The Antidiabetic Effects of The Bioactive Flavonoid (Kaempferol-3-O-ß-D-6{P- Coumaroyl} Glucopyranoside) Isolated From Allium cepa.

BACKGROUND: Allium cepa has been in use in traditional medicine in the treatment of diabetes mellitus. The aqueous and ethanolic extracts have been found effective in lowering blood glucose levels in experimental diabetic rats and guinea pigs. METHODS: The study was carried out to isolate the active principle responsible for the observed hypoglycaemic effect in experimental animals. Freeze-dried aqueous extract of Allium cepa was separated into various fractions using column chromatography with silica gel as a stationary phase. The column was eluted with various ratios of mixtures of hexane, chloroform, ethyl acetate and methanol. These column fractions obtained were tested for hypoglycaemic effects in alloxan-induced diabetic male rats. The identified active fraction was further separated by means of preparative thin layer chromatography (P-TLC) using silica gel as stationary phase and mixture of solvents chloroform, ethyl acetate, and methanol in the ratio of 10: 4: 1 respectively as the mobile phase. Pre-coated P-TLC plates were used and the fraction bands were identified under u.v. lamp and by spraying with concentrated sulphuric acidvanillin reagent. The isolated bands (Rf 0.438) were scrapped off from the P-TLC plates, redissolved in absolute methanol, filtered and concentrated to dryness. RESULTS: The isolated compound's structure was determined be means of one and two dimensional nuclear magnetic resonance spectroscopy as well as comparison with literature data. The isolated compound given at 25 mg/kg dose reduced blood glucose in diabetic rats in manner which was comparable to the effect obtained with 2 mg/kg of glibenclamide (p < 0.05). The structure of the compound was found to be that of kaempferol- 3-O-ß - D 6{P-coumaroyl} glucopyranoside. CONCLUSION: The research findings have supported the claims that extracts of Allium cepa possess glucose lowering properties in experimental diabetic animals.

Some pharmacological properties of Synclisia scabrida II.

The effect of the aqueous extract of S. scabrida on behaviour, and as an analgesic and antiulcer agent were studied. The extracts did not produce significant central nervous system action, or analgesia but had significant antiulcer activity against aspirin induced ulcer. The extract showed anticholinergic and antihistaminergic properties.

Antimicrobial activity of Pterocarpus osun stems.

Phytochemical and antimicrobial screening of extractives from Pterocarpus osun elder stems showed significant activities due to different classes of new-isolated constituents.

Plasma and saliva concentrations of rifampicin in man after oral administration.

The saliva and plasma concentrations of rifampicin were determined following oral administration of 600 mg of the drug to healthy human subjects. Rifampicin is a zwitterion with PKa's of 1.7 and 7.9. The saliva-plasma concentration ratios calculated on the basis of the PKa of 1.7 was 1.6346. The saliva concentrations were much higher than the MICs of a variety of organisms, indicating the possible usefulness of rifampicin in the treatment of susceptible oropharyngeal and nasopharyngeal pathogens. After 24 hrs, when rifampicin was completely absent in the urine, the saliva and plasma concentrations also had fallen almost to zero.

Carbon black (N220): a possible role in poison management.

The adsorptive capacities of locally produced carbon black (N220) and activated charcoal in the management of poisoning due to some locally used drugs were investigated. Adsorption of metronidazole and tinidazole to carbon black (CB) and activated charcoal (AC) was completed within 30 min of incubation and was found to be dependent on the quantities used CB-B50 for metronidazole and tinidazole were 132.7 and 112.2 mg while AC-B50 for the two drugs were 254.7 and 125.9 mg, respectively. In the in-vivo study, 20 mg/kg of chloroquine given orally, then followed with 1.6 g/kg of either CB or AC by the same route, gave optimal protection against death in mice. The mortality rate decreased as the amount of adsorbents increased. We suggest that carbon black may be beneficial when properly handled and adequately administered during overdosage or accidental poisoning by metronidazole, tinidazole, or chloroquine.

Effect of activated charcoal on rifampicin absorption in man.

The effect of activated charcoal (AC) on rifampicin excretion was investigated in six healthy volunteers. On three occasions, at weekly intervals, each subject received a 600 mg rifampicin with 350 ml of water; b+c one and two weeks later, 600 mg of rifampicin plus 7.5 and 15 g AC, respectively, in 350 ml of water as a charcoal slurry. Urinary levels of rifampicin were measured form 1-36 hr after ingestion. Treatment with AC led to 1.2 per cent urinary recovery of rifampicin; decreased excretion rate; and a much lower plateau indicative of reduced absorption.

