Quantitative evaluation of release behavior of synthetic taste-masking drugs using polysaccharide-based carrier with direct analysis in real-time mass spectrometry

Sodium alginate (ALG) is widely used as a taste-masking excipient in pediatric oral formulations, yet its release behavior is strongly governed by molecular structure. azithromycin (AZM, targeted bitterness probes)-loaded ALG microspheres using five different ALG specifications (with various molecular weights or mannuronic-to-guluronic acid (M/G) ratios) were prepared, with loading efficiencies between 17.71–19.48%. Thereafter, an on-line release-evaluation method was developed by integrating a flow-pump dissolution model with direct analysis in real time mass spectrometry (DART-MS), enabling dynamic monitoring of AZM release under simulated oral conditions. Consequently, both molecular weights and M/G ratios were verified that can significantly affect the release behavior of the microspheres. Microspheres prepared by ALG with lower M/G ratios showed consistently limited release across the 1200-s testing period, reaching approximately 3% cumulative release. In contrast, those derived from ALG with higher M/G ratios displayed faster initial release during 0–300 s and achieved approximately 12% cumulative release at 1200 s. Molecular weight further modulated late-stage release, with lower-molecular-weight ALG samples exhibiting more significant increases in total AZM release. This approach offers a quantitative and mechanism-supported framework for optimizing polysaccharide-based taste-masking systems and achieving controlled drug release in pediatric formulations.