Expanding the Manufacturing Approaches for Gastroretentive Drug Delivery Systems with 3D Printing Technology.

Gastroretentive drug delivery systems (GRDDSs) have gained substantial attention in the last 20 years due to their ability to retain the drug in the stomach for an extended time, thus promoting an extended release and high bioavailability for a broad range of active pharmaceutical ingredients (APIs) that are pH-sensitive and/or have a narrow absorption window. The currently existing GRDDSs include floating, expanding, mucoadhesive, magnetic, raft-forming, ion-exchanging, and high-density systems. Although there are seven types of systems, the main focus is on floating, expanding, and mucoadhesive systems produced by various techniques, 3D printing being one of the most revolutionary and currently studied ones. This review assesses the newest production technologies and briefly describes the in vitro and in vivo evaluation methods, with the aim of providing a better overall understanding of GRDDSs as a novel emerging strategy for targeted drug delivery.

Polyvinyl Alcohol, a Versatile Excipient for Pharmaceutical 3D Printing.

Three-dimensional (3D) printing in the pharmaceutical field allows rapid manufacturing of a diverse range of pharmaceutical dosage forms, including personalized items. The application of this technology in dosage form manufacturing requires the judicious selection of excipients because the selected materials must be appropriate to the working principle of each technique. Most techniques rely on the use of polymers as the main material. Among the pharmaceutically approved polymers, polyvinyl alcohol (PVA) is one of the most used, especially for fused deposition modeling (FDM) technology. This review summarizes the physical and chemical properties of pharmaceutical-grade PVA and its applications in the manufacturing of dosage forms, with a particular focus on those fabricated through FDM. The work provides evidence on the diversity of dosage forms created using this polymer, highlighting how formulation and processing difficulties may be overcome to get the dosage forms with a suitable design and release profile.

Development of a Bilayer Tablet by Fused Deposition Modeling as a Sustained-Release Drug Delivery System.

Three-dimensional printing by fused deposition modeling (FDM) coupled with hot-melt extrusion (HME) is a point of convergence of research efforts directed toward the development of personalized dosage forms. In addition to the customization in terms of shapes, sizes, or delivered drug doses, the modulation of drug release profiles is crucial to ensure the superior efficacy and safety of modern 3D-printed medications compared to those of conventional ones. Our work aims to solidify the groundwork for the preparation of 3D-printed tablets that ensure the sustained release of diclofenac sodium. Specifically, we achieved the fast release of a diclofenac sodium dose to allow for the prompt onset of its pharmacological effect, further sustaining by the slow release of another dose to maintain the effect over a prolonged timeframe. In this regard, proper formulation and design strategies (a honeycomb structure for the immediate-release layer and a completely filled structure for the sustained-release layer) were applied. Secondarily, the potential of polyvinyl alcohol to function as a multifaceted polymeric matrix for both the immediate and slow-release layers was explored, with the objective of promoting the real-life applicability of the technique by downsizing the number of materials required to obtain versatile pharmaceutical products. The present study is a step forward in the translation of HME-FDM-3DP into a pharmaceutical manufacturing methodology.

Development of Diclofenac Sodium 3D Printed Cylindrical and Tubular-Shaped Tablets through Hot Melt Extrusion and Fused Deposition Modelling Techniques.

The present study aimed to develop 3D printed dosage forms, using custom-made filaments loaded with diclofenac sodium (DS). The printed tablets were developed by implementing a quality by design (QbD) approach. Filaments with adequate FDM 3D printing characteristics were produced via hot melt extrusion (HME). Their formulation included DS as active substance, polyvinyl alcohol (PVA) as a polymer, different types of plasticisers (mannitol, erythritol, isomalt, maltodextrin and PEG) and superdisintegrants (crospovidone and croscarmellose sodium). The physicochemical and mechanical properties of the extruded filaments were investigated through differential scanning calorimetry (DSC), X-ray diffraction (XRD) and tensile measurements. In addition, cylindrical-shaped and tubular-shaped 3D dosage forms were printed, and their dissolution behaviour was assessed via various drug release kinetic models. DSC and XRD results demonstrated the amorphous dispersion of DS into the polymeric filaments. Moreover, the 3D printed tablets, regardless of their composition, exhibited a DS release of nearly 90% after 45 min at pH 6.8, while their release behaviour was effectively described by the Korsmeyer-Peppas model. Notably, the novel tube design, which was anticipated to increase the drug release rate, proved the opposite based on the in vitro dissolution study results. Additionally, the use of crospovidone increased DS release rate, whereas croscarmellose sodium decreased it.

QbD guided development of immediate release FDM-3D printed tablets with customizable API doses.

The objective of this work was to develop a fused deposition modeling (FDM) 3D printed immediate release (IR) tablet with flexibility in adjusting the dose of the active pharmaceutical ingredient (API) by scaling the size of the dosage form and appropriate drug release profile steadiness to the variation of dimensions or thickness of the deposited layers throughout the printing process. Polyvinyl alcohol-based filaments with elevated API content (50% w/w) were prepared by hot melt extrusion (HME), through systematic screening of polymeric formulations with different drug loadings, and their printability was evaluated by means of mechanical characterization. For the tablet fabrication step by 3D printing (3DP), the Quality by Design (QbD) approach was implemented by employing risk management strategies and Design of Experiments (DoE). The effects of the tablet design, tablet size and the layer height settings on the drug release and the API content were investigated. Between the two proposed original tablet architectures, the honeycomb configuration was found to be a suitable candidate for the preparation of IR dosage forms with readily customizable API doses. Also, a predictive model was obtained, which assists the optimization of variables involved in the printing phase and thereby facilitates the tailoring process.

Polyvinyl Alcohol-Based 3D Printed Tablets: Novel Insight into the Influence of Polymer Particle Size on Filament Preparation and Drug Release Performance.

Three-dimensional printing (3DP) by fused deposition modeling (FDM) has gained momentum as a promising pharmaceutical manufacturing method due to encouraging forward-looking perspectives in personalized medicine preparation. The current challenges the technology has for applicability in the fabrication of solid dosage forms include the limited range of suitable pharmaceutical grade thermoplastic materials. Hence, it is important to investigate the implications of variable properties of the polymeric carrier on the preparation steps and the final output, as versatile products could be obtained by using the same material. In this study, we highlighted the influence of polyvinyl alcohol (PVA) particle size on the residence time of the mixtures in the extruder during the drug-loaded filament preparation step and the consequent impact on drug release from the 3D printed dosage form. We enhanced filament printability by exploiting the plasticizing potential of the active pharmaceutical ingredient (API) and we explored a channeled tablet model as a design strategy for dissolution facilitating purposes. Our findings disclosed a new perspective regarding material considerations for the preparation of PVA-based solid dosage forms by coupling hot melt extrusion (HME) and FDM-3DP.