Ronald F Donnelly

Physical Compatibility and Chemical Stability of Injectable and Oral Ranitidine Solutions

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.

Stability of Procainamide Injection in Clear Glass Vials and Polyvinyl Chloride Bags

Objectives: The objective of this study was to evaluate the chemical stability of procainamide hydrochloride, 100 mg/mL, when repackaged in clear glass vials or diluted to 3 mg/mL with normal saline and packaged in polyvinyl chloride (PVC) bags when stored at either 23°C and exposed to light (ETL) or 5°C and protected from light (PFL). Methods: Solutions were assayed using a stability-indicating high-performance liquid chromatography method. Samples (5 mL) were collected from triplicate containers on days 0, 7, 14, 21, 28, 56, 91, and 193. Color/clarity and pH changes were also monitored at each time interval. Results: During the study, all samples remained clear and there was only a slight pH change. The color of the solutions stored at 23°C intensified but did not correlate with a significant decrease in concentration, while solutions stored at 5°C remained unchanged. Solutions repackaged in glass vials were stable for 193 days when stored at 23ºC and ETL or 5ºC and PFL. When further diluted to 3 mg/mL with normal saline and packaged in PVC bags, procainamide was also stable for 193 days at either 23ºC and ETL or 5°C and PFL. Conclusions: The stability of procainamide, 100 mg/mL, repackaged in clear glass vials was 193 days when stored at either 23ºC and ETL or 5ºC or PFL. If diluted further to 3 mg/mL with normal saline and packaged in PVC bags, the drug was also stable for 193 days at either 23ºC and ETL or 5°C and PFL.

Stability of Levodopa/Carbidopa Rectal Suspensions

Objective The combination of levodopa and carbidopa (L/C) is used as an effective therapy for treating Parkinsons disease; however when oropharyngeal dysphagia develops or when insertion of an nasogastric tube is not possible, then rectal administration could be used. To reduce compounding workload and establish a beyond use date, this study was conducted to determine the stability of 2 L/C rectal suspension formulations when stored at either 22°C or 5°C. Methods Two formulations of L/C rectal suspension were compounded and then packaged in amber polypropylene bottles. Three bottles of each formulation were stored at either 22°C or 5°C and analyzed at 11 time periods. Physical parameters such as caking, ease of resuspending, and pH were also determined at each time period. A validated stability-indicating high-performance liquid chromatography (HPLC) method was used to analyze both active ingredients. Results All solutions were easy to resuspend, there were no signs of caking, and there was no significant change in pH over the 35 days of storage at either temperature. The glycerin-based formulation (formulation 1) was less stable at 22°C (10 days) than formulation 2 (24 days). Both rectal suspensions were stable for 35 days when stored at 5°C. Conclusions The physical compatibility and chemical stability of 2 formulations of L/C rectal suspension packaged in amber polypropylene bottles was determined to be either 10 or 24 days when stored at 22°C or 35 days at 5°C.