A client came to FreeThink with the challenge of having a capsule drug product with a three-year shelf-life in foil-foil (alu-alu), cold-form blister in Zone II (25°C/60%RH). the client wanted to provide this critical medication to sub-Saharan Africa (Zone Ivb, 30°C/75%RH), and find a cost-effective packaging option to meet this need.
This product was sufficiently old that the shelf-life was determined by loss of potency (assay) on storage. FreeThink worked with the client to establish release and stability specifications (95-105% and 90-110%, respectively). Our scientists designed and carried out an ASAPprime® study on the capsules. Based on the formulation, FreeThink was able to determine the moisture sorption isotherm of the product.
The product was found to have both a high temperature sensitivity (Ea = 42.5 kcal/mol) and moisture sensitivity (B = 0.101). This means that as previously produced in foil-foil blisters, the product showed >95% probability of passing at 25°C/60%RH in the labeled three-year period. When this same product was brought to Zone IVb (30°C/75%RH), this probability decreased to 71%. To get to a 95% probability of passing, the dating with this packaging would need to be reduced to 15 months.
With its high moisture sensitivity, this product is stabilized rapidly with reduced RH. With the product being in gelatin capsules, reducing moisture is difficult without making the capsules brittle. At FreeThink, we showed that using HPMC capsules did not impact the product stability, yet prevented cracking at low RH conditions. Using these HPMC capsules, we can achieve >95% probability of passing by packaging in bottles (30 capsules in 60-cc HDPE bottles with HIS) using 2 g of silica gel desiccant.