Physical Compatibility and Chemical Stability of Injectable and Oral Ranitidine Solutions

Abstract

Objectives: The physical compatibility and chemical stability of ranitidine hydrochloride injectable solutions and oral syrup were studied to define beyond-use dates (BUDs). Methods: Ranitidine hydrochloride injectable solutions of 25 mg/mL packaged in glass vials and 5 mg/mL in polypropylene (PP) syringes were prepared in triplicate. Samples were refrigerated and protected from light (PFL) or stored at 25°C and either exposed to light (ETL) or PFL. Ranitidine hydrochloride oral syrup 15 mg/mL in unit-dose amber PP syringes were prepared in triplicate and then kept at 25°C. Samples were collected at days 0, 7, 14, 28, 56, and 91. Additional samples were collected at 6 months and at 6, 9, and 12 months for the 25 mg/mL solution and oral syrup, respectively. Physical parameters of pH, clarity, and color were obtained at each collection time. A validated stability-indicating high-performance liquid chromatography (HPLC) method was used to determine the chemical stability. Results: Formulations had no significant change in pH or clarity. Although some samples yellowed, this was not associated with a decrease in concentration. The 25 mg/mL solution remained above 98.6% for 6 months, whereas the 5 mg/mL solution remained above 93.5% for 91 days under all storage conditions. At 25°C, the oral syrup retained greater than 98.8% for 12 months. Conclusions: The ranitidine hydrochloride injectable solutions were stable for 6 months and 91 days under the 3 storage conditions, respectively, for the 25 mg/mL solution in glass vials and 5 mg/mL solution in PP syringes. The 15 mg/mL oral syrup in unit-dose amber PP syringes was stable for 12 months at 25°C and PFL.