Adsorption studies of ciprofloxacin: evaluation of magnesium trisilicate, kaolin and starch as alternatives for the management of ciprofloxacin poisoning.

In vitro experiments were performed to investigated the extend of adsorption of ciprofloxacin to kaolin, magnesium trislilicate and to a starch obtained from the tubers of Tacca involucrata (Tacca starch) and to explore the effect of varying pH on this adsorption. Activated charcoal, a standard adsorbent and antidote in the management of poisoning due to a variety of chemical agents was employed as a comparing standard. The results of the study indicate that kaolin and magnesium trisilicate adsorbed ciprofloxacin effectively while the adsorption of the drug on the starch was relatively low. Adsorption was dependent upon the quantity of the adsorbed used. Kaolin or magnesium trisilicate could serve as an effective antidotal alternative to activated charcoal in the management of ciprofloxacin poisoning. Except in cases of poisoning due to ciprofloxacin, the concurrent administration of the drug with kaolin or magnesium trisilicate may be contraindicated. Tacca starch, however, may not really be recommended for the management of ciprofloxacin poisoning.

Use of acryclic and metacrylic acid derivatives as sustained release matrices for theophylline hydrate tablets.

Carbopol 941, an acrylic acid polymer and "Eudragit L100-55, a metacylic acid polymer, were compared as sustained release matrix devices for theophylline hydrate tablets. The theophylline tablets containing 0 to 30% of either of the polymer were prepared using the direct compression method. In vitro drug release studies were carried out in 0.1 N HCl, simulated gastric fluid without pepsin (SGF) and simulated intestinal fluid without pancreatin (SIF). A relatively prolonged release of theophylline from the two polymer matrices for an 8 hr-release period was detected. At 20% w/w and in 0.1 N HCl there were no significant drug releases from the two matrices within the first 2 hrs; after this period, carbopol 941 exerted a more retardant effect on drug releases. At 30% w/w, release rate from Eudragit L100-55 was faster for a 6 hr period with a steady state release maintained at 50% for 4 hrs. The rates of theophylline release from the matrices depended on the pH of the dissolution media and on the properties of the two matrices. While drug release from Carbopol 941 was faster in acidic media, faster release occurred from Eudragit L100-55 in alkaline medium. Drug release kinetics from the two matrices was of a general mixed order, but the first order and the diffusion-controlled mechanism were occurring simultaneously. We can conclude that carbopol 941 can be considered a better-sustained release matrix in directly compressed theophylline tablets comparing with Eudragit L100-55.

Spectrophotometric and some thermodynamic parameters of the charge transfer complexation between chloranilic acid and chlorpheniramine.

The principle of charge transfer complexation involving a pi-acceptor (chloranilic acid) and an n-donor (chlorpheniramine) was utilized in the assay of the later in its pure form and in its tablet dosage forms. Some thermodynamic parameters of the complex such as association constant (Kc), molar absorptivity (epsilon c), free energy change (delta G degree), enthalpy (delta H degree) and entropy (delta S degree) changes were determined to establish the stability of the complex and the optimum conditions for the complex formation. The values obtained for these thermodynamic parameters indicated that the complex formed between this two chemical entities is highly stable. Assay of chlorpheniramine in its pure form and in its tablet dosage forms gave high percentage recoveries. The principle of charge transfer complexation could therefore be employed in the colorimetric assay of chlorpheniramine in its tablet dosage forms.

A comparative study of modified starches in direct compression of a water soluble drug-chloroquine phosphate.

Some in vitro properties of chloroquine phosphate tablets formulated with four modified starches were investigated. The drug was formulated as tablets containing 250 mg of chloroquine phosphate and produced by the direct compression technique. The starches were isolated from maize, zea mays, rice, Oryza sativa, cassava, Manihot esculenta and cocoyam, Zanthosoma sagittifolium. They were modified through physicochemical process, Sta-Rx 1500, a directly compressible starch was used as basis for comparison. The hardness of the chloroquine tablets generally decreased to a minimum with all the modified starches at concentration level of 40% and with maximum hardness obtained when their concentrations were increased to 80%. The least hardness values were obtained with modified cocoa yam starch while the highest hardness values were obtained with modified rice starch. Modified rice and cassava starches produced chloroquine tablets that exhibited higher mechanical properties than those of modified maize starch, cocoayam starch and Sta-Rx 1500. On the basis of dissolution profile of chloroquine phosphate tablets, the modified starch samples were ranked in order of increasing dissolution as modified cocoayam maize Sta-Rx 1500 cassava rice starch sample. The release rate of chloroquine was found to be dependent on the physico-chemical properties of the individual modified starch granules such as particle size and degree of gelatinization.

