Oral lyophilisates are solid pharmaceutical formulations which are characterized by disintegration and release of the active ingredient within a few seconds after application to the oral cavity. The active ingredient can be partially absorbed in the oral cavity, avoiding the »first-pass« effect and improving its bioavailability. Patient compliance is also increased due to rapid disintegration and ease of ingestion, which is especially important in psychiatric, pediatric, and geriatric patients.The main purpose of the master's thesis was to develop the formulation of oral lyophilisates, i.e. the selection of suitable excipients and their concentrations in the solutions that were lyophilized. Given that lyophilization is an energy-intensive and financially demanding process, especially the rate of primary drying. We optimized the latter phase by implementing aggressive drying conditions.Mannitol was used as the filler of the lyophilisates, and as the binder, we got to choose from gelatin, PVP K25, and a mixture of both. The active ingredient olanzapine was added to the most promising formulations. After each lyophilization cycle, the lyophilization process was evaluated using process graphs. We evaluated the appearance, measured the thickness, mass, strength, and disintegration time of the final products. Residual water content was determined by thermogravimetric analysis (TGA), and phase changes of liquid samples before lyophilization as well as solid products were determined by differential dynamic calorimetry (DSC).We found that the most suitable appearance of the lyophilisate was shown by the formulation with 6 % (w/w) of excipients and mass ratio of gelatin:PVP:mannitol = 1:2:5. PVP provided optimal water solubility, while the addition of gelatin strengthened the lyophilisate matrix thus preventing crumbling and cracking.The disintegration time of such oral lyophilisates was 5 seconds and the residual water content was less than 4 % (w/w). Thermal analysis of liquid samples by DSC was used to determine the glass transition temperature of the critically concentrated solution (Tg '), which is an important parameter for planning the conditions of the lyophilization cycle. By analyzing solid samples with DSC, we determined the glass transition temperature of the lyophilisate (Tg), which is related to the physical stability of the product. The aforementioned parameter showed that the optimal formulation was stable at room temperature. By using aggressive conditions, we shortened the primary drying phase by 50 %. This significantly increased the cost and time efficiency of the lyophilization process, without affecting the quality of the final product.
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