Pharmacological and toxicological investigations of etodolac loaded gum katira microspheres prepared by W1/O/W2 emulsion solvent evaporation technique in rats

ABSTRACT Etodolac is a non-steroidal anti-inflammatory drug (NSAID) and approved by USFDA as a COX2 inhibitor. Although etodolac therapy provides clinical benefits, it is associated with upper gastrointestinal (GI) tract complications also. Etodolac loaded gum Katira microsphere (ELGKM) was prepared by W1/O/W2 emulsion solvent evaporation technique. The gastric irritation properties of orally administered pure etodolac, ELGKM and blank microspheres (without etodolac) were evaluated in experimental rats treated for 6 days. The stomach examination and biochemical investigation of stomach tissue of treated rats indicated that ELGKM formulation remarkably reduced ulcerogenecity as compared to pure etodolac. The anti-inflammatory activities of pure etodolac and ELGKMs were ascertained by the implantation of cotton pellets in rats for 6 days. Based on the results, ELGKMs showed significant anti-inflammatory activities (P<0.01) as compared to control group. The cotton pellets test suggested that ELGKM formulation retained more anti-inflammatory properties among the groups. The hematological changes, biochemical analysis and histopathological studies of subacute toxicity in rats revealed that ELGKM were the effective sustained release formulation in the treatment of chronic pain and inflammation. In conclusion, the physicochemical characterization, pharmacological and toxicological studies suggest that ELGKMs may represent as a potential candidate for sustained drug delivery (10-12 hours) in chronic joint pain related diseases with remarkably diminished gastrointestinal side effects.

Acceleration of skin wound healing with tragacanth [Astragalus] preparation: an experimental pilot study in rats

Gum tragacanth is a natural complex mixture of polysaccharides and alkaline minerals extracted from species of Astragalus plant, which is found widely in arid regions of the Middle East. In a pilot experimental study we examined the effects of its topical application on wound healing in ten albino adult male rats. Two similar parasagittal elliptical full-thickness wounds [control vs. test samples] were created on the dorsum of each animal. Test group samples were fully covered by a thin layer of gum tragacanth daily. The extent of wound healing was evaluated by planimetric analysis on multiple occasions during the 10-day study period. On the 7[th] day of the study, the percent of wound closure was significantly higher in gum tragacanth-treated specimens compared to the control samples [87% +/- 2% vs. 70% +/- 4%, P<0.001]. The majority of wounds in the test group were completely closed by the 10[th] day of the study. The difference in wound healing index measured by histological examination on day 10 of the study was also statistically meaningful between the two groups [0.624 +/- 0.097 vs. 0.255 +/- 0.063, P<0.05]. The results of this study clearly showed the useful effects of topical application of gum tragacanth in acceleration of skin wound contraction and healing. More studies are encouraged to identify the implicating agents and precisely understand the mechanism by which they exert their wound healing effects

[Studies on the electrostatic interactions between beta -lactoglobulin and tragacanthin: the first step towards fabrication of biopolymeric micro- and nanoparticles]

Investigation of the colloidal behaviour of protein-polysaccharide systems is becoming increasingly important to provide a foundation for their applications in areas such as production of biopolymer micro-and nano-particles, designing food analogues, and microencapsulation technology. The aim of the present study was to investigate the pH-induced critical transitions during associative phase separation between beta -lactoglobulin [BLG] and tragacanthin [T]. The formation of electrostatic complexes in BLG/T dispersions [0.3wt.% total concentration; BLG:T ratio 2:1] was investigated as a function of pH [2.00-6.00] by spectrophotometry and particle size analysis. In addition, coupling of slow in situ acidification of the blend, with gluconodelta-lacton, and rheometry were used to monitor the structural transitions during the associative phase separation. The influence of salt type and concentration on the formation of micro-particles were also determined. The formation of soluble complexes started at pH -5.20, and at pH -4.85 the aggregation of intrapolymeric complexes occurred, followed by a bulk phase separation at pH -4.30. The data indicated that coacervation occurred at pH 4.15. Finally, the mixture returned to a mono-phasic system at pH 2.5. Particle size analysis showed that the assembled structures experienced a contraction process upon complexation. Rheometry provided deeper insights into the colloidal behaviour of the system and the results were in good agreement with quiescent pH-induced transitions established by HCl titration. The formation of the micro-particles was strongly salt-dependent. Under controlled pH conditions, electrostatic interactions between beta -lactoglobulin and tragacanthin can be used to form a variety of biopolymer particles. These biopolymeric micro- and nanoparticles may be used in the food industry as natural delivery systems or fat-replacers

[Effects of blanching and hydrocolloid coating of potatoes with methyl cellulose and tragacanth on French-fries oil uptake and qualitative properties]

