Saleh A.H. Khalil

Effect of antacids on oral absorption of rifampicin

Abstract A study has been carried out on the effect of concomitant administration of aluminium hydroxide gel (15 ml), magnesium trisilicate (2 g) and sodium bicarbonate (2 g) on the bioavailability of rifampicin in healthy male volunteers. The antibiotic bioavailability, as measured by a urinary excretion method over a period of 24 h, was significantly reduced by the 3 antacids following the sequence: magnesium trisilicate > aluminium hydroxide > sodium bicarbonate. Doubling the dose of either magnesium trisilicate or aluminium hydroxide gel produced no further reduction. The results obtained are interpreted in the light of the effect of gastric pH elevation on the solubility and dissolution rate of rifampicin, chelation of the drug with aluminium ions and binding by magnesium trisilicate.

Stability and Dissolution Rates of Corticosteroids in Polyethylene Glycol Solid Dispersions

AbstractA study has been made to examine the stability and dissolution rates of prednisolone, prednisone and hydrocortisone formulated as solid dispersions in polyethylene glycols. Of the five PEG samples used, three enhanced the chemical instability of the steroids; the effect being dependent on the PEG sample and storage conditions of the solid dispersions. Dissolution rates of the steroids were relatively fast from the solid dispersions and showed no significant changes upon storage. Using two methods of analysis (direct UV spectrophotometry and the USP blue tetrazolium method), it is concluded that the chemical instability of the steroids in some PEG samples was due to alterations in the dihydroxy acetone side chain. One of the decomposition products found appeared to be an acidic compound resulting from oxidation of the C17 side chain. The oxidation is presumably accelerated by a peroxide impurity in PEG samples.

The uptake of ampicillin and amoxycillin by some adsorbents

Abstract The in vitro uptake of ampicillin and amoxycillin by attapulgite, magnesium trisilicate, veegum and 3 types of kaolin has been studied. Adsorption data were obtained under conditions simulating in vivo with respect to changes in pH values, and the presence of electrolytes, a viscosity-imparting agent and a surfactant. Under all the conditions examined, amoxycillin was much less adsorbed than ampicillin. Desorption experiments at 37°C and pH values 2.0 and 6.5 showed only partial release of the adsorbed antibiotics; the maximum percentage was about 37 after 4 h. The presence of either veegum (l g) or kaolin (4 g) in the dissolution medium (900 ml) did not significantly alter the level of ampicillin or amoxycillin in solution during dissolution testing of the capsule. The data obtained emphasize the importance of investigating in vitro adsorption of drugs under conditions simulating in vivo.

In vitro release of aspirin from various wax‐coated formulations

These disadvantages have been remedied. Although a solution of 5% 4-dimethylaminobenzaldehyde in hydrochloric acid : ethanol (1 :1) turns from yellow to brown within a week, replacement of ethanol by methanol provides a solution which is stable for several months. The use of a porcelain tile or tube is avoided by placing a small amount of the suspect material on a filter paper and adding a drop of the reagent. By chromatographic action the material responding to the reagent is carried away from the bulk of the sample, where dyestuffs and other materials interfere, and is concentrated into striations. It is possible to obtain a response with weak samples of lysergide which have failed to produce a fluorescence with an ultraviolet lamp. The Table summarizes the responses obtained using this technique for some known hallucinogens and structurally related substances. Although similar colour reactions are observed with hallucinogens derived from lysergic acid and the tryptamines, as well as the natural ergot bases and dihydroergotamine, the test is convenient for non-scientific personnel and is much more restrictive than the observation of ultraviolet-induced fluorescence. When taken with adequate circumstantial evidence there is less likelihood of mistakingly seeking professional confirmation. The filter paper may be retained as a record of the test and can be signed and witnessed. A combination of the two techniques assists the examination of heterogeneous specimens. Radial striations of colour develop from the centre of the spot.

The In-Vitro Uptake of a Low Dose Drug (Riboflavine) by Some Adsorbents

AbstractAn investigation was carried out of the in-vitro adsorption of a low-dose model drug (riboflavine) by three typzs of kaolin, attapulgite, magnesium trisilicate and a grade of magnesium aluminium silicate (veegumR. The adsorption experiments were designed under conditions simulating in-vivo with respect to variations in pH values, volume of the adsorption medium, and the presence of electrolytes, a hydrophilic colloid and a surfactant. Under all conditions examined, riboflavine adsorption followed the sequence veegum attapulgite kaolin magnesium trisilicateThe presence of either veegumR (1 g) or kaolin (4 g) in the medium reduced the level of drug in solution during dissolution rate testing of capsules. Desorption results suggest only partial release of the adsorbed drug. The results obtained emphasiz,e the strong uptake of a potent ionic drug by the various silicates commonly used in pharmacy.

