersity index (43.17 nm and 0.22, respectively) with the zeta potential of -38.8 mV was the optimized composition. The fabricated nanoemulsion was characterized by the transmission electron microscope (TEM), viscosity, and stability assessment study. Also, the cytotoxicity result showed that the optimum formulations had no significant effect on a normal cell in a low concentration of the drug but could eliminate the cancer cells. The dose-dependent toxicity made it a suitable candidate for parenteral applications in the treatment of breast cancer. Furthermore, the optimized formulation indicated good storage stability for 3 months at different temperatures (4 ± 2 °C, 25 ± 2 °C and 45 ± 2 °C).

Palm-based nanoemulsions for drug delivery systems

Abstract Palm-based nanoemulsion has played a significant role as a biocompatible delivery system in various industries, but has yet to achieve its full potential since little information about formulation with palm oil is known. Such a nanoemulsion can be developed and optimized systematically to attain excellent physicochemical properties, such as low viscosity, high kinetic stability, and large interfacial area, while being safe for human use. Most poorly water-soluble drugs could be loaded in this nanoemulsion and delivered efficiently to the target sites. This chapter summarizes recent studies conducted on the development of palm-based nanoemulsion, physicochemical characterization in contributing to drug efficacy, and in vitro permeation studies. Computational simulation study was used as a tool to investigate the self-assembly process and physicochemical properties at atomic details, based on experimentally phase diagrams obtained. Deeper understanding and research on nanodelivery via palm-based nanoemulsion will give positive impact, especially on the pharmaceutical industries.

Optimization of Quercetin loaded Palm Oil Ester Based Nanoemulsion Formulation for Pulmonary Delivery

In this research, the palm oil ester (POE)- based nanoemulsion formulation containing quercetin for pulmonary delivery was developed. The nanoemulsion formulation was prepared by high energy emulsification method and then further optimized using D-optimal mixture design. The concentration effects of the mixture of POE:ricinoleic acid (RC), ratio 1:1 (1.50-4.50 wt.%), lecithin (1.50-2.50 wt.%), Tween 80 (0.50-1.00 wt.%), glycerol (1.50-3.00 wt.%), and water (88.0-94.9 wt.%) towards the droplet size were investigated. The results showed that the optimum formulation with 1.50 wt.% POE:RC, 1.50 wt.% lecithin, 1.50 wt.% Tween 80, 1.50 wt.% glycerol and 93.90 % water was obtained. The droplet size, polydispersity index (PDI) and zeta potential of the optimized formulation were 110.3 nm, 0.290 and －37.7 mV, respectively. The formulation also exhibited good stability against storage at 4℃ for 90 days. In vitro aerosols delivery evaluation showed that the aerosols output, aerosols rate and median mass aerodynamic diameter of the optimized nanoemulsion were 99.31%, 0.19 g/min and 4.25 µm, respectively. The characterization of physical properties and efficiency for aerosols delivery results suggest that POE- based nanoemulsion containing quercetin has the potential to be used for pulmonary delivery specifically for lung cancer treatment.