Ampicillin adsorption by some antacids

In certain situations of peptic ulcers ampicillin has been co-administered with bismuth carbonate with an implication for adsorption of the ampicillin. To quantify this effect the kinetics and extent of adsorption of ampicillin by some commonly used antacids were measured; these are bismuth carbonate, magnesium trisilicate and aluminium hydroxide. The adsorption of ampicillin by bismuth carbonate followed the Langmuir adsorption isotherm, which suggests chemisorptions. It was characterized by a strong adsorption at a low adsorbate (ampicillin) concentration but the % adsorption decreased with increase in adsorbate concentration, which is a feature of a saturated monolayer adsorption. On the other hand, the adsorption by magnesium trisilicate and aluminium hydroxide followed the Freundlich adsorption isotherm characterized by a low adsorption at a low adsobate concentration but this increased slightly with increase in adsorbate concentration, suggesting a weak physical adsorption. The adsorption capacities (mglg) of the adsorbate were 1.64 (bismuth carbonate) 0.04 (magnesium carbonate) and 0.03 (aluminium hydroxide). Bismuth carbonate thus gave by far the highest degree of adsorption. The conclusion is that the co-administration of ampicillin and bismuth carbonate in the treatment of certain peptic ulcers is erroneous.


Introduction
Antacids and anti diarrhoeas are potent adsorbents and consequently they impair the bioavailability of concomitantly administered drugs.For instance, the adsorption of promazine by antalpugite [I], lincomycin by various anti-diarrhoea preparations [2], and the quinolonebased antibiotic (ofloxacin) due to chelation (i.e.chemisorption) by the metallic antacids (sodium bicarbonate, magnesium trisilicate, and aluminium hydroxide) [3] have been reported by various authors.Now, ampicillin and bismuth carbonate have been used as combination therapy in the management of certain peptic ulcers complicating Hellicobacter infection.The objective of this study therefore is to investigate whether the antacid powders appreciably adsorb ampicillin and if so, to investigate the mechanism of adsorption.Besides, reports of ampicillin adsorption by antacids are rare in the literatures; hence this study was undertaken.

Materials and methods
Ampicillin trihydrate (a product of Sigma, U.S.A.) was the test drug.It is sparingly soluble in water dissolving one part in 150 parts of water (i.e. about 7mglml) at 20°C.Hence its adsorption, may markedly affect its bioavailability.The test antacid powders were aluminium hydroxide, bismuth carbonate and magnesium trisilicate; all analar grade and received from Halewood chemicals Ltd.Middlesex, London.Their mean particle sizes as determined by photomicroscope were in the range 0.5 -5 5 0.002pm.

Adsorption studies
Aqueous solutions of ampicillin trihydrate in water (0.5mglml -4.5mgIml) were prepared.A sample of the antacid powder (Ig) was added to 10ml aliquots of the ampicillin solutions and the mixtures shaken 100 rev.min-' at 37°C for 1 h in a shaker bath.The mixtures were centrifuged at 300 rev.min for 30 min after which the supernatants were analysed for content of residual ampicillin.The difference between initial amount of ampicillin and the equilibrium content was taken as the ampicillin that was adsorbed; this was expressed as a percentage of the initial amount of ampicillin in solutions.The adsorption capacity was expressed as the milligram of ampicillin adsorbed per gram of the adsorbent.

Analysis of arnpicilin
Content of ampicillin in the supernatants was analysed by spectrophotometric methods [4].A supernatant derived from a suspension of the antacid powder in water (without ampicillin) was used as control in the analysis.In the procedure 0.2 ml supernatant was made up to 10ml with phosphate buffer (pH, 5.5) containing copper ions, 15pglml.The samples were heated at 75C0 for 30 mins to hydrolyse the ampicillin to penicillanic acid, which was the moiety that was determined spectrophotometrically at A , , , 320 nm.The determination was carried out in triplicate and mean results calculated.

