Preformulation Study of Controlled-Release Galantamine Matrix Tablets Containing Polyethylene Oxide, Hydroxypropyl Methylcellulose, and Ethylcellulose

<b>Background/Objectives</b>: The rational design of modified-release matrix tablets requires a thorough understanding of granulometric analysis, compaction behavior, and drug release profile. In this study, we evaluated the physicochemical, granulometric, and mechanical properties of hydroxypropyl methylcellulose, polyethylene oxide, and ethylcellulose in galantamine matrix formulations. <b>Methods</b>: Spectroscopic (FTIR) and thermal (DSC) analyses demonstrated drug-polymer compatibility. We assessed flowability, cohesion, and aeration behavior through granulometric analysis and applied compressibility models (Kawakita, Heckel, Leuenberger) to characterize deformation mechanisms. <b>Results</b>: Hydroxypropyl methylcellulose showed superior compactability (T_max = 4.61 MPa) and sustained drug release (85.4% at 12 h, DE% = 62.2%), while polyethylene oxide enabled gradual erosion and consistent delivery (88.7% at 12 h, DE% = 57.5%). In contrast, ethylcellulose exhibited high cohesiveness but poor matrix integrity, leading to premature drug release (76.6% at 1 h, DE% = 73.7%). Only hydroxypropyl methylcellulose and polyethylene oxide formulations met USP criteria. <b>Conclusions</b>: These results demonstrate that polymer selection critically influences powder behavior and matrix performance, underscoring the need for integrated granulometric and mechanical evaluation in the development of robust controlled-release systems.