Currently, fused deposition modeling (FDM) is a 3D printing technology that has been most widely used to develop innovative drug delivery approaches for overcoming the limitations of oral drug administration. Propranolol has a short plasma half-life and is well soluble in acidic environments. Thus, this study aimed to develop a gastro-floating 3D printed device (GFD) to sustain the release of propranolol in the stomach as a gastro-retentive drug delivery system. The polylactic acid (PLA) was selected to fabricate the GFD. An air chamber was included in the interior construction of the GFD design for buoyancy. The number of open channels on the side wall of GFD was modified to regulate release. The propranolol gel formulation was composed of a mixture of propranolol and polyvinylpyrrolidone (PVP) at the weight ratio of 6:5 and was then loaded into GFDs using a syringe. GFD exhibited a floating ability of more than 24 h with low standard deviation (SD) values of weight variation and shape dimension. The propranolol release from GFD shows sustained release properties in the simulated gastric environment without lag time. The 4 and 5 channels of GFD exhibited sustained drug release for 6 h. In addition, the duration of sustained release for 8 h was achieved from the GFD with 2 and 3 channels. The kinetic release of propranolol from GFDs was the best fit with zero-order. Thus, the GFDs could be designed to control the drug release according to each patient, which has the potential for applying personalized gastro-retentive drug delivery in various medications. Graphical abstract

Background: Isosorbide dinitrate (ISDN) and hydralazine hydrochloride (HDZ) are dual cardiovascular drugs used to treat heart failure. However, the drugs have limitations such as short plasma half-life, low bioavailability, and potential for tolerance of the nitrate component. To address the need for prolonged drug release, a floating dual-compartment drug delivery system was developed to provide controlled drug release under simulated gastric dissolution conditions. Objectives: This study aimed to develop floating dual-compartment devices (FDCDs) to contain ISDN and HDZ gel and modify drug release under simulated gastric conditions. Methods: The FDCD was designed in a cylindrical shape consisting of an air chamber on the upper part for floating ability, and two compartments for loaded drug gel and controlling the drug release rate. Fused deposition modeling (FDM) was selected to fabricate FDCDs using polylactic acid (PLA) filament. The ISDN formulation varied the ratio of polyvinylpyrrolidone (PVP) to achieve drug release for 12 h. The HDZ formulation was optimized by varying the ratio of PVP and hydroxypropyl methylcellulose (HPMC) to extend drug release at 24 h. Results: The shape dimension and weight variation in the FDCDs showed low standard deviation (SD). FDCDs exhibited immediate floating, resisted overturning, and demonstrated in vitro floating ability for more than 24 h. The formulation ISDN3 at a PVP: drug: water ratio of 5:2:3 exhibited complete release at 12 h, while the formulation of HDZ1 at an HPMC: PVP: drug: water ratio of 0.3:2.5:2:5.2 showed complete release within 24 h. The ISDN3- and HDZ1-loaded FDCDs demonstrated prolonged release behavior, with ISDN and HDZ release profiles showing the best fit to the zero-order and Higuchi models, respectively, based primarily on the coefficient of determination (R²), while root mean square error (RMSE) was used as a complementary measure of fitting error. Conclusions: These findings suggest that the developed dual-drug-loaded FDCD has potential as a dual-drug oral delivery platform for simultaneous delivery of ISDN and HDZ with prolonged drug release characteristics and further development of oral combination drug delivery systems.

The oral administration of 5-fluorouracil (5-FU) is limited by low bioavailability, poor membrane permeability, and non-specificity to the target site. The objective of this study was to develop 5-FU-loaded mucoadhesive nanoparticles (NPs) to enhance mucoadhesion in the colon and to achieve colon-targeted drug delivery by fabricating a dual pulsed-release 3D-printed device (DPRD) as a colon-targeted drug delivery system (CTDDS). The chitosan-grafted maleimide (CS-M6A) was used to prepare 5-FU-loaded CS-M6A NPs for mucoadhesive properties. The characterizations of 5-FU-loaded CS-M6A NPs were conducted, including mucoadhesive properties, permeability, and cytotoxicity against colorectal cancer cells. The DPRD was designed to consist of an outer chamber and an inner chamber with varying wall thicknesses (1, 2, and 3 mm) to control the lag time of drug release. The release of the drug from the DPRD with enteric coating was evaluated using in vitro dissolution. The results showed the successful development of 5-FU-loaded Cs-M6A NPs with an approximate size of 315 nm (PDI = 0.14), enhanced mucoadhesive properties, and inhibition of cancer cell proliferation. Additionally, the devices exhibited biphasic drug release. The initial drug release was detected at 5 h, which corresponded with the adjustment of the medium to the colonic environment. The secondary release showed a delayed release of approximately 7-10 h, with sustained release, with more than 90% of the drug released over 16 h. Therefore, this study demonstrated a novel technique, combining drug-loaded mucoadhesive NPs with 3D-printed devices to achieve controlled and sustained CTDDS.

Background: Prednisolone conventional tablet is a drug commonly used to treat inflammatory bowel disease (IBD). However, the long-term use of high doses of prednisolone can lead to gastric irritation, risk of infection, and other systemic complications. These limitations of the drug can be overcome by using three-dimensional (3D) printing technology with pH-dependent approaches. Objectives: This study aimed to develop 3D-printed devices containing prednisolone tablets and gel with an enteric coating for colon-targeted modified release. Methods: 3D-printed drug-containing devices (CDDs) were designed and divided into two classifications, including devices for prednisolone tablets (PTDs) and devices for prednisolone gel (PGDs). CDDs were fabricated using fused deposition modeling (FDM). The morphology of the CDDs was assessed using a microscope. The tablets and gel of prednisolone were loaded into CDDs depending on the type of device, and the CDDs were coated by Eudragit^® S100. In vitro drug release studies were investigated using dissolution apparatus II in simulated gastric medium (pH 1.2) for 2 h, simulated intestinal medium (pH 6.8) for 2 h, and simulated colonic medium (pH 7.4) for 20 h. Results: The prednisolone-loaded CDDs with enteric coating were protected from drug release before reaching the colon. The dissolution profile of prednisolone from CDDs showed no drug release in the simulated gastric and simulated intestinal medium, with drug release initiated under simulated colonic medium and sustained release maintained for up to 24 h. Conclusions: These findings showed that CDDs have potential for delivering prednisolone to the colon with controlled drug release under simulated in vitro gastrointestinal conditions. Furthermore, these CDDs could be adapted for other drugs.