Instability kinetic evaluation of methotrexate in physiologic pH and temperature condition

Abstract

Today, it's become established that methotrexate (MTX) has good efficacy for the treatment of various disease such as leukemia or rheumatoid arthritis and so on. Although high-dose MTX is easily prescribed for most patients, it can cause severe toxicity including nephrotoxicity. Clearance of the drug from the body following this complication can be delayed. Therefore, it is more desirable to use controlled drug delivery systems for dose reduction and systemic toxicity and drug delivery for a long time. In addition to the above, the chemical instability of the active molecule can lead to a significant reduction in the amount of drug in physiologic conditions. Therefore, it is important to know the nature of the methotrexate reaction at physiological pH and temperature. Considering this, we use phosphate-buffered saline with physiologic pH for release of MTX. As our study showed, methotrexate molecules present instability during the physiological conditions for 48 hours. The present study helps in considering studies of methotrexate taking into account the critical factor of instability, considering the calculated rate constant.