FORMULATION, EVALUATION, AND IN VIVO ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES OF MORINGA GRANULES

Objective: Consumption of crude natural products like plants and herbs for mitigation or treatment of illnesses usually accompanied with inconsistent therapeutic effects because of poor solubility and low bioavailability of active phytochemical(s) in addition to product instability. To overcome all of above mentioned drawback ethanol extract of Moringa oleifera leaf was formulated as standardised solid dosage form. Methods: Different types of materials as an adsorbent, surfactant and other necessary excipients were tested to be use in formulation of Moringa granules utilising wet granulation method. The formulated Moringa granules was then evaluated for organoleptic properties and physical characteristics, in vitro dissolution test, compatibility, drug content, heavy metal tests and microbial limit tests. Additionally, the in vivo anti-inflammatory against Carrageenan-induced paw oedema and anti-arthritic activity against CFA-induced arthritis were also assessed. Results: 95% ethanol extract of M. oleifera leaves was successfully formulated as standardised granules for oral administration utilising simple and low-cost techniques. Dissolution rate for the marker compounds was increased by an average of 1.076 fold. Animal groups given the prepared Moringa granules showed an improvement in the anti-inflammatory activity and the anti-arthritic activity compared to animal groups given crude extract at the same dose level. Additionally, all the treatment groups showed a significant difference at P<0.05 and P<0.01 compared to control group. Conclusion: To the best of our knowledge, this work was the first to use gum Arabic in the formulation of a standardised botanical pharmaceutical dosage form of M. oleifera crude extract. Additionally, formulation of Moringa granules apparently improves the drug release profile and bioactivity compare to Crude Moringa extract

Anti-diabetic activity-guided screening of aqueous-ethanol Moringa oleifera extracts and fractions: Identification of marker compounds

Purpose: To explore the anti-diabetic effects of Moringa oleifera extracts and  fractions, and to identify their active/marker compounds.Methods: Five different aqueous ethanol extracts (95, 75, 50, 25 %v/v and 100 % water) of Moringa oleifera were given orally to normal rats to assess their hypoglycemic activities and effect on intraperitoneal glucose tolerance test (IPGTT) data. Rats with streptozotocin-induced diabetes were used to assess acute and sub-chronic anti-hyperglycemic activities. The most active extract was further subjected to liquid-liquid fractionation into hexane, chloroform, ethyl acetate,  butanol, and water; these fractions were screened for anti-diabetic activities. The most active extract, and fractions thereof, were then subjected to qualitative and quantitative phytochemical analysis. Standardization was achieved via thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC), and used to identify marker compounds.Results: Of all the extracts and fractions, 95 % (v/v) ethanol extract (at 1,000 mg/kg) and the butanol fraction thereof (at 500 mg/kg) were the most active,  reducing blood glucose concentration after onetime (acute) administration to  diabetic rats (p < 0.01). No significant hypoglycemic activity was apparent, and the materials had no effect on IPGTT performance by normal rats. TLC and HPLC  identified quercetin 3-β-D-glucoside, kaempferol-3-O-glucoside, and cryptochlorogenic acid.Conclusion: An M. oleifera leaf extract exhibited anti-hyperglycaemic activity in diabetic rats only. This effect was likely attributable to cryptochlorogenic acid, quercetin 3-β-D-glucoside, and kaempferol 3-Oglucoside. Keywords: Anti-diabetic, Moringa oleifera, Cryptochlorogenic acid, Quercetin 3-β-D-glucoside, Kaempferol 3-O-glucoside, Streptozotoci

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

An investigation into the use of lipid matrices for the controlled release of therapeutic agents

Gelucires are pharmaceutical excipients made from hydrogenated vegetable oils and polyglycolised fatty acids. The variety of components within the gelucire can result in complex carrier characteristics ranging from the polymorphic changes of the lipid components to the interaction of the incorporated drugs with one or more carrier components. The effects of adding two different model drugs on the structure of Gelucire 50/13 and the influence of the drug loading were established. Thermal analysis techniques such as Hot-Stage Microscopy (HSM) and Differential Scanning Calorimetry (DSC) were utilised for morphological and structural studies. These techniques showed that the addition of paracetamol caused a marked change to the DSC thermal profile by stabilising the lowest melting form of the gelucire whereas caffeine did not significantly affect it. Dissolution studies were performed and the mechanisms of release were determined from the fitting of mathematical models to the release data. Additionally, results from erosion and water uptake studies performed by physically measuring the extent of each process on the matrices were found to be related to those obtained by mathematical fitting. A difference in the contributions of erosion and diffusion to drug release arose due to the different drugs added. The loadings of drug did not greatly affect the parameters studied. The effects of ageing the matrices at two different temperatures and at various time intervals were also investigated. In addition to the techniques above, Scanning Electron Microscopy (SEM) was also performed and it was found that the addition of a sterically compatible emulsifier such as sorbitan monostearate inhibited the blooming of stable crystals on the surfaces of the matrices. It was also found that storage at a higher temperature tempered the matrices to a more stable form and the extent of the ageing effect was also influenced by the drug incorporated. (author)Available from British Library Document Supply Centre- DSC:DXN057394 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

A review on promising phytochemical, nutritional and glycemic control studies on Moringa oleifera Lam. in tropical and sub-tropical regions

