Evaluating the Stability of Commonly Prescribed Medicines in Compliance Aids

Abstract

Older people are increasingly using multiple drugs to manage their comorbid diseases, and multicompartment compliance aids (MCAs) – storing devices designed to help patients manage their medication efficiently – are becoming more prevalent. However, the repackaging process involves removing drugs from their original packaging and placing them in containers, which could invalidate the drugs’ integrity. Despite the widespread use of such devices in the United Kingdom, there is a dearth of literature available regarding the stability of repackaged medication. To establish practical guidelines for safe storage and proper handling of refilled drugs, this study investigates the physicochemical stability of the drugs most commonly used by elderly. Three drugs, namely omeprazole, furosemide, and ramipril, were tested over a 28-day period. A multifactorial approach was used to store the drugs under the following five conditions: (1) by a window exposed to sunlight, (2) on a bench exposed to fluorescent light, (3) in a fridge (2–8 °C), (4) in an accelerated condition (40 °C; 75% relative humidity/RH), and (5)in an ambient condition (25 °C; 60% RH). For each condition, the drugs were stored in three ways: in the original packaging, individually in a compliance aid (MCA1), and mixed together in the same chamber (MCA2). All medications were evaluated for their content uniformity using an ultraviolet assay appearance, weight, diameter, thickness/length, and moisture content as per British Pharmacopoeia specifications throughout the 4-week period. All samples, including a control sample, were compared. An analysis of variance revealed a significant decrease (ANOVA, p-value < 0.05) in repackaged omeprazole content when exposed to sunlight. This decrease was more severe under the accelerated condition, where the content markedly declined in both the original packaging and the MCAs; the drug’s colour changed to mauve, and the outer shells of the drugs started to shrink (ANOVA, p-value <0.0001) in both MCA1 and MCA2 starting from day 14. Furosemide’s photochemical instability was confirmed via significant decomposition following exposure to fluorescent light and sunlight; a yellow colour was detected in repackaged furosemide (i.e. MCA1,2) tablets under both lights and in the originally packaged drug under sunlight. The only notable change to ramipril was in the colour of the capsule, which turned light blue when stored in MCA1 and MCA2 under accelerated conditions. Regardless of the previous analysis, all repackaged drugs – except for omeprazole under the accelerated and sunlight conditions – met compendial requirements for a 28-day storage period. In conclusion, although the only drug that failed to meet the pharmacopeia criteria was omeprazole stored in an MCA, discolouration of furosemide (under fluorescent and sunlight) and ramipril (under the accelerated condition) was considered unacceptable. Therefore, if any of the three drugs are to be repackaged in an MCA, patients must be advised to store them in a dark, dry, cool place. Overall, the original packaging provided better protection, and medication segregation was not a significant factor. Further research is needed to enrich the data available on the performance of medication packed in MCAs.