Effect of Cooling and Heating Rates on Polymorphic Transformations and Gelation of Tripalmitin Solid Lipid Nanoparticle (SLN) Suspensions

Solid lipid nanoparticle (SLN) suspensions undergo a phase transition from the α- to β-polymorphic forms, which is accompanied by particle aggregation and gel formation. These processes are both time and temperature dependent, and so it is important to study the impact of cooling rates (CRs) and heating rates (HRs) on polymorphic transformations, particle aggregation, and gelation. Rheology measurements indicated that the temperature where gelation was first observed during cooling (T _gel) decreased with increasing CRs, with SLN suspensions remaining fluid at HR ≥ 5 °C/min. On the other hand, the temperature where gelation was first observed during heating of stable SLN suspensions increased with increasing HRs: 18, 24, 31, and 45 °C at 2, 5, 10, and 20 °C/min, respectively. When the melted SLN suspensions were cooled again, two exothermic peaks were observed in the differential scanning calorimetry scans at 39 (which was attributed to coalesced oil) and 19 °C (which was attributed to stable SLN). With increasing CR, the enthalpy of the coalescence peak (ΔH _CO) decreased, while that of the supercooled SLN (ΔH _SLN) increased. With increasing HR, ΔH _CO decreased and ΔH _SLN increased, with no coalescence being observed at HR ≥ 10 °C/min. These results show that increasing the CRs or HRs retard the α→β polymorphic transformation, which increased the stability of SLN against aggregation and retarded gelation. In addition, this study shows that the careful selection of HRs and CRs is required to examine polymorphic transformations and the stability of SLN suspensions.