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This review provides a comprehensive overview of additive manufacturing (AM) or 3D-printing (3DP) applications in the pharmaceutical industry, with a particular focus on the critical role of polymer selection. By providing insights into how material properties influence the 3DP process and the quality of the final product, this review aims to contribute to a better understanding of the interplay between polymers and pharmaceutical 3DP. As 3DP technologies are increasingly integrated into pharmaceutical sciences, this review contributes insights into the nuanced process of polymer selection, serving mainly as a foundational guide for researchers and formulators new to the subject seeking to harness the full potential of pharmaceutical 3DP by understanding the physicochemical properties, roles, and functions of used polymers in 3D-printed dosage forms and medical devices. [ABSTRACT FROM AUTHOR]

The successful integration of hot-melt extrusion (HME) and fused deposition modelling (FDM) depends on a better understanding of the impact of environmental conditions on the printability of formulations, since they significantly affect the properties of the raw materials, whose control is crucial to enable three-dimensional printing (3DP). Hence, the objective of this work was to investigate the correlation between the environmental settings and the properties of paroxetine (PRX)-loaded filaments, previously produced by HME, which affect printability by FDM. The influence of different drying methods of the physical mixtures (PMs) and HME-filaments (FILs) on the quality and printability of these products was also assessed. The printability of FILs was evaluated in terms of the water content, and the mechanical and thermal properties of the products. Stability studies and physicochemical, thermal, and in vitro dissolution tests were carried out on the 3D-printed tablets. Stability studies demonstrated the high ductility of the PRX loaded FILs, especially under high humidity conditions. Under low humidity storage conditions (11% RH), the FILs became stiffer and were successfully used to feed the FDM printer. Water removal was slow when carried out passively in a controlled atmosphere (desiccator) or accelerated by using active drying methods (heat or microwave). Pre-drying of the PRX/excipients and/or PMs did not show any positive effect on the printability of the FIL. On the contrary, dry heat and, preferably, microwave mediated drying processes were shown to reduce the holding time required for successful FDM printing, enabling on-demand production at the point of care. [ABSTRACT FROM AUTHOR]

Currently, there is a shortage of pediatric medicines on the market, and 3D printing technology can more flexibly produce personalized medicines to meet individual needs. The study developed a child-friendly composite gel ink (carrageenan-gelatin), created 3D models by computer-aided design technology, then produced personalized medicines using 3D printing to improve the safety and accuracy of medication for pediatric patients. An in-depth understanding of the printability of different formulations was obtained by analyzing the rheological and textural properties of different gel inks and observing the microstructure of different gel inks, which guided the formulation optimization. Through formulation optimization, the printability and thermal stability of gel ink were improved, and F6 formulation (carrageenan: 0.65%; gelatin: 12%) was selected as the 3D printing inks. Additionally, a personalized dose linear model was established with the F6 formulation for the production of 3D printed personalized tablets. Moreover, the dissolution tests showed that the 3D printed tablets were able to dissolve more than 85% within 30 min and had similar dissolution profiles to the commercially available tablets. This study demonstrates that 3D printing is an effective manufacturing technique that allows for flexible, rapid, and automated production of personalized formulations. [ABSTRACT FROM AUTHOR]

Currently, there is a shortage of pediatric medicines on the market, and 3D printing technology can more flexibly produce personalized medicines to meet individual needs. The study developed a child-friendly composite gel ink (carrageenan-gelatin), created 3D models by computer-aided design technology, then produced personalized medicines using 3D printing to improve the safety and accuracy of medication for pediatric patients. An in-depth understanding of the printability of different formulations was obtained by analyzing the rheological and textural properties of different gel inks and observing the microstructure of different gel inks, which guided the formulation optimization. Through formulation optimization, the printability and thermal stability of gel ink were improved, and F6 formulation (carrageenan: 0.65%; gelatin: 12%) was selected as the 3D printing inks. Additionally, a personalized dose linear model was established with the F6 formulation for the production of 3D printed personalized tablets. Moreover, the dissolution tests showed that the 3D printed tablets were able to dissolve more than 85% within 30 min and had similar dissolution profiles to the commercially available tablets. This study demonstrates that 3D printing is an effective manufacturing technique that allows for flexible, rapid, and automated production of personalized formulations.

