Abstract There has been great interest in microgels as drug carriers within the pharmaceutical industry. This includes the use of amphiphilic drugs for treating conditions such as depression, allergies, and cancer. By loading adiphenine (ADP), pavatrine (PVT), and diphenhydramine (DPH) into macrogels and observing the release, this study seeks to investigate how amphiphilic drugs can be released from microgels. There is also an interest in how aggregation behavior may vary depending on the structural components. This study utilized small angle x-ray scattering (SAXS) along with UV analysis and the measuring of the binding isotherm to investigate micelle aggregation and aggregation number. Two of the drugs adiphenine and pavatrine, have similar structures with only one bond that differentiated them. The difference in rigidity provided different results in SAXS. Adiphenine has an aggregation number of 12, diphenhydramine has a number of 13, and pavatrine has a number of 37. In contrast to pavatrine, which did not exhibit a correlation peak, adiphenine and diphenhydramine showed correlation peaks. This indicates that none of them had an ordered phase structure but pavatrine displayed an even more disordered phase structure. Nevertheless, all three drugs were in equilibrium, and so a difference between adiphenine and pavatrine could be clearly distinguished. There were significant divergences between pavatrine and adiphenine despite not being able to determine binding isotherms for all three drugs. Based on this, they should be less stable than diphenhydramine. They have an ester linkage, while diphenhydramine doesn't. As a result, it was not possible to confirm how self-aggregation of adiphenine, pavatrine, and diphenhydramine impacts drug release. Despite this, differences in the rigidity of the structural form may lead amphiphilic drugs to exhibit different behaviour in gels. Keywords: Amphiphilic drugs, small angle x-ray scattering, macrogels, binding isotherm, CMC, self-aggregation, phase structure, micelles.