Investigating the Use of Magnetic Nanoparticles As Alternative Sintering Agents in Selective Laser Sintering (SLS) 3D Printing of Oral Tablets.

Selective laser sintering (SLS) is a single-step, three-dimensional printing (3DP) process that is gaining momentum in the manufacturing of pharmaceutical dosage forms. It also offers opportunities for manufacturing various pharmaceutical dosage forms with a wide array of drug delivery systems. This research aimed to introduce carbonyl iron as a multifunctional magnetic and heat conductive ingredient for the fabrication of oral tablets containing isoniazid, a model antitubercular drug, via SLS 3DP process. Furthermore, the effects of magnetic iron particles on the drug release from the SLS printed tablets under a specially designed magnetic field was studied. Optimization of tablet quality was performed by adjusting SLS printing parameters. The independent factors studied were laser scanning speed, hatching space, and surface/chamber temperature. The responses measured were printed tablets' weight, hardness, disintegration time, and dissolution performance. It has been observed that, for the drug formulation with carbonyl iron, due to its inherent thermal conductivity, sintering tablets required relatively lower laser energy input to form the tablets of the same quality attributes as the other batches that contained no magnetic particles. Also, printed tablets with carbonyl iron released 25% more drugs under a magnetic field than those without it. It can be claimed that magnetic nanoparticles appear as an alternative conductive material to facilitate the sintering process during SLS 3DP of dosage forms.

Novel 3D Printed Modular Tablets Containing Multiple Anti-Viral Drugs: a Case of High Precision Drop-on-Demand Drug Deposition.

3D printed drug delivery systems have gained tremendous attention in pharmaceutical research due to their inherent benefits over conventional systems, such as provisions for customized design and personalized dosing. The present study demonstrates a novel approach of drop-on-demand (DoD) droplet deposition to dispense drug solutions precisely on binder jetting-based 3D printed multi-compartment tablets containing 3 model anti-viral drugs (hydroxychloroquine sulfate - HCS, ritonavir and favipiravir). The printing pressure affected the printing quality whereas the printing speed and infill density significantly impacted the volume dispersed on the tablets. Additionally, the DoD parameters such as nozzle valve open time and cycle time affected both dispersing volume and the uniformity of the tablets. The solid-state characterization, including DSC, XRD, and PLM, revealed that all drugs remained in their crystalline forms. Advanced surface analysis conducted by microCT imaging as well as Artificial Intelligence (AI)/Deep Learning (DL) model validation showed a homogenous drug distribution in the printed tablets even at ultra-low doses. For a four-hour in vitro drug release study, the drug loaded in the outer layer was released over 90%, and the drug incorporated in the middle layer was released over 70%. In contrast, drug encapsulated in the core was only released about 40%, indicating that outer and middle layers were suitable for immediate release while the core could be applied for delayed release. Overall, this study demonstrates a great potential for tailoring drug release rates from a customized modular dosage form and developing personalized drug delivery systems coupling different 3D printing techniques.

Emerging 3D printing technologies for drug delivery devices: Current status and future perspective.

The 'one-size-fits-all' approach followed by conventional drug delivery platforms often restricts its application in pharmaceutical industry, due to the incapability of adapting to individual pharmacokinetic traits. Driven by the development of additive manufacturing (AM) technology, three-dimensional (3D) printed drug delivery medical devices have gained increasing popularity, which offers key advantages over traditional drug delivery systems. The major benefits include the ability to fabricate 3D structures with customizable design and intricate architecture, and most importantly, ease of personalized medication. Furthermore, the emergence of multi-material printing and four-dimensional (4D) printing integrates the benefits of multiple functional materials, and thus provide widespread opportunities for the advancement of personalized drug delivery devices. Despite the remarkable progress made by AM techniques, concerns related to regulatory issues, scalability and cost-effectiveness remain major hurdles. Herein, we provide an overview on the latest accomplishments in 3D printed drug delivery devices as well as major challenges and future perspectives for AM enabled dosage forms and drug delivery systems.

Ligand-modified Biopolymeric Nanoparticles as Efficient Tools for Targeted Cancer Therapy.

Non-specific distribution of chemotherapeutic agents in the body where they affect both cancer as well as normal cells resulting in serious side effects is the major reason for the high mortality rate of cancer. Thus, there is a need for developing targeted delivery strategies specially employing nanoplatform-based cancer therapies that provide specific targeting to tumor cells. In this regard, biopolymeric nanoplatforms such as liposomes, protein- and polysaccharide- based nanoparticles have gained more attention due to their biocompatibility, biodegradability and less toxicity. In terms of targeting, monoclonal antibodies (mAbs), folic acid (FA) and transferrin (Tf) can be considered as the moieties to be attached to the nanoplatforms to deliver their payload to its site of action. This review article focuses on the recent progress in the field of targeted drug and gene delivery systems with emphasizes on liposomes, protein (specially human and bovine serum albumin)-based nanoparticles and polysaccharide (specially chitosan and dextran)-based nanoparticles as the biopolymeric nanoplatforms, which are decorated with mAbs, FA and Tf as the targeting ligands.