In vitro properties of ciprofloxacin suppositories formulated with glycerogelatin and theobroma oil bases.

Ciprofloxacin suppositories formulated with glycerogelatin approximately nd theobroma oil bases were evaluated for in vitro bioavailability in 0.01N sodium hydroxide (pH approximately 10) and in phosphate buffer (pE- approximately 7.8). The release of ciprofloxacin from the two bases under conditions which simulated the conditions in the rectum was assessed using isolated pig rectum. The release of ciprofloxacin was faster from theobroma oil base than from glycerogelatin base using 0.01N sodium hydroxide as the dissolution medium. The cumulative amount of ciprofloxacin released was markedly reduced from each of the two bases in the presence of isolated pig's rectum and in phosphate buffer.

Effect of direct compression excipients on the stability of ascorbic acid (vitamin c) tablets.

The effects of four directly compressible excipients such as Avicel, Dipac, Ditab and Emdex on the stability of ascorbic acid tablets were evaluated. Ascorbic acid tablets were formulated by the direct compressive method at constant temperature and pressure. In vitro tablet properties such as weight uniformity, hardness, friability, moisture content, disintegration time and dissolution rate were evaluated. The tablets were also subjected to temperature and moisture stresses in order to assess their stability. The results obtained indicated that moisture and temperature affect the stability of ascorbic acid tablets. All the tablet batches exhibited very short shelf lives in the presence of the stress conditions of temperature and moisture. None of the four excipients could be recommended for use in tableting ascorbic acid based on the shelf lives.

A comparative study of modified starches in direct compression of a poorly water soluble drug (hydrochlorothiazide).

The direct compression properties of four modified starches in hydrochlorothiazide (HCTZ) tablets were studied. The starches were obtained locally from common plant sources and were modified through physicochemical treatment. Each modified starch was used as the only filler-binder-disintegrant in the formulation of hydrochlorothiazide tablets containing 25 mg of the drug. The tablets were produced by the direct compression technology. Sta-Rx 1500, a directly compressible starch, was used as basis for comparison. Evaluated tablet properties included weight and drug content uniformity, hardness and friability as well as disintegration time and dissolution profile. The modified starches exhibited species specificity in terms of the tablet properties. The weight, drug content and disintegration time for all batches of tablets were within acceptable limits. Proper ranking of the starches on the basis of specific tablet properties was used to highlight their differences.

Prediction of in vivo bioavailability of six brands of ciprofloxacin film coated tablets using the concept dissolution efficiency (DE).

A comparative in vitro dissolution efficiencies (DE) of six commercial brands of ciprofloxacin tablets were evaluated in acetic acid and phosphate buffer (pH 7.4) and results obtained were used in ranking of their probable in vivo bioavailability. The dissolution efficiencies (DE) of the six brands varied widely in the two media. This was attributed to differences in solubility of the drug in the two media. The dissolution efficiencies of five out of the six brands (Citrovenot, Ciproxin, Cipoxin, Ciproflox, and Quflox), in 0.1 N acetic acid fell within 60-75% at 30 minutes, and therefore, could be considered bioequivalent. The dissolution efficiency of a brand, Cipro, fell below 40% in the same medium and at the same sampling time and it was considered to be most likely less bioavailable in vivo. There was absence of correlation between the hardness and disintegration time of the brands with their dissolution efficiencies.

Use of dika fat in the formulation of sustained release frusemide encapsulated granules.

Sustained release frusemide granules were formulated with Dika fat, a vegetable oil extracted from the kernels of Irvingia gabonesis Var excelcia. Granules containing 60% w/w, of Dika fat and 200% w/w frusemide and lactose were prepared using the fusion method. Prepared granules (passed through 0.600 micron stainless steel sieve) were encapsulated such that each capsule contained frusemide granules equivalent to 75mg of the pure drug. Granules of same size fraction containing 10% w/w maize starch, or alginic acid and 60, 20, and 10% w/w of Dika fat, frusemide and lactose respectively were similarly prepared and encapsulated. Dissolution profiles of the encapsulated granules were assessed in 0.1 sodium hydroxide, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) without enzymes. Results obtained indicated sustained release of frusemide in the presence of Dika fat. The presence of maize starch modulated the release of frusemide while the presence of alginic acid could not show significant (P < 0.05) enhancement on frusemide release. Dissolution of frusemide was greatest in 0.1N NaOH and least in SGF. Drug release from the matrices was of mixed order with diffusion controlled mechanism and leaching process occurring together to a greater extent.