Three-dimensional (3D) printing technology enables the design of new drug delivery systems for personalised medicine. Polymers that can be molten are needed to obtain extruded filaments for Fused Deposition Modelling (FDM), one of the most frequently employed techniques for 3D printing. The aim of this work was to evaluate the extrusion process and the physical appearance of filaments made of a hydrophilic polymer and a non-molten model drug. Metformin was used as model drug and Affinisol™ 15LV as the main carrier. Drug-loaded filaments were obtained by using a single-screw extruder and, subsequently, their printability was tested. Blends containing up to a 60% and 50% drug load with 5% and 7.5% of auxiliary excipients, respectively, were successfully extruded. Between the obtained filaments, those containing up to 50% of the drug were suitable for use in FDM 3D printing. The studied parameters, including residence time, flow speed, brittleness, and fractal dimension, reflect a critical point in the extrusion process at between 30–40% drug load. This finding could be essential for understanding the behaviour of filaments containing a non-molten component. [ABSTRACT FROM AUTHOR]

The utilized 3D printhead employs an innovative hot-melt extrusion (HME) design approach being fed by drug-loaded polymer granules and making filament strands obsolete. Oscillatory rheology is a key tool for understanding the behavior of a polymer melt in extrusion processes. In this study, small amplitude shear oscillatory (SAOS) rheology was applied to investigate formulations of model antihypertensive drug Metoprolol Succinate (MSN) in two carrier polymers for pharmaceutical three-dimensional printing (3DP). For a standardized printing process, the feeding polymers viscosity results were correlated to their printability and a better understanding of the 3DP extrudability of a pharmaceutical formulation was developed. It was found that the printing temperature is of fundamental importance, although it is limited by process parameters and the decomposition of the active pharmaceutical ingredients (API). Material characterization including differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA) of the formulations were performed to evaluate component miscibility and ensure thermal durability. To assure the development of a printing process eligible for approval, all print runs were investigated for uniformity of mass and uniformity of dosage in accordance with the European Pharmacopoeia (Ph. Eur.).

Three-dimensional (3D) printing technology enables the design of new drug delivery systems for personalised medicine. Polymers that can be molten are needed to obtain extruded filaments for Fused Deposition Modelling (FDM), one of the most frequently employed techniques for 3D printing. The aim of this work was to evaluate the extrusion process and the physical appearance of filaments made of a hydrophilic polymer and a non-molten model drug. Metformin was used as model drug and Affinisol™ 15LV as the main carrier. Drug-loaded filaments were obtained by using a single-screw extruder and, subsequently, their printability was tested. Blends containing up to a 60% and 50% drug load with 5% and 7.5% of auxiliary excipients, respectively, were successfully extruded. Between the obtained filaments, those containing up to 50% of the drug were suitable for use in FDM 3D printing. The studied parameters, including residence time, flow speed, brittleness, and fractal dimension, reflect a critical point in the extrusion process at between 30–40% drug load. This finding could be essential for understanding the behaviour of filaments containing a non-molten component.

