The aim of this thesis is to develop an integrated experimental/computational approach for the design of a gastroretentive drug delivery system, produced by FDM 3D printing technology. The approach was tested on three commercial thermoplastic polyurethane elastomers (TPU-E) characterized by different degrees of Shore Hardness. Initially, a comprehensive experimental investigation was conducted in order to fully characterize the thermo-mechanical response of TPU. In particular, uniaxial tensile tests at different test conditions, in terms of strain rate and environment were performed on TPU filaments. Then, 3D-printed dumbbells were also tested to verify thermo-mechanical response compared to the non-extruded filament. The data obtained were used to define the most suitable constitutive model to describe the hyper-elastic behavior of the material. The main results, obtained from the previous tests, can be summarized as follows: i) the material exhibits non-linear behavior, with very limited time dependence; ii) through cyclic tests, a significant residual deformation was observed at unloading in the first cycle; iii) neither the printing process nor the conditioning treatment in an acidic environment, which imitates the stomach, significantly alters the material's response. Subsequently, a characterization of the performance of the 3D printed device was conducted. The system consists of a rigid part and a flexible part. The study focused on defining the mechanical response of the flexible part. The tests conducted on the prototype were 'funnel test' and the capsule opening test. In the first test, the prototype was pushed through a funnel in order to simulate the forced passage through the pylorus and assess the maximum value of force, in the second test the prototype was folded in a gelatin capsule and the opening process in contact with water was observed. The results obtained in the experimental tests were compared with those obtained in the simulations. The proposed approach provided useful results and recommendations for the design of gastroretentive DDS.
L'obiettivo di questa tesi è sviluppare un approccio integrato sperimentale/computazionale per la progettazione di un sistema di rilascio gastro-retentivo, prodotto con la tecnologia di stampa 3D FDM. L'approccio è stato testato su tre elastomeri poliuretanici termoplastici commerciali (TPU-E) caratterizzati da diversi gradi di durezza. Inizialmente, è stata condotta un'indagine sperimentale completa per caratterizzare la risposta termomeccanica del TPU. In particolare, sono state eseguite prove di trazione mono-assiale in diverse condizioni di prova, in termini di velocità di deformazione e ambiente, su filamenti di TPU. Successivamente, ossi di cane stampati in 3D sono stati testati per verificare la risposta termomeccanica rispetto al filamento non estruso. I dati ricavati sono stati impiegati per definire il modello costitutivo più adatto a descrivere il comportamento iper-elastico del materiale. I risultati principali possono essere riassunti come segue: i) il materiale presenta un comportamento non lineare, con una dipendenza temporale molto limitata; ii) attraverso test ciclici, è stata osservata una significativa deformazione residua allo scarico nel primo ciclo; iii) né il processo di stampa né il trattamento di condizionamento in un ambiente acido, che imita lo stomaco, alterano significativamente la risposta del materiale. Successivamente, è stata condotta una caratterizzazione delle prestazioni del dispositivo stampato in 3D. Il sistema è composto da una parte rigida e da una parte flessibile. Lo studio si è concentrato sulla definizione della risposta meccanica della parte flessibile eseguendo due test principali per valutare la performance. Nel “funnel test”, il prototipo è spinto attraverso un imbuto per simulare il passaggio forzato attraverso il piloro e valutare il valore massimo della forza, nel secondo test il prototipo è ripiegato in una capsula di gelatina e si osserva il processo di apertura a contatto con l'acqua. I risultati ottenuti nelle prove sperimentali sono stati confrontati con i valori numerici ottenuti da un'analisi agli elementi finiti. L'approccio proposto ha fornito risultati utili per la progettazione di DDS gastroretentivi.
Design of a gastroretentive drug delivery system
Rossi, Margherita
2021/2022
Abstract
The aim of this thesis is to develop an integrated experimental/computational approach for the design of a gastroretentive drug delivery system, produced by FDM 3D printing technology. The approach was tested on three commercial thermoplastic polyurethane elastomers (TPU-E) characterized by different degrees of Shore Hardness. Initially, a comprehensive experimental investigation was conducted in order to fully characterize the thermo-mechanical response of TPU. In particular, uniaxial tensile tests at different test conditions, in terms of strain rate and environment were performed on TPU filaments. Then, 3D-printed dumbbells were also tested to verify thermo-mechanical response compared to the non-extruded filament. The data obtained were used to define the most suitable constitutive model to describe the hyper-elastic behavior of the material. The main results, obtained from the previous tests, can be summarized as follows: i) the material exhibits non-linear behavior, with very limited time dependence; ii) through cyclic tests, a significant residual deformation was observed at unloading in the first cycle; iii) neither the printing process nor the conditioning treatment in an acidic environment, which imitates the stomach, significantly alters the material's response. Subsequently, a characterization of the performance of the 3D printed device was conducted. The system consists of a rigid part and a flexible part. The study focused on defining the mechanical response of the flexible part. The tests conducted on the prototype were 'funnel test' and the capsule opening test. In the first test, the prototype was pushed through a funnel in order to simulate the forced passage through the pylorus and assess the maximum value of force, in the second test the prototype was folded in a gelatin capsule and the opening process in contact with water was observed. The results obtained in the experimental tests were compared with those obtained in the simulations. The proposed approach provided useful results and recommendations for the design of gastroretentive DDS.| File | Dimensione | Formato | |
|---|---|---|---|
|
2023_maggio_Rossi_Tesi.pdf
non accessibile
Dimensione
1.88 MB
Formato
Adobe PDF
|
1.88 MB | Adobe PDF | Visualizza/Apri |
|
2023_maggio_Rossi_Executive_summary.pdf
non accessibile
Dimensione
829.78 kB
Formato
Adobe PDF
|
829.78 kB | Adobe PDF | Visualizza/Apri |
I documenti in POLITesi sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/10589/208257