Anti-inflammatory and analgesic effects of ketoprofen in palm oil esters nanoemulsion

Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of ketoprofen produces serious gastrointestinal adverse effects. One of the promising methods to overcome these adverse effects is to administer the drug through the skin. The aim of the present work is to evaluate the anti-inflammatory and analgesic effects from topically applied ketoprofen entrapped palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen product, Fastum® gel. The novelty of this study is, use of POEs for the oil phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based nanoemulsion formulation and market formulation. Results indicated that there are no significant different between ketoprofen entrapped POEs nanoemulsion and market formulation in carrageenan-induced rat hind paw edema study and carrageenan-induced hyperalgesia pain threshold study. However, it shows a significant different between POEs nanoemulsion formulation and control group in these studies at p<0.05. From these results it was concluded that the developed nanoemulsion have great potential for topical application of ketoprofen

Effect of surfactant and surfactant blends on pseudoternary phase diagram behavior of newly synthesized palm kernel oil esters

Background: The purpose of this study was to select appropriate surfactants or blends of surfactants to study the ternary phase diagram behavior of newly introduced palm kernel oil esters. Methods: Nonionic surfactant blends of Tween® and Tween®/Span® series were screened based on their solubilization capacity with water for palm kernel oil esters. Tween® 80 and five blends of Tween® 80/Span® 80 and Tween® 80/Span® 85 in the hydrophilic-lipophilic balance (HLB) value range of 10.7–14.0 were selected to study the phase diagram behavior of palm kernel oil esters using the water titration method at room temperature. Results: High solubilization capacity was obtained by Tween® 80 compared with other surfactants of Tween® series. High HLB blends of Tween® 80/Span® 85 and Tween® 80/Span® 80 at HLB 13.7 and 13.9, respectively, have better solubilization capacity compared with the lower HLB values of Tween® 80/Span® 80. All the selected blends of surfactants were formed as waterin- oil microemulsions, and other dispersion systems varied in size and geometrical layout in the triangles. The high solubilization capacity and larger areas of the water-in-oil microemulsion systems were due to the structural similarity between the lipophilic tail of Tween® 80 and the oleyl group of the palm kernel oil esters. Conclusion: This study suggests that the phase diagram behavior of palm kernel oil esters, water, and nonionic surfactants is not only affected by the HLB value, but also by the structural similarity between palm kernel oil esters and the surfactant used. The information gathered in this study is useful for researchers and manufacturers interested in using palm kernel oil esters in pharmaceutical and cosmetic preparation. The use of palm kernel oil esters can improve drug delivery and reduce the cost of cosmetics

Formulation and in vitro release evaluation of newly synthesized palm kernel oil esters-based nanoemulsion delivery system for 30% ethanolic dried extract derived from local Phyllanthus urinaria for skin antiaging

Elrashid Saleh Mahdi1, Azmin Mohd Noor1, Mohamed Hameem Sakeena1, Ghassan Z Abdullah1, Muthanna F Abdulkarim1, Munavvar Abdul Sattar2 1Department of Pharmaceutical Technology, 2Department of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia Background: Recently there has been a remarkable surge of interest about natural products and their applications in the cosmetic industry. Topical delivery of antioxidants from natural sources is one of the approaches used to reverse signs of skin aging. The aim of this research was to develop a nanoemulsion cream for topical delivery of 30% ethanolic extract derived from local Phyllanthus urinaria (P. urinaria) for skin antiaging. Methods: Palm kernel oil esters (PKOEs)-based nanoemulsions were loaded with P. urinaria extract using a spontaneous method and characterized with respect to particle size, zeta potential, and rheological properties. The release profile of the extract was evaluated using in vitro Franz diffusion cells from an artificial membrane and the antioxidant activity of the extract released was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method. Results: Formulation F12 consisted of wt/wt, 0.05% P. urinaria extract, 1% cetyl alcohol, 0.5% glyceryl monostearate, 12% PKOEs, and 27% Tween&amp;reg; 80/Span&amp;reg; 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and a 59.5% phosphate buffer system at pH 7.4. Formulation F36 was comprised of 0.05% P. urinaria extract, 1% cetyl alcohol, 1% glyceryl monostearate, 14% PKOEs, 28% Tween&amp;reg; 80/Span&amp;reg; 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and 56% phosphate buffer system at pH 7.4 with shear thinning and thixotropy. The droplet size of F12 and F36 was 30.74 nm and 35.71 nm, respectively, and their nanosizes were confirmed by transmission electron microscopy images. Thereafter, 51.30% and 51.02% of the loaded extract was released from F12 and F36 through an artificial cellulose membrane, scavenging 29.89% and 30.05% of DPPH radical activity, respectively. Conclusion: The P. urinaria extract was successfully incorporated into a PKOEs-based nanoemulsion delivery system. In vitro release of the extract from the formulations showed DPPH radical scavenging activity. These formulations can neutralize reactive oxygen species and counteract oxidative injury induced by ultraviolet radiation and thereby ameliorate skin aging. Keywords: nanoemulsions, Phyllanthus urinaria, skin antiaging, palm kernel oil ester

