Repackaging of solid oral dosage forms : interest of the evaluation of tablet physical parameters
2 UTCBS UMR CNRS 8258 U1022 INSERM Faculté de Pharmacie- Université Paris Descartes, Sorbonne Paris Cité
Evaluation of the risk of degradation by exposure to relative humidity on repackaged tablets prepared into dose administration aids (DAA) .
Material and Methods
3 drugs were selected (Modopar®125 mg, Depakine®500mg and Esidrex®25 mg) for their sensitivity to moisture demonstrated by the hygroscopicity assay (5.11) of the European Pharmacopoeia. Moisture permeation of two packagings conventionally used in the hospital pharmacy for manual (PERO’S®) or automated (EURAF®) repackaging were tested in accordance with USP <671>. For each dosage form, repackaged tablets were evaluated according to the European Pharmacopoeia tests of hardness (2.9.8), disintegration (2.9.1), friability (2.9.7) and weight variation after 24 hour exposure under 80% ± 2% relative humidity at 23 ° C ± 1 ° C and compared to control unexposed tablets.
In addition, chemical degradation of Esidrex® was assessed by a stability-indicating HPLC method under the same conditions.
Results and Discussion
The moisture permeation of the packagings tested according to USP showed that both, EURAF® and PERO’S® could be qualified as class B with a weight gain > 5mg / day of at most one unit and no unit > 10mg / day. Depakine® tablets showed no changes in physical parameters when exposed to high humidity levels. This can be explained by the enteric coating which can form a protective barrier. Conversely, significant differences p <0.001 vs control (ANOVA Dunnett’s multiple comparison test) were observed for all physical parameters in both packagings for Modopar® tablets, contraindicating their repackaging in the tested packagings. Considering Esidrex® tablets, significant variations in weight, hardness, and disintegration time, were observed mainly in PERO’S packaging, while only disintegration time changed in EURAF® packaging, compared to tablets in control packaging.
In contrast, the chemical stability of hydrochlorothiazide was not affected regardless of the packaging.
Physical tests are useful to highlight different sensitivity of solid dosage forms to moisture in repackaging conditions. Tablets that are significantly affected by exposure to humidiy can hence be easily excluded from repackaging.