Solubility problems in formulation Shtore XV Sulfamethoxazole pKa 603

solution sulfamethoxazole and trimethoprim demonstrate a high degree of incompatibility and mutual precipitation occurs on mixing. To optimise mutual dissolution, an aqueous solution which includes 40% propylene glycol is utilised in the formulation of the infusion. This solution, which has a pH between 9.5 and 11.0, allows adequate amounts of both substances to coexist in solution to give the correct ratio of concentration for antibacterial action. On dilution, the infusion becomes less

5.7.1 Mixtures of acidic and basic compounds

Sometimes a combination formulation requires the admixture of acidic and basic drugs. One example (Septrin infusion) is discussed here.

Because sulfamethoxazole (XVII) is a weakly acidic substance and trimethoprim (XVIII) is a weakly basic one, for optimal solubility basic and acidic solutions, respectively, are required. In consequence, in an ordinary aqueous

Structure XVIII Trimethoprim, pKa = 7.05

stable and at the recommended 1 in 25 dilution stability is about 7 hours. Owing to incompatibility of the two constituents, their degrees of solubility are sensitive to changes in ionic composition, pH and any drug additives. If there is imbalance in pH or ionic composition, then precipitation of one or other of the components may well occur.

5.7.2 Choice of drug salt to optimise solubility

The choice of a particular salt of a drug for use in formulations may depend on several factors. The solubility of the drug in aqueous media may be markedly dependent on the salt form. The chemical stability rather than the solubility may be a criterion and in many cases this is dependent on the choice of salt, sometimes through a pH effect. Deliberate choice of an insoluble form for use in suspen-

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