Expandable drug delivery system for gastric retention based on shape memory polymers: Development via 4D printing and extrusion

Abstract

Several diseases would benefit from prolonged drug release provided by systems retained in the stomach for extended time periods. Expandable gastroretentive devices are administered in a collapsed configuration enabling swallowing and regain in situ their native shape having larger spatial encumbrance, thus hindering voidance through the wide open pylorus. An expandable system for gastric retention was here proposed relying on the shape memory behavior of pharmaceutical-grade poly(vinyl alcohol). Different original configurations to be recovered upon exposure to aqueous fluids at 37 °C, potentially enabling gastric retention, were conceived. Prototypes containing allopurinol were directly manufactured by fused deposition modeling or shaped by purposely-designed templates from hot melt extruded rods immediately after production. Various temporary shapes, in principle suitable for administration, were programmed by manual deformation of samples by means of specific templates, under defined temperature conditions. In 0.1N hydrochloric solution at 37 °C, the prototypes recovered their original shape, reaching the desired spatial encumbrance within few minutes. Release from the samples, although of relatively short duration, was independent of the original shape and processing undergone, and was noticeably slowed down by application of Eudragit RS/RL-based coatings.

Steering the Clinical Translation of Delivery Systems for Drugs and Health Products

“…Furthermore, these flexible modified dosage forms could comply with prescribed dosing regimens due to differences in age and weight of child. The water-induced shape-memory response of pharmaceutical-grade poly(vinyl alcohol) (PVA) of different molecular weight was recently demonstrated [76,77]. Based on the ability of PVA-based items fabricated by fused deposition modeling (FDM) to take on a temporary shape and recover the original one upon contact with aqueous fluids at body temperature, 4D printing (i.e., 3D printing of objects that undergo changes in configuration upon exposure to an external non-mechanical stimulus) was proposed for the development of retentive systems intended for intragastric and intravesical drug delivery.…”

Retentive drug delivery systems based on shape memory materials

“…Finally, PVA of pharmaceutical grade has been proposed for HME and FDM 3D printing of prototype devices having, on the one hand, a temporary configuration fitting into 00el size hard‐gelatin capsules and, on the other, a possibly retentive original shape to be recovered in the gastric fluid following water‐induced activation of the polymer shape memory response . Permanent shapes incorporating wide void volumes, such as S‐ or atom‐like ones and cylindrical or conical coils, have been conceived and explored.…”

“…(a) Virtual models of templates and (b) photographs of corresponding PVA‐based gastroretentive device prototypes obtained from extruded rods of 1 mm in diameter. Reproduced from Reference . [Color figure can be viewed at wileyonlinelibrary.com]…”

“…Photographs of PVA‐based gastroretentive device prototypes obtained by (top string) HME and (bottom string) FDM, having original helix shapes, programmed to take on a temporary supercoiled configuration, inserted into hard‐gelatin capsules, and immersed in HCl 0.1 N at 37 ± 0.5 °C. Reproduced from Reference . [Color figure can be viewed at wileyonlinelibrary.com]…”

Injection Molded Capsules for Colon Delivery Combining Time-Controlled and Enzyme-Triggered Approaches

“…In the field of oral modified-release, great efforts have been made since the 1990s to develop drug delivery systems (DDSs) able to release the conveyed drug to specific regions of the gastrointestinal tract [1][2][3][4][5][6][7]. In particular, the colon drew considerable attention as a target site for the treatment of local disorders, such as inflammatory bowel diseases (e.g., ulcerative colitis and Crohn's disease) and irritable bowel syndrome, as well as for the prevention of colorectal adenocarcinoma [8][9][10].…”