Poor solubility of active pharmaceutical ingredients is one of the key challenges in modern pharmaceutics, as it limits their bioavailability and therapeutic efficacy. These issues are particularly pronounced in ophthalmic formulations, where the anatomical and physiological characteristics of the eye greatly restrict drug delivery to the site of action. One of the effective approaches to overcoming these limitations is the use of cyclodextrins, which, due to their specific structure, enable the formation of inclusion complexes.
In this master’s thesis, we investigated the dynamics of dissolution and complexation processes of a selected active pharmaceutical ingredient with γ-cyclodextrin. The experimental work was carried out at Lek d. d., where various dispersion samples were prepared using OptiMax™ 1001 equipment. The system enabled precise control of process parameters and real-time monitoring of turbidity during the process. To optimize the process, we employed the Design of Experiments (DoE) method, which allowed for systematic investigation of the effects of individual parameters (temperature and complexation time, as
well as temperature and cooling method) on the efficiency of complexation with a relatively small number of experiments.
The results showed that temperature plays a crucial role in the success of the complexation process. Higher temperatures accelerated dissolution and enabled more complete complexation compared to lower ones, which was reflected in the clarification of the solutions. We also found that the cooling method significantly affects the stability of dispersions. Microscopic observation of the samples revealed that slow cooling leads to the formation of larger and heterogeneously distributed particles in the micron size range. The particle morphology was therefore directly dependent on the process parameters, particularly the cooling rate. Due to slow cooling, particle size analysis using dynamic light scattering
(Zetasizer Nano) was unsuccessful, as the particles were too large. Viscosity measurements confirmed that the rheological properties were not influenced by the time and temperature of complexation, but rather by the cooling conditions. Cooling the dispersion to a higher final temperature resulted in increased viscosity, whereas faster cooling caused a decrease in viscosity.
These findings confirm the importance of monitoring the dynamics of dissolution
(complexation) processes of active pharmaceutical ingredients with γ-cyclodextrin for achieving targeted particle size and desired viscosity of the final dispersions.
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