Selective laser sintering (SLS) is a rapid prototyping technique for the production of three-dimensional objects through selectively sintering powder-based layer materials. The aim of the study was to investigate the effect of energy density (ED) and formulation factors on the printability and characteristics of SLS irbesartan tablets. The correlation between formulation factors, ED, and printability was obtained using a decision tree model with an accuracy of 80%. FT-IR results revealed that there was no interaction between irbesartan and the applied excipients. DSC results indicated that irbesartan was present in an amorphous form in printed tablets. ED had a significant influence on tablets’ physical, mechanical, and morphological characteristics. Adding lactose monohydrate enabled faster drug release while reducing the possibility for printing with different laser speeds. However, formulations with crospovidone were printable with a wider range of laser speeds. The adjustment of formulation and process parameters enabled the production of SLS tablets with hydroxypropyl methylcellulose with complete release in less than 30 min. The results suggest that a decision tree could be a useful tool for predicting the printability of pharmaceutical formulations. Tailoring the characteristics of SLS irbesartan tablets by ED is possible; however, it needs to be governed by the composition of the whole formulation.

3D printing is a new emerging technology in the pharmaceutical manufacturing landscape. Its potential advantages for personalized medicine have been widely explored and commented on in the literature over recent years. More recently, the selective laser sintering (SLS) technique has been investigated for oral drug-delivery applications. Thus, this article reviews the work that has been conducted on SLS 3D printing for the preparation of solid oral forms (SOFs) from 2017 to 2020 and discusses the opportunities and challenges for this state-of-the-art technology in precision medicine. Overall, the 14 research articles reviewed report the use of SLS printers equipped with a blue diode laser (445–450 nm). The review highlights that the printability of pharmaceutical materials, although an important aspect for understanding the sintering process has only been properly explored in one article. The modulation of the porosity of printed materials appears to be the most interesting outcome of this technology for pharmaceutical applications. Generally, SLS shows great potential to improve compliance within fragile populations. The inclusion of “Quality by Design” tools in studies could facilitate the deployment of SLS in clinical practice, particularly where Good Manufacturing Practices (GMPs) for 3D-printing processes do not currently exist. Nevertheless, drug stability and powder recycling remain particularly challenging in SLS. These hurdles could be overcome by collaboration between pharmaceutical industries and compounding pharmacies.

Material suitability needs to be considered for the 3D printing of solid oral dosage forms (SODFs). This work aims to assess the suitability of a CO2 laser (λ = 10.6 μm) for selective laser sintering of SODFs containing copovidone and paracetamol. First, physicochemical characterization of powders (two grades of copovidone, two grades of paracetamol and their mixtures at various proportions) was conducted: particle size distribution, morphology, infrared absorbance, flowability, and compactness. Then, printing was launched, and printability of the powders was linked to their physicochemical characteristics. The properties of the sintered SODFs were evaluated (solid state, general aspect, porosity, hardness, drug content and release). Hence, it was found that as copovidone absorbs at the laser’s wavelength, sintering was feasible without using an absorbance enhancer. Also, flowability, which mainly depends on the particle size, represents the first control line for “sinterability” as a fair flow is at least required. Low compactness of copovidone and mixtures reduces the mechanical properties of the SODFs but also increases porosity, which can modulate drug release. Moreover, the drug did not undergo degradation and demonstrated a plasticizer effect by lowering the heating temperature. In conclusion, this work proves the applicability of CO2 laser SLS printer to produce SODFs.

Three-dimensional (3D) printing offers the greatest potential to revolutionize the future of pharmaceutical manufacturing by overcoming challenges of conventional pharmaceutical operations and focusing design and production of dosage forms on the patient’s needs. Of the many technologies available, fusion deposition modelling (FDM) is considered of the lowest cost and higher reproducibility and accessibility, offering clear advantages in drug delivery. FDM requires in-house production of filaments of drug-containing thermoplastic polymers by hot-melt extrusion (HME), and the prospect of connecting the two technologies has been under investigation. The ability to integrate HME and FDM and predict and tailor the filaments’ properties will extend the range of printable polymers/formulations. Hence, this work revises the properties of the most common pharmaceutical-grade polymers used and their effect on extrudability, printability, and printing outcome, providing suitable processing windows for different raw materials. As a result, formulation selection will be more straightforward (considering the characteristics of drug and desired dosage form or release profile) and the processes setup will be more expedite (avoiding or mitigating typical processing issues), thus guaranteeing the success of both HME and FDM. Relevant techniques used to characterize filaments and 3D-printed dosage forms as an essential component for the evaluation of the quality output are also presented.

