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.

Performance of Starch obtained from Dioscorea dumetorium as Disintegrant in Sodium Salicylate Tablets

Starch obtained from Dioscorea dumetorium was employed as a disintegrant in Sodium Salicylate based tablets at concentrations of 5 -15w/w. Properties of the starch evaluated include: bulk and tapped densities; water uptake by capillarity; Hausner's quotient and percent compressibility. Compound tablets were evaluated for hardness; friability; disintegration time and dissolution rate. Batches of tablets containing equivalent concentrations of AC-di-sol or maize starch were employed as standards. Results obtained indicate that Dioscorea dumetorium starch performed as much better as a disintegrant in sodium salicylate tablets as maize starch but less than Ac-di-sol

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.

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.

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.

Some plasma pharmacokinetic parameters of isoniazid in the presence of a fluoroquinolone antibacterial agent.

The effects of ciprofloxacin (CP), a fluoroquinolone antibacterial agent, on the extent of absorption of isoniazid (INH) and on some of its pharmacokinetic parameters were investigated in six healthy female volunteers between the ages of 23 and 32 years. The presence of CP led to increase in the amount of INH and to a slight reduction in its peak plasma concentration (Cmax). There was a 1-hour increase in the time to attain Cmax (tmax) of INH, indicating absorption interaction between the two drugs. This absorption interaction was related to inhibition of cholinergic neurotransmission caused by CP, which is capable of inhibiting gastric motility, leading to a delay in gastric emptying. The rate of elimination (K) and plasma half-life (t1/2) of INH were not significantly affected (P = 0.05). The extent of absorption interaction that may have occurred (based on values of 24-hour values for area under the concentration curve, Cmax, Tmax, K, and t1/2) was considered to be of no therapeutic consequence, and the coadministration of the two drugs may be recommended in clinical practice.

Adsorptive capacity of activated charcoal for rifampicin with and without sodium chloride and sodium citrate.

The effects of two saline cathartics (sodium chloride and sodium citrate) on the adsorptive capacity of activated charcoal (AC) for rifampicin were studied. Solutions of rifampicin alone and rifampicin with 7.5 mg/ml cathartic solution were vortex-mixed for 30 s with different quantities of AC. These were incubated for 30 min at 37 degrees C and analyzed for free rifampicin spectrophotometrically at 320 nm. The addition of sodium citrate significantly increased (p<0.05) the adsorptive capacity of AC for rifampicin with a resulting decrease in B-50 values at both the therapeutic and simulated toxic doses. Sodium chloride addition reduced the binding of rifampicin to AC at the toxic doses. The adsorption of rifampicin to activated charcoal, both alone and with the two saline cathartics, obeyed quantity-dependent kinetics. AC may be co-administered with sodium citrate in the management of rifampicin overdose.

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.

Rifampicin pharmacokinetics with and without ciprofloxacin.

We investigated the effect of ciprofloxacin on rifampicin pharmacokinetics in five healthy subjects. Each subject received 600 mg rifampicin with 350 mL of water, and in the second phase, each subject received 600 mg rifampicin plus 500 mg ciprofloxacin with 350 mL of water. In each of the two phases, plasma rifampicin levels were measured from 1 to 24 hours. Treatment with ciprofloxacin significantly increased the half-life and also significantly decreased the maximum peak concentration of rifampicin. Area under the curve time for peak plasma concentration and volume of distribution were not significantly affected. In this study, we found that ciprofloxacin increases the half-life and reduces the maximum concentration of rifampicin in humans.

Effect of activated charcoal on diethylcarbamazine absorption in humans.

We investigated the effect of the oral binder-activated charcoal on the excretion of diethylcarbamazine. Six healthy volunteers were given 150 mg diethylcarbamazine with 350 mL water each. One and 2 weeks later, they received 150 mg diethylcarbamazine plus 7.5 and 15 g activated charcoal, respectively, in 350 mL water as a charcoal slurry. Urinary levels of diethylcarbamazine were measured spectrophotometrically from 1 to 72 hours after ingestion in three different periods. Treatment with activated charcoal led to 5.4% urinary recovery of diethylcarbamazine, decreased excretion rate, and a much lower plateau indicator of reduced absorption. Activated charcoal reduces the absorption and urinary excretion rate of diethylcarbamazine by adsorbing it in the gastrointestinal tract.

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.

Acceleration of body clearance of diethylCarbamazine by oral activated charcoal.

The effect of activated charcoal (AC) on body clearance of diethylcarbamazine (DEC) was investigated in six healthy volunteers. On three occasions at weekly intervals, each subject received 150 mg of DEC with 350 ml of water. One and two weeks later, 150 mg of DEC plus 7.5 g and 15 g of AC, respectively, in 350 ml of water as a charcoal slurry. The non-renal clearance of DEC expressed as the total body clearance of DEC was increased after treatment with AC. The 45.2, 79.6 percent and 58.6, 81.6 percent reductions in maximum concentration and area under the concentration-time curve, respectively, suggest an appreciable adsorption of DEC by AC (7.5 and 15 g) in the gut. Serum eliminating half-life was decreased upon treatment with AC (7.5 and 15 g). These results indicate that AC accelerates the body clearance of DEC by increasing non-renal elimination of the drug.

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.

Effects of pefloxacin on urinary and salivary concentrations of isoniazid in six healthy female volunteers.

The effects of pefloxacin (PFC), a fluoroquinolone antibiotic, on the urinary and salivary concentrations of Isoniazid (INH) were investigated in six healthy female volunteers 19 to 30 years of age. The presence of PFC increased the rate and extent of INH absorption and the rate of its excretion in the urine and saliva. There was an increase in the excretion rate constant (K) and a reduction in the half-life (t1/2) of INH in the presence of PFC. Four of the volunteers had t(1/2) values in the range of 1.55 to 2.43 hours and were considered to be fast acetylators, whereas two subjects with a t(1/2) in the range of 3.36 to 4.41 hours were considered to be slow acetylators. Concurrent administration of INH and PFC may lead to an increased INH toxicity based on the results of the present study.

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.

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.

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.

In vitro adsorption of ciprofloxacin on activated charcoal and Talc.

The in vitro adsorption of ciprofloxacin, a broad-spectrum antimicrobial with actions against a wide variety of microorganisms on activated charcoal (AC) and talc (TC), was investigated at various pH values that simulate the pH of most regions of the gastrointestinal tract. The results of the study indicate that AC and TC adsorbed ciprofloxacin effectively. Adsorption depended on the quantity of the adsorbents used, and for AC adsorption was complete within 2 hours and for TC it was complete within 1 hour with 0.5 g of either of the adsorbents. AC exhibited higher adsorptive capacity for ciprofloxacin than TC. Overall, AC and TC could be used as effective antidotes in poisoning resulting from ciprofloxacin.