Effect of surfactant and surfactant blends on pseudoternary phase diagram behavior of newly synthesized palm kernel oil esters

Elrashid Saleh Mahdi1, Mohamed HF Sakeena1, Muthanna F Abdulkarim1, Ghassan Z Abdullah1,3, Munavvar Abdul Sattar2, Azmin Mohd Noor11Department of Pharmaceutical Technology, 2Department of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia; 3Department of Pharmaceutical Technology, International Medical University, Bukit Jalil, Kuala Lumpur, MalaysiaBackground: The purpose of this study was to select appropriate surfactants or blends of surfactants to study the ternary phase diagram behavior of newly introduced palm kernel oil esters.Methods: Nonionic surfactant blends of Tween&amp;reg; and Tween&amp;reg;/Span&amp;reg; series were screened based on their solubilization capacity with water for palm kernel oil esters. Tween&amp;reg; 80 and five blends of Tween&amp;reg; 80/Span&amp;reg; 80 and Tween&amp;reg; 80/Span&amp;reg; 85 in the hydrophilic-lipophilic balance (HLB) value range of 10.7&amp;ndash;14.0 were selected to study the phase diagram behavior of palm kernel oil esters using the water titration method at room temperature.Results: High solubilization capacity was obtained by Tween&amp;reg; 80 compared with other surfactants of Tween&amp;reg; series. High HLB blends of Tween&amp;reg; 80/Span&amp;reg; 85 and Tween&amp;reg; 80/Span&amp;reg; 80 at HLB 13.7 and 13.9, respectively, have better solubilization capacity compared with the lower HLB values of Tween&amp;reg; 80/Span&amp;reg; 80. All the selected blends of surfactants were formed as water-in-oil microemulsions, and other dispersion systems varied in size and geometrical layout in the triangles. The high solubilization capacity and larger areas of the water-in-oil microemulsion systems were due to the structural similarity between the lipophilic tail of Tween&amp;reg; 80 and the oleyl group of the palm kernel oil esters.Conclusion: This study suggests that the phase diagram behavior of palm kernel oil esters, water, and nonionic surfactants is not only affected by the HLB value, but also by the structural similarity between palm kernel oil esters and the surfactant used. The information gathered in this study is useful for researchers and manufacturers interested in using palm kernel oil esters in pharmaceutical and cosmetic preparation. The use of palm kernel oil esters can improve drug delivery and reduce the cost of cosmetics.Keywords: phase diagram, palm kernel oil esters, nonionic surfactants, microemulsion

Carbopol 934, 940 and Ultrez 10 as viscosity modifiers of palm olein esters based nano-scaled emulsion containing ibuprofen

