Abstract
Conventional formulations of pirarubicin hydrochloride for injection dissolve rapidly in water for injection and 5 % glucose injection but they are not very soluble in saline. Therefore, medical practitioners in hospitals have desired a new formulation of pirarubicin hydrochloride for injection that dissolves readily in saline. In view of this, we conduced an investigation of solubilizers and found that pirarubicin hydrochloride dissolved rapidly in saline when nicotinamide was added, and developed a formulation of pirarubicin hydrochloride for injection containing 25 mg of nicotinamide per 20 mg potency of pirarubicin hydrochloride.
1H-NMR spectrum analyses revealed that self-association of pirarubicin molecules occurred in saline. The results of such analyses suggested that pirarubicin hydrochloride rapidly dissolved when nicotinamide was added because it inhibited the selfassociation of pirarubicin molecules by preventing interaction between them. As other findings, the chemical stability and in vitro pharmacological effect of the new formulation of pirarubicin hydrochloride for injection as well as its pharmacokinetics in rats were similar to conventional formulations, and nicotinamide did not provide a local stimulus to the rabbit bladder.
