Novel Gastroretentive Floating Pulsatile Drug Delivery System Produced via Hot-Melt Extrusion and Fused Deposition Modeling 3D Printing

Abstract

This study was performed to develop novel core-shell gastroretentive floating pulsatile drug delivery systems using a hot-melt extrusion-paired fused deposition modeling (FDM) 3D printing and direct compression method. Hydroxypropyl cellulose (HPC) and ethyl cellulose (EC)-based filaments were fabricated using hot-melt extrusion technology and were utilized as feedstock material for printing shells in FDM 3D printing. The directly compressed theophylline tablet was used as the core. The tablet shell to form pulsatile floating dosage forms with different geometries (shell thickness: 0.8, 1.2, 1.6, and 2.0 mm; wall thickness: 0, 0.8, and 1.6 mm; and % infill density: 50, 75, and 100) were designed, printed, and evaluated. All core-shell tablets floated without any lag time and exhibited good floating behavior throughout the dissolution study. The lag time for the pulsatile release of the drug was 30 min to 6 h. The proportion of ethyl cellulose in the filament composition had a significant (p < 0.05) effect on the lag time. The formulation (2 mm shell thickness, 1.6 mm wall thickness, 100% infill density, 0.5% EC) with the desired lag time of 6 h was selected as an optimized formulation. Thus, FDM 3D printing is a potential technique for the development of complex customized drug delivery systems for personalized pharmacotherapy.

3D Printed Tablets (Printlets) with Braille and Moon Patterns for Visually Impaired Patients

“…At present, 3D printing is often used to produce engineering prototypes due to its fast production speed and cost-effectiveness [20][21][22][23]. In the field of drug delivery, diverse constructs were already prepared using 3D printing ranging from drug-eluting implants [24][25][26][27] to medical devices [28][29][30], and personalised solid oral dosage forms [31][32][33][34][35][36][37][38][39]. In particular, 3D printing was shown to offer novel solutions to problems faced by specific patient groups [40][41][42][43][44].…”

3D Printing of Pharmaceuticals and Drug Delivery Devices

“…This method of drug delivery minimises adverse effects and can increase patient compliance. This method of printing also allows the use of thermolabile drugs to be delivered through this system, as the inner core is not directly exposed to the high temperatures of FDM printing [4].…”

In-Depth Study into Polymeric Materials in Low-Density Gastroretentive Formulations

“…Some specific components of the formulations, such as stearic acid [60,148] and stearyl alcohol [149] are necessary as a processing aid for HME. In addition, low Tg polymers such as HPC [60][61][62]150], Gelucire ® [119] and poly(vinylpyrrolidone-random-vinyl acetate) (PVP/VA) [150] are commonly used.…”

“…The extrudates obtained by HME can also be used for 3D printing for the preparation of multilayered dosage forms with special designs or applicability [147,151]. For example, the preparation of HPC-based tablets combining HME and 3D printing techniques have been reported for the controlled release of domperidone [62] and theophylline [60], showing buoyancy over 10 h. Dumpa et al have fabricated, by means of HME/3D printing technologies, filaments of HPC/EC, which were used for the manufacture of core-shell gastroretentive floating tablets with pulsatile delivery of theophylline (the lag time for the pulsatile release of the drug was from 30 min to 6 h) [61]. The same group has recently reported the preparation of floating tablets for the administration of cinnarizine using HPC and Kollidon ® PVP/VA64 (random copolymer of vinylpyrrolidone and vinyl acetate, ratio 60:40) as matrix forming polymers [150].…”

“…Owing to its low Tg, HPC has been used as the main matrix-forming polymer in formulations prepared by hot-melt extrusion and 3D printing technologies, implying that the formulations could be processed at a relatively low temperature [60][61][62]. HPC has demonstrated its capacity to yield bioadhesive films [63].…”