In the last few years, the employment of 3D printing technologies in the manufacture of drug delivery systems has increased, due to the advantages that they offer for personalized medicine. Thus, the possibility of producing sophisticated and tailor-made structures loaded with drugs intended for tissue engineering and optimizing the drug dose is particularly interesting in the case of pediatric and geriatric population. Natural products provide a wide range of advantages for their application as pharmaceutical excipients, as well as in scaffolds purposed for tissue engineering prepared by 3D printing technologies. The ability of biopolymers to form hydrogels is exploited in pressure assisted microsyringe and inkjet techniques, resulting in suitable porous matrices for the printing of living cells, as well as thermolabile drugs. In this review, we analyze the 3D printing technologies employed for the preparation of drug delivery systems based on natural products. Moreover, the 3D printed drug delivery systems containing natural products are described, highlighting the advantages offered by these types of excipients.

The high printing efficiency and easy availability of desktop digital light processing (DLP) printers have made DLP 3D printing a promising technique with increasingly broad application prospects, particularly in personalized medicine. The objective of this study was to fabricate and evaluate medical samples with external and internal structures using the DLP technique. The influence of different additives and printing parameters on the printability and functionality of this technique was thoroughly evaluated. It was observed that the printability and mechanical properties of external structures were affected by the poly(ethylene glycol) diacrylate (PEGDA) concentration, plasticizers, layer height, and exposure time. The optimal printing solutions for 3D external and internal structures were 100% PEGDA and 75% PEGDA with 0.25 mg/mL tartrazine, respectively. And the optimal layer height for 3D external and internal structures were 0.02 mm and 0.05 mm, respectively. The optimal sample with external structures had an adequate drug-loading ability, acceptable sustained-release characteristics, and satisfactory biomechanical properties. In contrast, the printability of internal structures was affected by the photoabsorber, PEGDA concentration, layer height, and exposure time. The optimal samples with internal structures had good morphology, integrity and perfusion behavior. The present study showed that the DLP printing technique was capable of fabricating implants for drug delivery and physiological channels for in vivo evaluation.

The utilized 3D printhead employs an innovative hot-melt extrusion (HME) design approach being fed by drug-loaded polymer granules and making filament strands obsolete. Oscillatory rheology is a key tool for understanding the behavior of a polymer melt in extrusion processes. In this study, small amplitude shear oscillatory (SAOS) rheology was applied to investigate formulations of model antihypertensive drug Metoprolol Succinate (MSN) in two carrier polymers for pharmaceutical three-dimensional printing (3DP). For a standardized printing process, the feeding polymers viscosity results were correlated to their printability and a better understanding of the 3DP extrudability of a pharmaceutical formulation was developed. It was found that the printing temperature is of fundamental importance, although it is limited by process parameters and the decomposition of the active pharmaceutical ingredients (API). Material characterization including differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA) of the formulations were performed to evaluate component miscibility and ensure thermal durability. To assure the development of a printing process eligible for approval, all print runs were investigated for uniformity of mass and uniformity of dosage in accordance with the European Pharmacopoeia (Ph. Eur.).