Plants have provided sources to find novel compounds. These plants are being used as therapeutic purposes since the birth of mankind. The traditional healers normally utilize medicinal plants as crude drugs while scientists using the folk claim as guides to explore medicinal plants. Moringa oleifera is a famous edible plant having therapeutic and nutritive values. The present study was designed to cumulate the research data regarding to what extent, phytochemical, nutritional and glycemic control studies has been explored using its different extracts. The articles indicated that the powder, aqueous, methanol and ethanol extracts of Moringa oleifera (leaves, pods, seeds, stem and root bark) have significant therapeutic herbal potential to treat diabetes mellitus. Collectively, the mechanism behind is intestinal glucose inhibition, insulin release as well as decrease in insulin resistance probably regeneration of β-cells of pancreas, increase in glutathione and reduction in malondialdehyde. Conclusively, this article give descriptive information about antidiabetic effect, claimed marker compounds and proposed antihyperglycemic mechanism of a single plant. It can be suggested a potential herbal source to treat diabetes mellitus as being widely accepted by major population as nutrition and therapeutic agent

Formulation and In Vivo Evaluation of a Solid Self-Emulsifying Drug Delivery System Using Oily Liquid Tocotrienols as Model Active Substance

Self-emulsifying drug delivery systems (SEDDS) can improve the oral bioavailability of poorly water-soluble drugs. Solid self-emulsifying drug delivery systems (s-SEDDS) offer several advantages including improved drug stability, ease of administration, and production. Most compounds employed in developing s-SEDDS are solid in nature, with a high amount of surfactants added. The aim of this study was to develop an s-SEDDS using a tocotrienol-rich fraction (TRF) as the model liquid active substance via a simple adsorption method. The solid formulation was developed using magnesium aluminosilicate as the carrier with 70% TRF and 30% surfactants (poloxamer and Labrasol®). The formulation showed good self-emulsification efficiency with stable emulsion formed, excellent powder flowability, and small emulsion droplet size of 210–277 nm. The s-SEDDS with combined surfactants (poloxamer and Labrasol®) showed a faster absorption rate compared to preparations with only a single surfactant and enhanced oral bioavailability (3.4–3.8 times higher) compared to the non-self-emulsifying oily preparation when administered at a fasted state in rats. In conclusion, an s-SEDDS containing a high amount of TRF was successfully developed. It may serve as a useful alternative to a liquid product with enhanced oral bioavailability and the added advantage of being a solid dosage form

Studies On The Mechanisms Of Antihyperuricemic Activity, Chornic Toxicity And Formulation Of Phyllanthus Niruri Lignans For The Development Of Potential Antihyperuricemic Agents

In-situ polymerization technique was used to prepare epoxy/organo-montmorillonite (OMMT) nanocomposites by three different mixing sequence methods. The mechanical and morphological properties of epoxy/ OMMT nanocompositeE were studied by flexural tests, fracture toughness (SENB), Scanning Electron Microscopy (SEM) and X-ray Diffraction (XRD). The flexural modulus of epoxy was improved significantly by the incorporation of OMMT. This is attributed to the reinforcement and exfoliation/intercalation of the OMMT. The XRD results showed the formation of exfoliated structure in the epoxy/OMMT nanocomposites. Sequence of mixing influenced the dispersion and intercalation/exfoliation of the OMMT in the epoxy matrix. Appropriate mixing sequence should be selected in order to achieve better exfoliation of OMMT and higher flexural modulus and strength of the epoxy nanaocomposites. In this study, computer aided statistical methods of experimental design (Response Surface Methodology, RSM) was used to investigate the process variables on the flexural properties of epoxy/OMMT nanocomposites. Speed of mechanical stirrer, post-curing time and post-curing temperature were chosen as process variables in the design experimental. Results showed that the speed of mechanical stirrer post-curing time and post-curing temperature were able to influence the flexural modulus and flexural yield stress of epoxy/OMMT nanocomposites

Enhanced oral bioavailability and intestinal lymphatic transport of a hydrophilic drug using liposomes

A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph ( collected from the mesenteric lymph duct) and in plasma ( collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph

A SIMPLE (HPLC–UV) METHOD FOR THE QUANTIFICATION OF COLCHICINE IN BULK AND ETHOSOMAL GEL NANO-FORMULATION AND ITS VALIDATION

Objective: To develop and validate a stability-indicating reversed phase high-performance liquid chromatography (RP-HPLC) method for the determination of colchicine in bulk and ethosomal gel nano-formulation.Methods: The chromatographic conditions were optimized using stainless steel Hypersil Gold C-18 analytical column with the dimensions of 250 mm x 4.6 mm ID x 5 µm. The mobile phase consisted of acetonitrile and ammonium acetate buffer (20 mmol/l, pH=4.85) in the ratio of 32:68 v/v. The flow rate was set at 1 ml/min and the detection wavelength was 353 nm. The column was maintained at 30 °C and the injection volume was 10 µl. The stability of colchicine in different conditions was investigated by exposing the drug to stress degradation using acid, base, oxidation, heat and light.Results: There was no interference from excipients, impurities, dissolution media or degradation products at the retention time of colchicine 5.9 min indicating the specificity of the method. The limit of detection (LOD) and the limit of quantification (LOQ) were 8.64 ng/ml and 26.17 ng/ml respectively. The drug showed good stability under heat, acid, oxidation and light, but substantial degradation was observed under alkali condition. The procedure was validated for specificity, linearity, accuracy and precision.Conclusion: A simple, rapid, specific and stability-indicating HPLC–UV method for the determination of colchicine in the pure and ethosomal gel was successfully developed. The developed method was statistically confirmed to be accurate, precise, and reproducible