How Does Long-Term Storage Influence the Physical Stability and Dissolution of Bicalutamide from Solid Dispersions and Minitablets?

Abstract

The stability of amorphous drugs is among the main challenges in the development of solid dosage forms. This paper examines the effect of storage conditions (25 °C/60% RH and 40 °C/75% RH) and different packaging materials, i.e., polystyrene containers and PVC/Al blisters, on the crystallinity and dissolution characteristics of solid dispersions containing bicalutamide and polyvinylpyrrolidone. The results confirmed drug amorphization upon milling and improved dissolution resulting from the lack of a crystal lattice. These properties varied with time regarding sample composition, storage conditions, and packaging material. The most resistant to storage conditions was the 1:1 solid dispersion packed into blisters. Based on the obtained results, the 1:1 solid dispersion was formulated into minitablets, which were then tested after tableting and then packed into PVC/Al blisters and stored for six months in the same conditions as solid dispersions. We proved that efficient stabilization of amorphous bicalutamide depends on the barrier properties of packaging materials and that a properly chosen material protected the drug substance from the influence of unfavorable storage conditions such as elevated temperature and humidity.