The aim of this work was to investigate the effect of process parameters on the printability of a formulation containing copovidone and paracetamol, and on the properties of solid oral forms 3D-printed through selective laser sintering. Firstly, the influence of the heating temperature was evaluated individually, and it was revealed that this parameter was critical for printability, as a sufficiently high temperature (100 °C) is necessary to avoid curling. Secondly, the effects of laser power, scan speed, and layer thickness were determined using a Box–Behnken design. The measured responses, printing yield, height, weight, hardness, disintegration time, and percentage of drug release at 10 min showed the following ranges of values: 55.6–100%, 2.92–3.96 mm, 98.2–187.2 mg, 9.2–83.4 N, 9.7–997.7 s, and 25.8–99.9%, respectively. Analysis of variance (ANOVA) proved that the generated quadratic models and the effect of the three–process parameters were significant (p < 0.05). Yield improved at high laser power, low scan speed, and increased layer thickness. Height was proportional to laser power, and inversely proportional to scan speed and layer thickness. Variations in the other responses were related to the porosity of the SOFs, which were dependent on the value of energy density. Low laser power, fast scan speed, and high layer thickness values favored a lower energy density, resulting in low weight and hardness, rapid disintegration, and a high percentage of drug release at 10 min. Finally, an optimization was performed, and an additional experiment validated the model. In conclusion, by applying a Quality by Design approach, this study demonstrates that process parameters are critical for printability, but also offer a way to personalize the properties of the SOFs. [ABSTRACT FROM AUTHOR]

3D printing is a new emerging technology in the pharmaceutical manufacturing landscape. Its potential advantages for personalized medicine have been widely explored and commented on in the literature over recent years. More recently, the selective laser sintering (SLS) technique has been investigated for oral drug-delivery applications. Thus, this article reviews the work that has been conducted on SLS 3D printing for the preparation of solid oral forms (SOFs) from 2017 to 2020 and discusses the opportunities and challenges for this state-of-the-art technology in precision medicine. Overall, the 14 research articles reviewed report the use of SLS printers equipped with a blue diode laser (445–450 nm). The review highlights that the printability of pharmaceutical materials, although an important aspect for understanding the sintering process has only been properly explored in one article. The modulation of the porosity of printed materials appears to be the most interesting outcome of this technology for pharmaceutical applications. Generally, SLS shows great potential to improve compliance within fragile populations. The inclusion of "Quality by Design" tools in studies could facilitate the deployment of SLS in clinical practice, particularly where Good Manufacturing Practices (GMPs) for 3D-printing processes do not currently exist. Nevertheless, drug stability and powder recycling remain particularly challenging in SLS. These hurdles could be overcome by collaboration between pharmaceutical industries and compounding pharmacies. [ABSTRACT FROM AUTHOR]

Selective laser sintering (SLS) is a rapid prototyping technique for the production of three-dimensional objects through selectively sintering powder-based layer materials. The aim of the study was to investigate the effect of energy density (ED) and formulation factors on the printability and characteristics of SLS irbesartan tablets. The correlation between formulation factors, ED, and printability was obtained using a decision tree model with an accuracy of 80%. FT-IR results revealed that there was no interaction between irbesartan and the applied excipients. DSC results indicated that irbesartan was present in an amorphous form in printed tablets. ED had a significant influence on tablets' physical, mechanical, and morphological characteristics. Adding lactose monohydrate enabled faster drug release while reducing the possibility for printing with different laser speeds. However, formulations with crospovidone were printable with a wider range of laser speeds. The adjustment of formulation and process parameters enabled the production of SLS tablets with hydroxypropyl methylcellulose with complete release in less than 30 min. The results suggest that a decision tree could be a useful tool for predicting the printability of pharmaceutical formulations. Tailoring the characteristics of SLS irbesartan tablets by ED is possible; however, it needs to be governed by the composition of the whole formulation.

