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3D printed implantable dosage form containing an amorphous form of paliperidone palmitate

par Manini, Giuseppe
Président du jury Van Antwerpen, Pierre
Promoteur Goole, Jonathan ;Raquez, Jean-Marie
Publication Non publié, 2021-12-15

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Résumé :

Personalized or individualized medicine is considered as an innovative approach to deliver the right dose to the right person at the right time. However, current technologies producing pharmaceutical products do not address the growing need for these new therapies. The aim of this work was the preparation of long-acting implantable dosage forms in which the drug release is regulated by the polymer matrix and the design of the implant. Paliperidone palmitate (PP), was selected as model drug. Indeed, PP is sensitive to thermal degradation above its melting temperature and its amorphous state remains difficult to obtain and stabilize. The first part of this study focused on obtaining and stabilizing the amorphous form of PP. A ternary mixture based on two polymers was therefore selected to be printed as dosage forms. Following an in vitro dissolution test, different release profiles were obtained depending on the selected printing parameters. Then, the stability of the amorphous state of PP was assessed at two different temperatures. During this test, implants were placed at 4°C and 25°C ± 40% residual humidity for 3 months. In the 2nd part, a 3D printing technology reducing the number of steps required to produce a suitable formulation was studied. This technology was based on a pressure extrusion-based printing process. Polycaprolactone was chosen as biocompatible and bioresorbable polymer matrix. Two different designs have been studied, namely a ring and a disk. The goal was to compare the effect of the design on the release of PP. An in vitro dissolution test was performed over a period of 3 to 6 months. In the last part, the development of a proof of concept of a predictive model taking into account the design of the printed form was studied. The impact of different printing parameters on the drug release were studied through a Design of Experiments (DoE). Finally, a second DoE was used to predict the release of PP from complex dosage forms combining two formulations.