Effects of oil and drug concentrations on droplets size of palm oil esters (POEs) nanoemulsion.

Aim of the present work is to study the effects of oil and drug concentrations on droplets size of a nanoemulsion. Newly introduced oil, palm oil esters (POEs) by Universiti Putra Malaysia researchers was selected for the oil phase of the nanoemulsion, because the oil was reported to be a good vehicle for pharmaceutical use. Nanoemulsions were prepared with different concentrations of oil and drug and their effects on droplets size were studied by laser scattering spectroscopy (Nanophox). The results of droplets size analysis shows the droplets size increase with increasing concentration of oil and drug concentrations. It can be concluded from this study, that oil and drug concentrations have an effect on the droplets size of POEs nanoemulsion system.

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 limonene on permeation enhancement of ketoprofen in palm oil esters nanoemulsion.

This study sets out to investigate the in vitro permeation of ketoprofen from the formulated nanoemulsions through excised rat skin. In vitro permeation of ketoprofen nanoemulsion through rat skin was evaluated in Franz diffusion cells and compared with marketed product (Fastum gel). Limonene which has been reported to be a good enhancer for ketoprofen was selected. Moreover the effects of limonene which was added to the nanoemulsion formulations at levels of 1%, 2%, 3% and on rat skin permeation of ketoprofen were also evaluated. The selected optimized formulation was further studied for skin irritation. Utilization of limonene as a penetration enhancer increased the permeation of ketoprofen from the formulated nanoemulsion with increasing concentrations of limonene. The results obtained showed that nanoemulsion with 3% limonene produced similar and comparable skin permeation of ketoprofen with marketed formulation and the skin irritation study on rats showed the optimized formulation prepared was safe.

Formulation and in vitro evaluation of ketoprofen in palm oil esters nanoemulsion for topical delivery.

The aim of the present study is to formulate and investigate the potential of nanoemulsion formulation for topical delivery of ketoprofen. In this study, Palm Oil Esters (POEs) a newly introduced oil by Universiti Putra Malaysia researchers was chosen for the oil phase of the nanoemulsion, because the oil was reported to be a good vehicle for pharmaceutical use. Oil-in-water nanoemulsion was prepared by spontaneous emulsification method. The droplets size was studied by laser scattering spectroscopy (Nanophox) and Transmission Electron Microscopy (TEM). Franz diffusion cells were used, to determine the drug release and drug transferred through methyl acetate cellulose membrane (artificial membrane). The results of droplets size analysis shows the droplets are in the range of nanoemulsion which is below than 500 nm. The in vitro release profile shows a sufficient percentage of drugs released through the methyl acetate cellulose membrane. This initial study showed that the nanoemulsion formulated using POEs has great potential for topical delivery of ketoprofen.

Bioequivalence evaluation of two different formulations of ciprofloxacin tablets in healthy volunteers.

INTRODUCTION: A bioequivalence study of two oral formulations of 500 mg tablets of ciprofloxacin (RAZA Pharmaniaga, Malaysia) as test and Ciprobay (Bayer AG, Germany) as reference, was carried out in 24 healthy human volunteers. Each volunteer received a single dose of ciprofloxacin. METHODS: The study method used was a double-blind, two-period, two-treatment, two-sequence, and crossover randomised design. Blood samples were taken before, and within 24 hours after drug administration. Plasma concentrations of ciprofloxacin were determined by a high-performance liquid chromatographic method with ultraviolet detection. The pharmacokinetic parameters, C(max) and T(max), were obtained directly from plasma data, k(e) was estimated by log-linear regression, and the area under the curve (AUC) was calculated by the linear trapezoidal rule. The parameters, AUC(0-infinity) and C(max), were tested for bioequivalence after log-transformation of data, while the differences of T(max) were evaluated nonparametrically. RESULTS: When AUC(0-infinity) and C(max) were analysed using analysis of variance, no statistically significant difference was observed between the two different formulations. The 90 percent confidence intervals of the mean values for the test/reference ratios were 0.95-1.07 for AUC(0-infinity) and 0.90-1.07 for C(max), respectively. Both of these values were within the bioequivalence acceptance range of 0.80-1.25. CONCLUSION: We found that both formulations are bioequivalent and, therefore, interchangeable.

