3D Printing Technology as a Promising Tool to Design Nanomedicine-Based Solid Dosage Forms: Contemporary Research and Future Scope

The solid dosage form is the most commonly prescribed and preferred method of drug administration, representing a significant portion of all prescriptions. This is because of high patient compliance, stability, ease of administration, handling, and transportation, high productivity, and low cost [1,2]. It is commonly administered through the oral route, which is the most preferred route of drug administration due to the possibility of self-administration, non-invasiveness, and better drug absorption to achieve local and systemic effects. A few of the solid dosage forms containing different pharmaceuticals are also administered through the rectal and vaginal routes. It avoids first-pass metabolism and gastrointestinal-related side effects to achieve local and systemic delivery of pharmaceutical products [3]. Commonly used solid dosage forms such as tablets, despite high productivity and convenient manufacturing coupled with technological advancement, are still based on conventional automated tablet presses, which rely on the same principle of tablet production with designs using dies and punches that have remained unchanged for decades [4]. Conventional tablet machines are still associated with limitations in producing flexible designs and tablet sizes to fulfill the current demand for personalized drug delivery approaches to produce customized doses with modulated drug release characteristics according to individual patients’ needs, which is the scope for future medicine in the near future [5,6,7]. The introduction of 3D (three-dimensional) printing technology has revolutionized the conventional drug manufacturing technique with its high flexibility in design according to size and on-demand production of tailored doses for customized drug delivery [8,9]. The discovery of a 3D printed product, Spritam (levetiracetam), in zip-dose technology by Aprecia Pharmaceuticals, approved by the US-FDA (United States Food and Drug Administration) in 2015, brought the focus of many researchers toward the use of 3D printing techniques as a novel and promising tool for the development of pharmaceutical products [10]. The 3D printing technique, also known as additive manufacturing, is a method of manufacturing a 3D object layer by layer using CAD (computer-aided design) [11,12]. The 3D printing technique results in the development of drug products with varied geometries and modified drug release characteristics, focusing on customized delivery of drug products [13,14]. The various types of 3D printing techniques that have been extensively used in the pharmaceutical field include deposition-based inkjet printing [15,16], powder bed deposition [17,18], extrusion-based fused deposition modeling (FDM) [19,20], pressure-assisted microsyringe (PAM) technique [21,22], laser-based selective laser sintering (SLS) [23], and stereolithography (SLA) techniques [24]. The application of nanotechnology in drug delivery has the potential to improve the biopharmaceutical attributes (improving the solubility and permeability) of drugs, enhance therapeutic efficacy, and reduce the side effects of APIs (active pharmaceutical ingredients). The 3D printing technique has been employed in the development of solid dosage forms, which exploit nanotechnology to fabricate nanomedicine-based solid dosage forms. The nanomedicine formulated through nanotechnology is further transformed into a solid dosage form by exploiting 3D printing technology as a nanomedicine-based solid dosage form. Extrusion-based 3D printing methods such as FDM and PAM are the most commonly employed techniques for the development of nanomedicine-based 3D-printed solid dosage forms. FDM is a fused deposition modeling method where the printing of thermoplastic material (in the form of filament) is carried out through an extruder nozzle of a 3D printer at an elevated temperature, which prints 3D objects/pharmaceutical products by holt-melt extrusion (HME) [25]. Whereas PAM is a pressure-assisted microsyringe technique where the printing material of semisolid consistency (such as pastes, gels, and wax) is filled in a syringe extruder to print a 3D object under pressure [26]. It is also known as the semi-solid extrusion (SSE) technique. SSE is basically a material extrusion 3D printing technology that can shape/print semi-solid materials into 3D objects/pharmaceutical products (such as tablets, suppositories, etc.) by extruding them through a heated orifice. Various nanocarrier systems, such as polymeric particles/nanoparticles [27], liposomes [28], lipid-based nanoemulsions [29], nanosuspensions [30], and SNEDDS [31,32], have been fabricated as 3D-printed pharmaceutical/biomedical products. The nanocarrier-based formulations were conventionally transferred as liquid injectables, filled-in oral capsules, or transdermal delivery systems such as nanogels, patches, etc. intended for patient administration. The emergence of 3D printing technology has provided a vital tool to develop these nanocarrier-based systems into solid dosage forms, especially in the form of oral 3D printed tablets [31,32] and also as suppositories [33] for local and systemic delivery of poorly soluble drugs. The 3D printing technology has successfully designed these nanocarrier-mediated drug delivery systems into a robust solid dosage form without hampering the nanonization characteristics of the loaded pharmaceuticals or therapeutics. The present manuscript is intended to provide a detailed discussion of the recent research developments that involved the formulation design of nanomedicine-based solid dosage forms utilizing 3D printing technology.