Hyperthermia-induced in situ drug amorphization by superparamagnetic nanoparticles in oral dosage forms

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) generate heat upon exposure to an alternating magnetic field (AMF) which has been studied for hyperthermia treatment and triggered drug release. This study introduces a novel application of magnetic hyperthermia to induce amorphization of a poorly aqueous soluble drug, celecoxib, in situ in tablets for oral administration. In situ amorphization can overcome the drug development hurdle of poor aqueous solubility by molecularly dispersing the drug in a polymeric network inside a tablet. However, current shortcomings of this approach include low drug loading in the tablets, toxicity of enabling excipients, and drug degradation. Here, SPIONs produced by flame spray pyrolysis are compacted with polyvinylpyrolidone and celecoxib, and exposed to an AMF. The degree of amorphization is strongly linked to the maximum tablet temperature achieved during AMF exposure, which depends on SPION composition and content in the tablets. Manganese ferrites exhibit no toxicity in human intestinal Caco-2 cell lines and are more effective than zinc ferrites in inducing complete amorphization of celecoxib. The resulting rapid dissolution and high solubility of in situ amorphized celecoxib in biorelevant intestinal fluid demonstrates the promising capability of SPIONs as enabling excipients to magnetically induce amorphization in situ in oral dosage forms.