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.

Study of surface activity of piroxicam at the interface of palm oil esters and various aqueous phases.

The surface activity of some non-steroidal anti-inflammatory agents like ibuprofen was investigated extensively. This fact has attracted the researchers to extend this behavior to other agents like piroxicam. Piroxicam molecules are expected to orient at the interface of oil and aqueous phase. The aim of this study was, firstly, to assess the surface and interfacial tension behaviour of newly synthesised palm oil esters and various pH phosphate buffers. Furthermore, the surface and interfacial tension activity of piroxicam was studied. All the measurements of surface and interfacial tension were made using the tensiometer. The study revealed that piroxicam has no effect on surface tension values of all pH phosphate buffers and palm oil esters. Similarly, various concentrations of piroxicam did not affect the interfacial tensions between the oil phase and the buffer phases. Accordingly, the interfacial tension values of all mixtures of oil and phosphate buffers were considerably high which indicates the immiscibility. It could be concluded that piroxicam has no surface activity. Additionally, there is no surface pressure activity of piroxicam at the interface of plam oil esters and phosphate buffers in the presence of Tweens and Spans.

Development of a stepping force analgesic meter for a rat arthritic model.

Behavioural assessment of experimental pain is an essential method for analysing and measuring pain levels. Rodent models, which are widely used in behavioural tests, are often subject to external forces and stressful manipulations that cause variability of the parameters measured during the experiment. Therefore, these parameters may be inappropriate as indicators of pain. In this article, a stepping-force analgesimeter was designed to investigate the variations in the stepping force of rats in response to pain induction. The proposed apparatus incorporates new features, namely an infrared charge-coupled device (CCD) camera and a data acquisition system. The camera was able to capture the locomotion of the rats and synchronise the stepping force concurrently so that each step could be identified. Inter-day and intra-day precision and accuracy of each channel (there were a total of eight channels in the analgesimeter and each channel was connected to one load cell and one amplifier) were studied using different standard load weights. The validation studies for each channel also showed convincing results whereby intra-day and inter-day precision were less than 1% and accuracy was 99.36-100.36%. Consequently, an in vivo test was carried out using 16 rats (eight females and eight males). The rats were allowed to randomly walk across the sensor tunnel (the area that contained eight channels) and the stepping force and locomotion were recorded. A non-expert, but from a related research domain, was asked to differentiate the peaks of the front and hind paw, respectively. The results showed that of the total movement generated by the rats, 50.27 ± 3.90% in the case of the male rats and 62.20 ± 6.12% in that of the female rats had more than two peaks, a finding which does not substantiate the assumptions made in previous studies. This study also showed that there was a need to use the video display frame to distinguish between the front and hind paws in the case of 48.80 ± 4.01% of the male rats and 66.76 ± 5.35% of the female rats. Evidently the assumption held by current researchers regarding stepping force measurement is not realistic in terms of application, and as this study has shown, the use of a video display frame is essential for the identification of the front and hind paws through the peak signals.

Intestinal permeability studies of sulpiride incorporated into self-microemulsifying drug delivery system (SMEDDS).

The objective of the present study was to determine the intestinal absorption of sulpiride incorporated into SMEDDS by means of single-pass intestinal perfusion method (SPIP) in rat and to compare the effective permeability coefficient obtained with that of drug solution and micellar solution. The prepared SMEDDS and micelles formulations were investigated for droplets size. SPIP experiment was performed using the three formulations in three of the secluded regions of the small intestine (duodenum, jejunum, and ileum). The amount of the drug in the samples was estimated by HPLC and the effective permeability coefficients in rats were calculated. The human intestinal permeability was predicted based on rat effective permeability coefficient value. The dilution stability of the formulations was also determined. The average droplet size of SMEDDS and micelles was 9.27 nm and 7.20 nm respectively. The effective permeability coefficient of sulpiride was appreciably lower in the ileum weighed against jejunum and duodenum when administered as a solution (P<0.05). The estimated human absorption of sulpiride for the SMEDDS dilutions was superior to that from solution (P<0.05) and similar to micellar solution. The micellar dilutions were unstable whereas the SMEDDS dilutions were stable. Based on the above results, SMEDDS can be a potential candidate for improving the peroral absorption of the sulpiride.

HPLC and anti-inflammatory studies of the flavonoid rich chloroform extract fraction of Orthosiphon stamineus leaves.

The aim of the present study was to verify the anti-inflammatory activity of Orthosiphon stamineus leaf extracts and to identify the active compound(s) contributing to its anti-inflammatory activity using a developed HPLC method. Active chloroform extract of O. stamineus was fractionated into three fractions using a dry flash column chromatography method. These three fractions were investigated for anti-peritoneal capillary permeability, in vitro nitric oxide scavenging activity, anti-inflammatory and nitric oxide (NO) inhibition using carrageenan-induced hind paw edema method. The flavonoid rich chloroform extract fraction (CF2) [containing sinensetin (2.86% w/w), eupatorin (5.05% w/w) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (1.101% w/w)], significantly reduced rat hind paw edema, NO and decreased dye leakage to peritoneal cavity at p < 0.05. IC(50) of in vitro NO scavenging of CF2 was 0.3 mg/mL. These results suggest that the anti-inflammatory properties of these CF2 may possibly be due to the presence of flavonoid compounds capable of affecting the NO pathway.

Antioxidant and hepatoprotective effects of Murdannia bracteata methanol extract.

Murdannia bracteata (C. B. Clarke) is a local plant that is widely used in Malaysia as a traditional remedy for various diseases of the kidney and liver, including inflammation and cancer. In the present study, we investigated the antioxidant and hepatoprotective activities of M. bracteata methanol extract (MB). 2,2'-diphenyl-1-picrylhydrazyl radical scavenging activity, lipid peroxidation inhibition and trolox equivalent antioxidant capacity of MB were determined. The hepatoprotective activity of MB was studied using a CCl(4)-induced liver toxicity model in rats. The hepatoprotective effect was assessed by monitoring the plasma malondialdehyde level and serum alanine transaminase and aspartate transaminase activities. Histopathological changes of hepatic tissue were also investigated. The results indicated that MB possessed potential antioxidant, lipid peroxidation inhibition and free radical scavenging activities. Pretreatment of rats with MB (500 mg/kg and 1000 mg/kg per os) before induction of CCl(4)-induced hepatotoxicity showed a dose-dependent reduction in the necrotic changes in hepatic tissue. The increases in plasma malondialdehyde level, serum alanine transaminase and aspartate transaminase activities were also significantly inhibited by MB. The total phenolic content of MB determined using Folin-Ciocalteu assay was found to be 10%. The results of the present study indicated that the hepatoprotective effect of MB is most likely due to its antioxidant and free radical scavenging properties.