Study Evaluates Benefits of Atmosphere Control in Blisters

Table 1: Blistering and storage conditions used for the stability study.

Two different initial relative humidities were modeled to assess how starting water content would impact shelf-life. To confirm the modeling results, tablets were packaged and stored under these conditions for up to 6 months prior to analysis. The companies report:

• Tablets were stressed (open) over a temperature range of 35°C - 60°C and a relative humidity range of 11% RH - 75% RH.
• Related substances were quantified by HPLC and the growth of the main degradant modeled. A good model was obtained with activation energy (i.e. temperature sensitivity) and moisture sensitivity values in the average range for similar products.

PCI performed the blister packaging for the two categories: (1) low RH, where tablets were stored in the presence of silica gel desiccant until blistering and (2) high RH, where tablets were placed in a 25°C/60% RH stability chamber for 24 hours before blistering.

Blistered tablets were stored in reach-in stability chambers (Darwin PH030) at FreeThink Technologies.

Key takeaways

As the ASAP study had predicted, the packaging configurations were ranked in the following way from most protective against degradation to least protective of the model tablet:

• Activ-Blister technology with molecular sieve
• Activ-Blister technology with silica gel
• Coldform foil
• Thermoform blister alone

Figure 1 shows growth of the main degradant in tablets stored under various conditions.

Figure 1: Probability of passing with a 2-yr shelf life at 25°C/60% RH, 30% dosage RH: Molecular sieve: 99%, Silica gel: 95%, Cold-form foil: 71%, Thermoform alone: 24%. Activ-Blister™ with molecular sieve results in the lowest degradant growth. The impact of Activ-Blister™ packaging configurations is highest with high dosage RH (60% RH).The advantage of Activ-Blister solutions over cold-form foil was particularly pronounced when the drug product had a high initial water content. Active packaging technologies may help manufacturers with moisture-sensitive drugs benefit from the commonly used thermoform blister.

The ASAPprime program was found to be effective at modeling packaging configurations incorporating molecular sieve and silica gel versions of Activ-Blister (Figure 2).

 Figure 2: Selected ASAPprime predictions compared to degradant growth in tablets stored under ICH stability conditions. The blue lines show the mean prediction while green and red lines show the 95% confidence interval. The 40°C/75% RH conditions have differing scales due to the wide range of degradation.