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In this work, two technologies were used to prepare long-acting implantable dosage forms in the treatment of schizophrenia. Hot-melt extrusion (HME) as well as fused deposition modelling (FDM) were used concomitantly to create personalized 3D printed implants. Different formulations were prepared using an amorphous PLA as matrix polymer and different solid-state plasticizers. Paliperidone palmitate (PP), a heat sensitive drug prescribed in the treatment of schizophrenia was chosen as model drug. After extrusion, different formulations were characterized using DSC and XRD. Then, an in vitro dissolution test was carried out to discriminate the formulation allowing a sustained drug release of PP. The formulation showing a sustained drug release of the drug was 3D printed as an implantable dosage form. By modulating the infill, the release profile was related to the proper design of tailored dosage form and not solely to the solubility of the drug. Indeed, different release profiles were achieved over 90 days using only one formulation. In addition, a stability test was performed on the 3D printed implants for 3 months. The results showed the stability of the amorphous state of PP, independently of the temperature as well as the integrity of the matrix and the drug., SCOPUS: ar.j, info:eu-repo/semantics/published

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 formulati, Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie), info:eu-repo/semantics/nonPublished

info:eu-repo/semantics/published

Despite offering robust mechanical properties, polymer networks suffer from a lack of recyclability, reshaping, and healability. Designing stiff and remendable polymer networks that can repair under mild conditions remains a challenge to extend their field of applications. Herein, we describe a simple approach to design a nonisocyanate-based polyurethane network featuring multiresponsiveness (to humidity and temperature) and outstanding healing properties, as obtained by combining iminoboronate and boroxine chemistry. In spite of the presence of abundant dynamic bonds, the network has a high stiffness (Young's modulus of 551 MPa) and tensile strength (11 MPa). C?N iminoboronate and B-O boroxine exchange reactions at high temperature enable efficient network recycling over multiple cycles without compromising its properties. Owing to these features, 3D objects could be designed and printed. The present approach provides excellent sustainable and high-performance substitution to conventional polyurethane networks requiring the use of toxic isocyanates., SCOPUS: ar.j, info:eu-repo/semantics/published