Effect of activated charcoal on isoniazid absorption in rabbits.

The effect of activated charcoal on gastrointestinal absorption of isoniazid (INH) was determined quantitatively in rabbits. The presence of activated charcoal resulted to about 40% reduction of INH bioavailability as was indicated by reduction in the AUC0-24 hour. The plasma half live (T1/2) and peak plasma concentration (Cmax) of the drug were reduced, while the apparent volume of distribution (Vd) and total clearance (Cl) of the drug were increased in the presence of activated charcoal. The results present an assessment of adsorptive capacity of activated charcoal for INH in vivo and as such could serve as a cheap, effective and readily available means of emergency treatment of INH poisoning.

Effect of hydrophilic diluents on the release profile of griseofulvin from tablet formulations.

Studies have shown that when compressing drugs with low aqueous solubility, the solubility of diluents selected is very crucial as it influences the disintegration, dissolution and bioavailability of such drugs. Based on these reports, the present study was undertaken to investigate the effect of some commonly used hydrophilic tablet diluents (lactose, sucrose, mannitol and dextrose) on the in vitro release properties of griseofulvin from compressed tablets. Griseofulvin granules and tablets were prepared using the wet granulation method. Tablet properties evaluated as a function of the diluents used include, hardness, friability, dissolution profile and dissolution efficiency at 60 min. Results obtained indicated variability in griseofulvin release in the presence of the diluents. The relative enhanced dissolution effects of the four hydrophilic diluents is in the order of dextrose>sucrose>lactose>mannitol. All the griseofulvin tablet batches produced exhibited a better drug release (in terms of rate and extent of release) than a commercially available tablet sample of griseofulvin (Fulcin(®)). The results of the dissolution efficiency (DE60min) are 91.7, 83.5, 48.7, 35.3 and 15.6% for dextrose, sucrose, lactose, mannitol and fulcin(®), respectively. The overall results indicated that dextrose or sucrose can be utilised to improve the in vitro release profile and hence in vivo bioavailability of griseofulvin from compressed tablets.

Evaluation of the fluid uptake kinetics and drug release from gellan gum tablets containing metronidazole.

In this study, the fluid uptake (swelling) kinetics and disintegrant properties of gellan gum in metronidazole tablets were evaluated in both simulated gastric and intestinal fluids (SGF and SIF respectively) without enzymes. The mechanical properties as well as the disintegration and dissolution profile of the tablets were also assessed and compared with those of two standard disintegrants: maize starch and sodium starch glycolate (Primogel). Results show that, swelling was faster and higher in SIF than SGF with the minimum and maximum swelling rates of the gum being 0.365 and 6.900 mm(3)/min respectively in SGF, while the corresponding values in SIF were 0.277 and 7.600 mm(3)/min respectively. The gum was most effective as a disintegrant for metronidazole tablets at an optimum concentration of 0.2% (w/w) when incorporated extra-granularly.

Effect of polyethyleneglycol 4000 (PEG4000) solution on the in vitro release profile of nifedipine from polymer matrices.

The effect of PEG4000 solution on the in vitro release of nifedipine, a calcium entry blocker and a poorly water soluble drug was evaluated. Nifedipine tablets containing 10 mg of nifedipine, 20% of one four polymers--Eudragit L-100 and Rs, ethylcellulose and carbopol 941, 2% lubritab and an adequate quantity of Encompress to yield 300 mg weight tablets--were formulated using the direct compression method. Tablets were compressed to a hardness of 5N, and an in vitro dissolution profile was performed on the tablets in 70% ethanol and in ethanolic PEG4000 solutions. The results obtained indicated enhancement of nifedipine release from two of the polymer matrices (Eudragit L-100 and ethylcellulose) in the presence of PEG4000 and a retardant effect from carbopol 941 matrix. It is suggested that carbopols may not be suitable for use in the formulation of nifedipine tablets since there are some physiological surfactants present in the gastrointestinal tract (GIT).