The effect of niosomes and polysorbate 80 on the metabolism and excretion of methotrexate in the mouse.

The effect of non-ionic surfactant vesicle (niosome) encapsulation on the metabolism and urinary and faecal excretion of methotrexate (MTX) in mice has been studied following oral and intravenous administration, and compared with the effects of co-administration of free drug and polysorbate 80, which does not form vesicles. Niosome entrapment reduces the excretion of MTX into urine and bile whereas polysorbate 80 increases its excretion. Monitoring of the levels of MTX and its 7-hydroxy metabolite indicates that entrapped MTX is protected from rapid metabolism in vivo, particularly in niosomes but to a small degree in the micellar systems formed by polysorbate.

The effect of non-ionic surfactant vesicle (niosome) entrapment on the absorption and distribution of methotrexate in mice.

Non-ionic surfactant vesicles (niosomes) prepared from a non-ionic surfactant, cholesterol and dicetyl phosphate and containing methotrexate (MTX) have been administered to mice. Given intravenously the niosomes prolong the levels of MTX in the blood, large amounts of the drug being taken up by the liver. There was also an increased uptake of MTX into the brain, perhaps due to an effect of the niosome components on the permeability of the blood brain barrier. Absorption of the drug from the gastrointestinal tract following oral ingestion, appeared to be increased at some doses; most of the entrapped MTX was taken up by the liver, but uptake of MTX into the brain was also increased. The metabolic profile of the drug is altered by the niosomes which appear to prevent the rapid formation of 7-hydroxy methotrexate.

The distribution and elimination of methotrexate in mouse blood and brain after concurrent administration of polysorbate 80.

This paper describes further exploration of the effect of polysorbate 80 on the absorption, distribution, and elimination of methotrexate (MTX). This study has confirmed the earlier finding that polysorbate 80 could increase the absorption of MTX from the mouse gastrointestinal tract and enhance the drugs uptake into the brain. The experiments reported here suggest that polysorbate 80 has a direct effect on the blood-brain barrier leading to the increased uptake of MTX, which is evident following IV administration. Measurements of MTX excreted in the urine and faeces confirmed the role of polysorbate 80 in facilitating the excretion of MTX into the bile and urine. Polysorbate 80 administered PO did not cause any reduction of plasma volume, thus excluding the possibility that the higher MTX concentrations measured in mice after concurrent administration of polysorbate PO might result from a reduction in blood volume due to osmotic effects. At the doses given, polysorbate 80 appeared not to have a damaging effect on the gastrointestinal mucosa.

Effects of polysorbate 80 on the absorption and distribution of oral methotrexate (MTX) in mice.

This study is part of a programme of work aimed at improving the bioavailability of oral methotrexate (MTX). In preliminary experiments no significant effect of non-ionic surfactant polysorbate 80 (Tween 80) on absorption of 0.5 mg MTX X kg-1 in NMRI mice was observed except when the drug was given together with 6% polysorbate 80 in solution. Absorption from a higher dose of 3 mg MTX X kg-1 was increased when the drug was administered with 2% or 6% polysorbate 80. Plasma MTX measurements confirmed the significantly higher levels of MTX with 6% polysorbate 80 PO. In subsequent experiments, when Porton mice were used and 4 mg MTX X kg-1 was administered PO, higher plasma and brain levels of MTX were measured in animals given the drug with 6% polysorbate 80, suggesting the enhancement of MTX uptake by this non-ionic surfactant. Although the amount of MTX in the liver and kidney of mice given MTX with polysorbate 80 were not significantly different from the amounts in mice given MTX alone, the lower observed levels suggested that polysorbate 80 perhaps facilitates the elimination of the drug from these organs. The amount of plasma MTX in mice measured 1 h after oral administration of various MTX doses in the presence of 6% polysorbate 80 were significantly higher than the levels in mice given the drug without surfactant, but the significantly higher amounts of MTX in the brain were only observed following the doses of 2 and 6 mg MTX X kg-1.