Effect of Attapulgite on the Bioavailability of a Model Low Dose Drug (Riboflavine) in Humans

AbstractIn human volunteers, both the rate and extent of urinary excretion of riboflavine were significantly reduced (p<0.05) when attapulgite was co-administered with the drug. About 50% reduction occurred in the cumulative amount excreted following the concurrent administration of 10 mg riboflavine in solution form and 2 g of regular attapulgite. The co-administration of the drug with a 30 ml dose of a commercial antidiarrheal suspension containing 10% activated attapulgite and 3% colloidal attapulgite produced a relatively lesser effect; the reduction in extent of absorption being 40%. No statistically-significant effect was found when the adsorbent was ingested 2 h prior to the drug. The observed reduction in drug bioavailability in the presence of attqapulgite to the significant uptake of the drug by the adsorbent.

Interaction of caffeine with phenothiazine derivatives

Abstract The effect of caffeine on the partition coefficient, permeation across silastic membrane and surface activity of some phenothiazine derivatives was investigated. A decrease in the apparent iso-octane/pH 6.0 partition coefficients, permeation rate constants and surface activity of phenothiazines was indicative of a caffeine-phenothiazine interaction reducing the hydrophobicity of these drugs. Further, such an interaction was shown to decrease the activity of phenothiazines in two simple biological systems, namely haemolysis of erythrocytes and toxicity in fish. This might have some implications for the co-administration of caffeine or caffeine-containing beverages by patients on phenothiazine therapy.

Dissolution rate studies using the B.P. disintegration apparatus.

The application of the B.P. disintegration apparatus in dissolution rate studies has been examined. The dissolution profiles of some brands of chloramphenicol capsules and tolbutamide tablets have been examined at various tube speeds with and without the guided disc. For both drugs a tube speed of 20 strokes/min gave the optimum difference in dissolution rates. The effect of the guided disc depended on the disintegration time of the product tested. For poorly disintegrating products the use of the guided disc resulted in about twofold increase in dissolution whilst insignificant effect was found for products with fast dissolution rate.

A note on the assay of atropine sulphate injections

During a study on the stability of some batches of atropine sulphate injections, the U.S.P. XVII and B.P. 68 methods of assay were compared. Samples of three commercial batches of atropine sulphate injections (U.S.P. XVII), having pH values between 5.2 and 6.0, were subjected to autoclaving for 1 to 6 h. These injections were then assayed by the two methods (Table 1). The B.P. method gave, for all the samples examined, higher results compared with the U.S.P. method. Batch C, which showed by the U.S.P. method about 50% decomposition, gave about 36% decomposition by the B.P. method (Table 1). This particular batch revealed, on using a thin-layer chromatography system, * two spots corresponding to atropine and tropine; the former gave an orange colour and the latter a deep violet colour with dilute potassium iodobismuthate solution. It was concluded, therefore, that the hydrolytic product tropine may interfere in the B.P. method. Tropine, chromatographically pure, was analysed following the U.S.P. and B.P. methods of assay of atropine sulphate injections. The results (Table 2) showed that tropine interferes in the B.P. method; the plot is linear and has a slope of 1-52 indicating the constant contribution due to tropine. The latter in a concentration of 20.3 mg% (corresponding to 100% hydrolysis of atropine sulphate) gave by the B.P. method the equivalent of 30.6 mg% of atropine sulphate. In the U.S.P. method, however, the effect due to

Variations in dissolution rates of sugar-coated chlorpromazine tablets

Abstract The dissolution rates of 14 batches of sugar-coated chlorpromazine tablets (10, 25 and 100 mg) were examined by the U.S.P. method. Although all the batches passed the U.S.P. disintegration test in 0.1 N HCl, none passed the U.S.P. dissolution limit (not less than 80% dissolution after 30 min). Poor dissolution rates were ascribed to delayed break-up of the sugar-coat. The dissolution and dialysis rates of tablets of one batch were dependent on the medium composition suggesting possible drug- excipient interaction.