Beyond-use date of extemporaneous morphine hydrochloride oral solution

C.-Y. Lin
L.-J. Shen
C.-F. Huang
H.-L. Yang
Y.-J. Chen
F.-L.L. Wu

Abstract

Hospital pharmacists prepare morphine oral solution extemporaneously in Taiwan because of the unavailability of commercial products. According to the United States Pharmacopeia 〈795〈, extemporaneous oral solution has an expiration of 14 days if there is no stability test data. However, outpatients usually need 4-week medications. The purpose of this study was to determine the beyond-use date of extemporaneous morphine hydrochloride (HCl) oral solution. Extemporaneous 0.1% morphine HCl oral solutions were prepared in an International Organization for Standardization (ISO) Class 8 compounding room, and bottled in 500-mL high-density polyethylene (HDPE) bottles with polypropylene caps. Twelve bottles were divided into 2 groups (sealed or opened daily) and stored under refrigeration or at room temperature to determine the chemical and microbial stabilities. Stability tests of the "sealed" group were performed after 4 weeks, while for the group in which the bottles were shaken and opened twice daily, stability tests were performed weekly. Chemical stability was determined by high performance liquid chromatography and pH, and microbial stability was determined by microbial limit tests according to pharmacopeias. In both groups, all the morphine HCl oral solutions retained more than 90% of the original concentration after 4 weeks, irrespective of whether they were stored at room temperature or in the refrigerator. The pH values were maintained at around 5 during the 4-week study period. All the refrigerated solutions passed the microbial limit tests within 4 weeks, regardless of whether they were sealed or opened twice daily. All the solutions stored at room temperature retained their microbial stability in the 1st week. However, mold and yeast counts exceeded the limits during the 2nd week in the "opened daily" group. Extemporaneous 0.1% morphine HCl oral solutions prepared in an ISO Class 8 clean room have a beyond-use date of 4 weeks in HDPE bottles when refrigerated. The beyond-use date decreased to 1 week when stored at room temperature. Extrapolation of this result may be limited by different compounding environments, containers or formulations. Copyright © 2013, Food and Drug Administration. Published by Elsevier Taiwan LLC. All rights reserved.

ScienceDirect Link

10.1016/j.jfda.2013.05.002

Recommended Citation

Lin, C.-Y.; Shen, L.-J.; Huang, C.-F.; Yang, H.-L.; Chen, Y.-J.; and Wu, F.-L.L. (2013) "Beyond-use date of extemporaneous morphine hydrochloride oral solution," Journal of Food and Drug Analysis: Vol. 21 : Iss. 2 , Article 14.
Available at: https://doi.org/10.1016/j.jfda.2013.05.002