Dissociation constants and assay of weak bases in non-aqueous solvents.

A method is described for evaluating standard cell potentials of specific electrode pair systems in anhydrous acetic acid and acetonitrile. The dissociation constants (K(HB+)) in acetonitrile and the overall dissociation constants (K(B)) and (K(BHClO4)) in anhydrous acetic acid of a series of bases of pharmaceutical interest have been determined. Simple potentiometric and visual titration methods are proposed for the assay of bases and their mixtures.

Effect of proteolytic enzymes and polypeptides on the antacid activity of almagate and other antacids.

The acid neutralizing capacity of almagate (hydrated aluminium-magnesium hydroxycarbonate, Al2Mg6(OH)14(CO3)2 X 4H2O, Almax), magaldrate and an aluminium-magnesium hydroxide cogel was measured in the presence of different concentrations of pepsin or peptone. The crystalline antacids, almagate and magaldrate, when tested in the absence of polypeptides were less active acid neutralizing agents than the aluminium-magnesium hydroxide cogel but in the presence of the polypeptides they were considerably more active, especially in respect of time of neutralization. In the presence of pepsin, almagate was considerably more active than in the absence of this enzyme, whereas magaldrate suffered little change in activity and the dried aluminium-magnesium cogel was less active. The results demonstrate the importance of measuring acid neutralizing capacity in presence of naturally occurring polypeptides.

Characterization of a new crystalline synthetic gastric antacid, almagate.

A new crystalline hydrated aluminium-magnesium hydroxycarbonate, almagate (Almax) is described. It has been shown to have an empirical formula Al2 Mg6(OH)14(CO3)2 X 4 H2O X. X-ray diffraction spectra indicate that it is different from other related antacids and that its crystal structure is made up of brucite layers, in which magnesium is replaced by aluminium in the ratio of 3 to 1, interposed with negatively charged layers containing carbonate ions and water. Analysis of the IR spectra suggests that the interstitial carbonate is coordinated to both metals. Differential thermal analysis demonstrates that almagate has good thermal stability and measurement of its antacid activity shows that it has a rapid neutralization velocity and a high acid consuming capacity.

Stability of almagate and pharmaceutical formulations prepared from it.

The stability under accelerated conditions of almagate (Al2Mg6(OH)14(CO3)2 X 4 H2O, Almax) a new crystalline synthetic hydrated aluminium-magnesium hydroxycarbonate antacid, and pharmaceutical formulations prepared from it, were compared with other pharmaceutical formulations prepared from aluminium hydroxide gel or co-gels of aluminium-magnesium hydroxide. The antacid properties of almagate, Almax tablets and suspension, did not change during eight months storage at 60 degrees C whereas preparations of aluminium hydroxide gel and aluminium-magnesium hydroxide co-gel suffered considerable losses in acid neutralization capacity. Neither the X-ray diffraction nor the IR absorption spectrum of almagate changed during storage for 8 months at 60 degrees C. Thus almagate and pharmaceutical formulations prepared from it are thermally stable and will maintain their antacid properties for long periods of time unlike products prepared from aluminium hydroxide gels or aluminium-magnesium hydroxide co-gels.

In vitro comparison of the antacid potencies of almagate in tablets and suspension with those of other commercially available antacid preparations.

Almagate (hydrated aluminium-magnesium hydroxycarbonate, Al2Mg6(OH)14(CO3)2 X 4 H2O, Almax) in the form of tablets and suspension was compared with other commercially available antacid preparations in a battery of tests designed to evaluate antacid activity and related properties. The evaluation of an antacid should take into account, in addition to total acid neutralising capacity, neutralising capacity under dynamic conditions related to in vivo events, bioavailability, speed of action, lack of possible rebound effect and low sodium content. When these considerations are taken into account Almax tablets and suspension can be classified as highly effective antacids retaining a high proportion of their total neutralising capacity under simulated in vivo conditions. As in the case of the active principle, almagate, the enzyme pepsin has a positive effect on acid neutralising activity.

Evaluation of a new antacid, almagate.

Almagate (Al2Mg6(OH)14(CO3)2 X 4 H2O, Almax), a crystalline hydrated aluminium-magnesium hydroxycarbonate, was compared with a number of other known antacids in a battery of tests designed to demonstrate the properties of an ideal antacid. In dynamic tests for measurement of velocity of neutralization, total acid consuming capacity and duration of activity, almagate like other crystalline aluminium magnesium hydroxide derivatives such as hydrotalcite and magaldrate was rapidly acting, neutralized a high proportion of its theoretical acid consumption and maintained gastric pH between 3 and 5 for a prolonged period of time. It was more active than these two substances in respect of rapidity of action and did not lose antacid activity as the pH was raised. Like these compounds it had considerable advantages over the amorphous gels and co-gels of aluminium and magnesium hydroxides or hydroxycarbonates in respect of both rapidity of action and acid consuming capacity. It inhibited the activity of pepsin and was shown to adsorb bile acids and had a low sodium content.

Simultaneous determination of cephalexin and lysine in their salt using high-performance liquid chromatography of derivatives.

A sensitive and useful high-performance liquid chromatographic method using derivatization was developed for the simultaneous determination of intact cephalexin and lysine in their salt. This method is rapid and reliable, and its inherent specificity makes it an improvement over the common wet chemical methods for stability studies.