French fries are a food product with an upward consumptuion trend in Iran. Because of high oil uptake during frying, French fries are an energy-dense food item, providing a very large number of calories to the body. Therefore, efforts to reduce the rate of oil uptake by this popular food item would contribute to the public's health. The purpose of this study was to determine the effects of blanching and coating of potatoes with methyl cellulose and tragacanth on French-fries oil uptake and qualitative properties. Strips of potato [Agria variety] were prepared, blanched in water or a calcium chloride solution [0.5%], coated with a solution of methyl cellulose [0.5, 1.0 and 1.5%], tragacanth [0.5, 1.0 and 1.5%], methyl cellulose [0.5, 1.0 and 1.5%] and sorbitol [0.5%], or tragacanth [0.5, 1.0 and 1.5%] and sorbitol [0.5%] and deep-fried. Oil uptake, moisture content, and color of the French fries were measured and their sensory properties determined and compared with those of control samples. Blanching and hydrocolloid coatings of the samples brought about a decrease in oil uptake and increases in moisture content and texture tenderness of the potato strips [p<0.01]. Blanching in calcium chloride alone reduced oil uptake by 8.61%. In comparison with the control samples, coating with methylcellulose [1.5%] with sorbitol [0.5%] decreased oil uptake from 19.85% to 16.29%. Blanching in calcium chloride resulted in a significant 5%increase in moisture content. The hydrocolloid coatings caused significant increases in moisture content and resistance to cutting of the samples [P<0.01], such that the highest moisture content [44.60%] was obsereved in the samples coated with methyl cellulose [1.5%]. Tragacanth at aconcentartion of 1.5% with sorbitol at a concentartion of 0.5% brought about the highest resistance [211/13 Newton] to cutting. The findings also showed that hydrocolloid coatings resulted in significant incremets in the L [asterisk] b [asterisk], a [asterisk] factors of the French fries color as compared to the control samples. However, there were no significant differences among samples with regard to sensory characteristic

Preparation and in-vitro in-vivo evaluation of sustained release matrix diclofenac sodium tablets using PVP-k90 and natural gums

Conventional dosage form is nowadays mostly replaced by sustained release formulation in order to increase drug efficacy and patient compliance. The sustained release properties of the PVP K90 alone and in combination with guar gum, xanthan gum and gum tragacanth were evaluated using diclofenac sodium [100 mg/tablet] as a model drug. Tablets were processed using wet granulation method and evaluated for sustained drug release properties. The drug release from the formulations was studied in relationship with Commercially available Diclofenac Sodium SR, used as a reference tablets and results were expressed as similarity [f1] and differential factor [f2]. The tablets prepared using PVP K90 160 mg/tablet sustained the release of diclofenac sodium for 12 hours. Formulations where the PVP K90 was partially replaced with different gums also sustained the release of drug for 12 hours. The release of the drug from these formulations mainly followed Higuchi model and super case-II and Non-Fickian diffusion. The in-vivo drug release was studied in healthy human volunteers using non-blinded cross over, two period design using Diclofenac Sodium SR Tablets as a reference drug. The relative bioavailability of the formulation containing PVP K90 and gum tragacanth was 0.91. The studies showed that the use of the PVP K90 in combination with gum tragacanth both in-vitro and in-vivo sustained the release of the drug

[Efficiency and mechanism of action of hydrocolloids in preventing serum separation in Doogh]

Doogh is a kind of Iranian fermented dairy-based drink produced by adding water and salt to yoghurt. The major problem of this product is serum separation during storage, because of its low pH and aggregation of caseins. In the present study, the efficiency of some hydrocolloids in preventing serum separation as well as the stabilization mechanism of gum tragacanth-a local gum-were investigated. The effects of high-methoxyl pectin, tragacanth, and locust bean gum at different concentrations, individually and in combined forms, tragacanthin, and soybean soluble polysaccharides type M, on the stability of sour Doogh were investigated. In addition, the influence of gum tragacanth and locust bean gum on the stability of prebiotic Doogh [containing inulin] was also studied. In each case the duration of the study was 30 days. In order to elucidate the stabilization mechanism of gum tragacanth, the rheological properties, zeta potential, and microstructural characteristics of the stabilized Doogh samples were measured. According to our findings, tragacanthin, tragacanth and locust bean gum could inhibit serum separation for 30 days at a concentration of 0.1, 0.2 and 0.3%, respectively, while type M soybean soluble polysaccharides caused the stabilization at a concentration of 0.6% only for 6 days. Furthermore, combinations of gum tragacanth and locust bean gum were also effective in fully stabilizing Doogh [at a concentration of 0.15% and ratios of 80:20 and 50:50]. Inulin was not effective in stabilizing the sour Doogh samples. However, tragacanth and locust bean gums inhibited serum separation in prebiotic Doogh. Based on our findings, the most suitable rheological model for the control samples and the samples containing hydrocolloids were the Newtonian and Power law, respectively. Based on the results of this study, tragacanthin [the water-soluble part of gum tragacanth] seems to have a major role in stabilizing Doogh, probably by being adsorbed onto caseins [via electrostatic and steric repulsion]. On the other hand, bassorin [the water-insoluble part of gum tragacanth] may help stabilization by increasing viscosity. Therefore, gum tragacanth could be strongly recommended to be used as an adsorbing hydrocolloid in sour Doogh to inhibit serum separation

Effect of Nelumbo nucifera rhizome extract on the gastrointestinal tract of rat.

Extract of Nelumbo nucifera rhizome (RNN) was used as anti-diarrheal agent to combat the diarrhea in experimental rats. The RNN extract in graded doses (100, 200, 400 and 600 mg/kg body wt.) reduced not only the frequency of defecation, wetness of fecal dropping and PGE2 induced enteropooling but also the propulsive movements of charcoal meal significantly.