Characterization of tamoxifen in crosslinked alginate microparticles

Purpose: Physical-chemical characterisation of tamoxifen (TMX) in alginate microparticles for the uptake by Peyer’s patches after oral administration. Methods: Uncrosslinked microparticles were prepared by spray-drying of hydro-alcoholic solutions of alginate/TMX (1:0.1) mixtures. A subsequent crosslinking process by calcium ions and chitosan provides crosslinked microparticles. The obtained microparticles were evaluated for morphology and size by SEM and drug loading level. Tamoxifen physical state inside the microparticles was analysed by DSC and IR analysis. Rheological analysis was performed to detected chemical interaction between the drug and the polysaccharide. Results: Tamoxifen citrate salt exists in two polymorphic forms, metastable form A, stable form B. Commercial product was metastable form A. The microscopic observation of the obtained microparticles revealed a size in 1-3 m range, which is considered proper to be taken up by M cells of Peyer’s patches. Following the spray-drying process, TMX was found in an amorphous state. The rheological analysis, detecting polyelectrolite electroviscous effect, demonstrated the TMX/alginate interaction leading to a suitable drug loading level and to a drug immobilisation within the microparticles. Conclusions: Tamoxifen citrate salt is widely used as the primary hormonal therapy for metastatic estrogen receptor-positive breast cancer. However, side effects include endometrial pathologies, liver cancer and ocular effects. The designed microparticles could be taken up by Peyer’s patches and translocate the drug to the lymphatic system, so avoiding the first-pass metabolism and enzymatic degradation from cytosolic enzymes of the epithelial cells. Therefore, an improved TMX bioavailability could lead to a decrease of the therapeutic dose and, consequently, of the side effects.