Stability of hydralazine hydrochloride syrup compounded from tablets

Area of Science:

• Pharmaceutical Sciences
• Drug Stability Studies
• Formulation Development

Background:

• Hydralazine hydrochloride is an antihypertensive drug.
• Developing stable oral liquid formulations is crucial for patient compliance.
• Understanding drug degradation pathways is essential for shelf-life determination.

Purpose of the Study:

• To evaluate the stability of hydralazine hydrochloride in an oral syrup formulation.
• To assess the impact of common pharmaceutical adjuvants on hydralazine hydrochloride stability.
• To determine the shelf life of the hydralazine hydrochloride syrup.

Main Methods:

• Prepared a maltitol-based hydralazine hydrochloride syrup (1.25 mg/mL).
• Stored syrup samples at various temperatures (5-70°C) and analyzed drug concentration using HPLC.
• Tested hydralazine hydrochloride solutions (1%) with different adjuvants (edetate disodium, edetate sodium, sodium bisulfite) at 50°C for one week.

Main Results:

• Hydralazine hydrochloride exhibited first-order degradation across all tested temperatures.
• An Arrhenius plot predicted a syrup shelf life of 5.13 days at 25°C.
• Edetate sodium caused 29% drug loss in one week, while sodium bisulfite led to 80% loss and intense yellowing.

Conclusions:

• Hydralazine hydrochloride is relatively unstable in the developed oral syrup formulation at room temperature.
• Certain adjuvants, particularly sodium bisulfite and edetate sodium, significantly accelerate hydralazine hydrochloride degradation.
• Further formulation optimization is required to enhance the stability of hydralazine hydrochloride in liquid dosage forms.