Micro-emulsions and sometimes nano-emulsions are well known candidates to deliver drugs locally. However, the poor rheological properties are marginally affecting their acceptance pharmaceutically. This work aimed to modify the poor flow properties of a nano-scaled emulsion comprising palm olein esters as the oil phase and ibuprofen as the active ingredient for topical delivery. Three Carbopol ® resins: 934, 940 and Ultrez 10, were utilized in various concentrations to achieve these goals. Moreover, phosphate buffer and triethanolamine solutions pH 7.4 were used as neutralizing agents to assess their effects on the gel-forming and swelling properties of Carbopol ® 940. The addition of these polymers caused the produced nano-scaled emulsion to show a dramatic droplets enlargement of the dispersed globules, increased intrinsic viscosity, consistent zeta potential and transparent-to-opaque change in appearance. These changes were relatively influenced by the type and the concentration of the resin used. Carbopol ® 940 and triethanolamine appeared to be superior in achieving the proposed tasks compared to other materials. The higher the pH of triethanolamine solution, the stronger the flow-modifying properties of Carbopol ® 940. Transmission electron microscopy confirmed the formation of a well-arranged gel network of Carbopol ® 940, which was the major cause for all realized changes. Later in vitro permeation studies showed a significant decrease in the drug penetration, thus further modification using 10% w/w menthol or limonene as permeation promoters was performed. This resulted in in vitro and in vivo pharmacodynamics properties that are comparably higher than the reference chosen for this study

Apocynin and catalase prevent hypertension and kidney injury in Cyclosporine A-induced nephrotoxicity in rats.

Oxidative stress is involved in the pathogenesis of a number of diseases including hypertension and renal failure. There is enhanced expression of nicotinamide adenine dinucleotide (NADPH oxidase) and therefore production of hydrogen peroxide (H2O2) during renal disease progression. This study investigated the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on Cyclosporine A (CsA) nephrotoxicity in Wistar-Kyoto rats. Rats received CsA (25mg/kg/day via gavage) and were assigned to vehicle, apocynin (2.5mmol/L p.o.), catalase (10,000U/kg/day i.p.) or apocynin plus catalase for 14 days. Renal functional and hemodynamic parameters were measured every week, and kidneys were harvested at the end of the study for histological and NADPH oxidase 4 (NOX4) assessment. Oxidative stress markers and blood urea nitrogen (BUN) were measured. CsA rats had higher plasma malondialdehyde (by 340%) and BUN (by 125%), but lower superoxide dismutase and total antioxidant capacity (by 40%, all P<0.05) compared to control. CsA increased blood pressure (by 46mmHg) and decreased creatinine clearance (by 49%, all P<0.05). Treatment of CsA rats with apocynin, catalase, and their combination decreased blood pressure to near control values (all P<0.05). NOX4 mRNA activity was higher in the renal tissue of CsA rats by approximately 63% (P<0.05) compared to controls but was reduced in apocynin (by 64%), catalase (by 33%) and combined treatment with apocynin and catalase (by 84%) compared to untreated CsA rats. Treatment of CsA rats with apocynin, catalase, and their combination prevented hypertension and restored renal functional parameters and tissue Nox4 expression in this model. NADPH inhibition and H2O2 scavenging is an important therapeutic strategy during CsA nephrotoxicity and hypertension

Contribution of a1-adrenoceptor subtypes in renal hemodynamics and functions of rats with renal impairment : alteration of g-protien linked to shift in the functionality And expression of renal a1-adrenoceptor subtypes.

This study investigated the role of a 1-adrenoceptors subtypes in the regulation of renal haeamodynamics at the level of renal resistance vasculature. It is hypothesized that a 1- adrenoceptor subtype(s) distribution depends on pathophysiological states of animal. Thus, the functional role of a 1-adrenoceptor subtype(s) on renal haeamodynamics of rats with renal failure, diabetic nephropathy and cardiac hypertrophy was investigated along with the Go proteins expression in the kidney and heart of normal rats and that of rats with impairments. Kajian ini menyiasat peranan adrenoseptor subjenis a1 dalam pengawalaturan hemodinamik ginjal di peringkat rintangan vaskulatur ginjal. Adalah dihipotesis bahawa distribusi adrenoseptor subjenis a1 bergantung kepada keadaan patofisiologi haiwan. Oleh itu, peranan fungsi adrenoseptor subjenisa 1 ke atas hemodinamik ginjaJ telah dikaji dalam tikus dengan kegagalan buah pinggang, nefropati diabetes dan hipertropi jantung bersama-sama dengan ungkapan protein Go dalam buah pinggang dan hati tikus biasa dan tikus dengan kecacatan