Long-term Stability of Zonisamide, Amitriptyline, and Glycopyrrolate in Extemporaneously Prepared Liquid-dosage Forms...

The lack of commercially available liquid dosage forms for pediatric patients prompted this study. The objectives of our study were to determine the stability of zonisamide, amitriptyline, and glycopyrrolate in extemporaneously prepared oral suspensions in plastic prescription bottles. One group of suspensions was prepared in OraPlus:OraSweet (1:1) for each drug and stored either under refrigeration (4°C) or at room temperature (25°C). A second group of suspensions were compounded in 1% methylcellulose:simple syrup at a 1:10 proportion for zonisamide, amitriptyline, and glycopyrrolate; these suspensions were stored at either under refrigeration (4°C) or at room temperature (25°C). The drug concentrations were measured by the stability-indicating high-performance liquid chromatographic methods. The mean concentration of zonisamide (10 mg/mL) remained above 95% of the original concentration for 91 days in each group of suspensions at both 4°C and 25°C. The mean concentration of amitriptyline (20 mg/mL) was above 95% for 91 days in the suspensions containing OraPlus/ OraSweet at both 4°C and 25°C. However, in the suspensions containing methylcellulose:simple syrup, the mean concentration of amitriptyline was about 95% for 42 days at 4°C and 28 days at 25°C. The mean concentration of glycopyrrolate (0.2 mg/mL) was above 95% in each group of suspensions during the 14-day study period. These data indicate that zonisamide, amitriptyline, and glycopyrrolate can be prepared extemporaneously as suspensions and stored in plastic prescription bottles for varying periods at 4°C and 25°C for use in pediatric patients.