Kinetics studies of the degradation of sirolimus in solid state and in liquid medium

The use of sirolimus and its analogs has been evaluated for the treatment of different cancer types. The stability studies of sirolimus enabled to determine the kinetics of its chemical reactions in solid state and in the liquid medium. During intrinsic stability tests in a liquid medium, sirolimus showed a lack of stability when exposed to heat, neutral and basic hydrolysis. Analysis by high-performance liquid chromatography detected: two degradation products after exposure to heat; one degradation product for both basic and neutral hydrolyses; and all degradation products exhibited UV spectra similar to the drug’s spectrum. Kinetics studies in a liquid medium revealed low drug stability in methanolic solution; this instability may be exacerbated in the presence of water or high pH. The application of solid-state kinetic models showed that the drug degrades in accordance with the diffusion dimensional model, with greater stability and an expiration date equal to 6 years, demonstrating that sirolimus has satisfactory stability in the solid state. Through this understanding, it is possible to develop more stable pharmaceutical formulations using sirolimus.