Characteristics of Tylvalosin Tartrate Enteric Amorphous Pellets Prepared by Liquid Layering

Tylvalosin Tartrate (TAT), a new-generation macrolide antibiotic, undergoes significant degradation in the stomach and in vivo rapid elimination upon oral administration, resulting in poor bioavailability. This study developed TAT enteric amorphous pellets by liquid layering (TAT/EAP-LL) with pH-sensitive and burst release characteristics, to enhance drug stability in the stomach and concentration enrichment in the duodenum.

The drug loading layer, isolation layer and enteric layer were formed on the surface of the blank core pellets. Investigation into the characteristics of TAT/EAP-LL revealed that stable amorphous solid dispersions in the drug loading layer were formed by liquid layering. Then, DSC analysis confirmed that triethyl citrate significantly improved the film-forming properties of Methacrylic-ethyl acrylate copolymer. Additionally, TAT/EAP-LL was confirmed to exist in the amorphous state by DSC、PXRD and PLM.

In vitro, TAT/EAP-LL demonstrated a similar 4.07% release within 2 h at pH 1.0 as TAT enteric pellets (TAT/EP-LL) and a much faster burst release at pH 6.8, with complete release within 15 min. In vivo, the oral bioavailability of TAT/EAP-LL was improved to 1.71 times compared to commercial formulations and 1.47 times compared to TAT/EP-LL.

This study offers a novel platform for the enhanced oral delivery of TAT and proposes effective formulation strategies for pulsatile drug delivery.