Determining a use-by date (UBD) on repackaged administration doses

Objectives
An administration dose is an appropriate packaging of a unit of medication in a single-dose container, intended for administration to the patient. Each unit dose must bear various legal indications, such as the active substance, dosage, batch number and expiration date. While in France there is no precise definition or legal text on the preparation of doses to be administered (PDA), apart from a mention in article R4235-48 of the public health code, in Belgium, the Royal Decree of September 30, 2020 qualifies the unit dose as a pharmaceutical preparation to be carried out in accordance with PIC/S PE 010-4 standards. The aim of this work is therefore to determine a UBD for doses to be administered after (re)packaging.

Methods
As no recommendations are described in the European Pharmacopoeia (Ph. Eur.), the determination of the UBD of the doses to be administered was carried out using the "<671> Containers - Performance Testing" test of the United States Pharmacopoeia (USP). This text was adapted so that the test could be carried out in all hospital pharmacies with simple means. The method involved the use of 3 types of substance : deliquescent (CaCl2), hygroscopic (Na2HPO4) and slightly hygroscopic (microcrystalline cellulose). The experiment involved PDA according to the pharmaceutical art and weekly weighing of each unit. Storage took place in real conditions, i.e. without humidity and temperature control.

Results
The increase in unit mass over time is associated with the absorption of moisture by the substance through its packaging. Packaging is classified as "low barrier" if mass uptake is ≥ 1 mg/day and "high barrier" if it is < 1 mg/day. The mass uptake of CaCl2 units packaged in PVC/PVdC/aluminium blisters produced by Pentapack^® equipment was 0.2209 mg/day over 6 months, compared with 0.0170 mg/day and 0.0136 mg/day respectively for Na2HPO4 and microcrystalline cellulose units weighed over 3 months. The mass intake of CaCl2 units packaged in manual Medidose^® PVC, aluminum and paper blisters was 2.7262 mg/day, qualifying this packaging as "low-barrier".

Discussion/Conclusion
The results of the moisture permeability test are best with Pentapack^® packaging, which maintains the "high barrier" for 6 months. Thus, if these results are maintained for 24 months, the expiry date of doses to be administered packaged using Pentapack^® equipment could be 2 years for hygroscopic substances. The results obtained with Medidose® blisters, on the other hand, limit their use, and impose an expiry date of no more than 1 month.

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