Adsorptive potentials of the antacids
The extent of adsorption at the various adsorbate concentrations is given in table 1.It can be seen that with bismuth carbonate the adsorption was strong (upto 52% of the initial amount of adsorbate) at the low adsorbate concentration, O.5mglml but this decreased to 13% at the higher adsorbate concentration, 4.5mglml.The adsorption reached a plateau at the adsorbate concentration, 2mglml.These results suggest a saturation of the adsorptive surface area.With the other two adsorbents (aluminium hydroxide and magnesium trisilicate) the extent of adsorption was weak at the low adsorbate concentration, for instance there was no measurable adsorption at the adsorbate concentration, O.5mglmlI but the adsorption increased slightly as the adsorbate concentration increased and 20% (magnesium up to a maximum of 15% allumimum hydrate).These results suggest that the adsorptive surface area was not readily saturated, as was the case with bismuth carbonate.

Mechanism of adsorption
In order to investigate the adsorption mechanism (i.e. the adsorption isotherm) the data in table 1 were analysed according to the Freundlich and the Langmuir isotherms, which describe adsorption from dilute solutions [5].The Freundlich isotherm is given by where x is the amount of adsorbate adsorbed by an adsorbent of mass, m, C is the equilibrium concentration of the adsorbate.K and n are constants, which for a given adsorbate are measures of the adsorptive capacity of the adsorbent, and the adsorbateadsorbent affinity respectively.In systems obeying the Freundlich These results show that aluminium hydroxide and magnesium trisilicate conformed with Freundlich adsorption while bismuth carbonate deviated.However when the data for bismuth carbonate were analysed for low adsorbate concentrations only (0.5mglml -2mglml) bismuth carbonate now conformed with Freundlich adsorption with a correlation coefficient, 0.966.The values of K and n were thus obtained at this low adsorbate concentration only.

Ampicillin adsorption by some antacids
The Langmuir adsorption isotherm is given by [5]: where a and b are constants for a given adsorbentadsorbate system.In systems obeying the Langmuir isotherm a plot of C. m/x vs C is linear with a slope = l / b and a Yintercept = l/ab.The linear correlation coefficients by this Langmuir analysis for the three adsorbents were 0.9705 (bismuth carbonate), 0.81 52 (aluminium hydroxide) and 0.6273 (magnesium trisilicate), thus indicating that only bismuth carbonate conformed to the Langmuir adsorption isotherm.

Adsorption capacity of the adsorbents and their affinity for the adsorbate
The adsorption capacity (K) of the adsorbents and their affinity (n) for the adsorbate were obtained from the Freundlich isotherm (equation 1).The K values (mg/g) were as follows: 1.64 (bismuth carbonate) 0.04 (magnesium trisilicate), and 0.03 (aluminium hydroxide).The K value is a measure of the extent of adsorption as adsorbate concentration tends to zero bismuth carbonate displayed a stronger adsorptive capacity compared with the other two adsorbents.The affinity index values were 2.5 (bismuth carbonate), 0.66 (aluminium hydroxide), and 0.62 (magnesium trisilicate); which also means that bismuth carbonate displayed the strongest affinity for the adsorbate.Differences in the specific surface area of a powder may influence the extent of adsorption.However, as noted above the particle size distribution in the absorbent powders were not markedly different.Hence the difference in adsorptive capacity relates more to the difference in the adsorption mechanisms rather than particle size differences.

Conclusion
The study has shown that bismuth carbonate adsorbs ampicillin strongly.This finding has important implication in the co-administration of these two drugs in the treatment of certain peptic ulcers.The bioavailability of the ampicillin would be impaired; hence, the practice is erroneous.

1
isotherm a plot of log vs logC is linear with a slope = -and a Yintercept = Log m n K.In the analysis the correlation coefficients for linear regression were calculated.A coefficient close to unity (i.e. 2 0.90) indicates conformity with the isotherm.The values of the correlation coefficients for the various adsorbents were as follows: 0.980 (aluminium hydroxide), 946 (magnesium trisilicate), and 0.749 (bismuth carbonate).

Table 1 :
Amount of ampicillin adsorbed by the various antacid powders C03 functional group of bismuth carbonate.The decrease in percentage adsorption with increase in initial concentration of ampicillin is an evidence for monolayer saturation.On the other hand the weak adsorption of ampicillin by the other two adsorbents is attributable to a physical adsorption mechanism possibly involving multilayer adsorption, which explains the increase in the percentage adsorption with increase in initial concentration of adsorbate (table1).