Oral lyophilisates are solid dosage forms known for their rapid disintegration and dispersion once in contact with water. After their administration, a rapid release of active substance takes place in the oral cavity what enables its earlier absorbtion via the buccal and oesophageal mucosa consequently avoiding the first-pass metabolism. In addition, the rapid disintegration of oral lyophilisates results in much easier swallowing what improves compliance among geriatric, pediatric, and psychiatric patients especially. In the master thesis, we have done an optimization of formulations for oral lyophilisates. The active substance of olanzapine was incorporated into the formulations that exhibited adequate physical and thermal properties. The liquid formulations contained 6 % (w/w) of excipients with a ratio of mannitol: PVP = 5:2. Firstly, we have examined how the addition of gelatine to the formulation impacts the appearance and disintegration time of the lyophilisates. Secondly, we have replaced the short-chain PVP K25 with the long-chain PVP K90. In the third step, we have developed the formulations containing glycine or cross-linked sodium carmellose in addition to the before-mentioned composition of PVP, mannitol, and gelatine. We have also done the replacement of the plain gelatin with the enzyme-treated gelatin. Finally, we have incorporated the active substance of olanzapine of 5 mg and 10 mg into the formulations that have shown the best properties. The appearance, weight, and disintegration time of the resulting products were evaluated. We have found out that the replacement of the PVP K25 with the PVP K90 contributes to the improved disintegration time in the formulations with higher proportions of gelatine. The addition of glycine has proved to be very useful as it halved the disintegration time of the lyophilizates compared to the standard formulation. The physical properties of the lyophilisates were not significantly affected when the cross-linked sodium carmellose was introduced to the formulation. The replacement of the plain gelatine with the enzyme-treated gelatine has provided lyophilizates with the shortest disintegration time (1 second) however they were less suitable for handling due to their brittleness. The incorporation of the active substance has not impacted the formulation significantly. The glass transition temperature of the critically concentrated frozen solution (Tg`) was determined for the liquid formulations by differential dynamic calorimetry. Based on the comparison of the measured Tg` and the product temperature we have concluded the drying process was held under aggressive conditions. The glass transition temperature (Tg) of final lyophilisates was determined and the formulations were shown to be well stable at room temperature.
|
