Impact of additives on the long-term physical stability of antidepressant citalopram hydrobromide in personalized drug delivery systems.

This study aimed to investigate the effect of the manufacturing process, composition, and storage on the long-term physical stability of antidepressant citalopram hydrobromide (CHB) in oral solid foams as personalized drug delivery systems. Hydroxypropyl methylcellulose (HPMC) was used as the polymer matrix former, whereas glycerol and polysorbate 20 as liquid starting materials, and poly(ethylene oxide) 4000 (PEO 4000) and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) as solid starting materials were used as additives to improve mechanical, wetting and/or disintegration properties of solid foams. CHB-containing transparent HPMC-based gels with and without additives were freeze-dried, and the well-formed and sturdy solid foams were stored under different storage conditions for three years. Solid foams were analyzed for solid-state, morphological, mechanical, disintegration, and drug release properties. Crystalline starting materials CHB, PEO 4000 and PEO-PPO-PEO were amorphous after freeze-drying in the freshly prepared foams. The solid form of CHB and additives were affected by storage conditions and the amount of additives. CHB remained amorphous when additive-free and glycerol and polysorbate 20-containing solid foams were stored in a dry environment for three years. In other storage conditions, the higher the amount of additives, the faster the onset of CHB recrystallization was. The solid foams remained mechanically resistant, independent of storage conditions, though foams became thinner in the accelerated storage conditions. Additive-containing freshly prepared foams released CHB faster than additive-free foams. The difference in the release profiles of CHB from these foams became insignificant on storage. These findings indicate that CHB-loaded solid foams should be stored in a cold and dry environment, or the formulation without additives should be used to ensure the long-term physical stability of ingredients in the foam.