Material suitability needs to be considered for the 3D printing of solid oral dosage forms (SODFs). This work aims to assess the suitability of a CO2 laser (λ = 10.6 μm) for selective laser sintering of SODFs containing copovidone and paracetamol. First, physicochemical characterization of powders (two grades of copovidone, two grades of paracetamol and their mixtures at various proportions) was conducted: particle size distribution, morphology, infrared absorbance, flowability, and compactness. Then, printing was launched, and printability of the powders was linked to their physicochemical characteristics. The properties of the sintered SODFs were evaluated (solid state, general aspect, porosity, hardness, drug content and release). Hence, it was found that as copovidone absorbs at the laser's wavelength, sintering was feasible without using an absorbance enhancer. Also, flowability, which mainly depends on the particle size, represents the first control line for "sinterability" as a fair flow is at least required. Low compactness of copovidone and mixtures reduces the mechanical properties of the SODFs but also increases porosity, which can modulate drug release. Moreover, the drug did not undergo degradation and demonstrated a plasticizer effect by lowering the heating temperature. In conclusion, this work proves the applicability of CO2 laser SLS printer to produce SODFs. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing offers the greatest potential to revolutionize the future of pharmaceutical manufacturing by overcoming challenges of conventional pharmaceutical operations and focusing design and production of dosage forms on the patient's needs. Of the many technologies available, fusion deposition modelling (FDM) is considered of the lowest cost and higher reproducibility and accessibility, offering clear advantages in drug delivery. FDM requires in-house production of filaments of drug-containing thermoplastic polymers by hot-melt extrusion (HME), and the prospect of connecting the two technologies has been under investigation. The ability to integrate HME and FDM and predict and tailor the filaments' properties will extend the range of printable polymers/formulations. Hence, this work revises the properties of the most common pharmaceutical-grade polymers used and their effect on extrudability, printability, and printing outcome, providing suitable processing windows for different raw materials. As a result, formulation selection will be more straightforward (considering the characteristics of drug and desired dosage form or release profile) and the processes setup will be more expedite (avoiding or mitigating typical processing issues), thus guaranteeing the success of both HME and FDM. Relevant techniques used to characterize filaments and 3D-printed dosage forms as an essential component for the evaluation of the quality output are also presented. [ABSTRACT FROM AUTHOR]

In the last few years, the employment of 3D printing technologies in the manufacture of drug delivery systems has increased, due to the advantages that they offer for personalized medicine. Thus, the possibility of producing sophisticated and tailor-made structures loaded with drugs intended for tissue engineering and optimizing the drug dose is particularly interesting in the case of pediatric and geriatric population. Natural products provide a wide range of advantages for their application as pharmaceutical excipients, as well as in scaffolds purposed for tissue engineering prepared by 3D printing technologies. The ability of biopolymers to form hydrogels is exploited in pressure assisted microsyringe and inkjet techniques, resulting in suitable porous matrices for the printing of living cells, as well as thermolabile drugs. In this review, we analyze the 3D printing technologies employed for the preparation of drug delivery systems based on natural products. Moreover, the 3D printed drug delivery systems containing natural products are described, highlighting the advantages offered by these types of excipients. [ABSTRACT FROM AUTHOR]

The high printing efficiency and easy availability of desktop digital light processing (DLP) printers have made DLP 3D printing a promising technique with increasingly broad application prospects, particularly in personalized medicine. The objective of this study was to fabricate and evaluate medical samples with external and internal structures using the DLP technique. The influence of different additives and printing parameters on the printability and functionality of this technique was thoroughly evaluated. It was observed that the printability and mechanical properties of external structures were affected by the poly(ethylene glycol) diacrylate (PEGDA) concentration, plasticizers, layer height, and exposure time. The optimal printing solutions for 3D external and internal structures were 100% PEGDA and 75% PEGDA with 0.25 mg/mL tartrazine, respectively. And the optimal layer height for 3D external and internal structures were 0.02 mm and 0.05 mm, respectively. The optimal sample with external structures had an adequate drug-loading ability, acceptable sustained-release characteristics, and satisfactory biomechanical properties. In contrast, the printability of internal structures was affected by the photoabsorber, PEGDA concentration, layer height, and exposure time. The optimal samples with internal structures had good morphology, integrity and perfusion behavior. The present study showed that the DLP printing technique was capable of fabricating implants for drug delivery and physiological channels for in vivo evaluation. [ABSTRACT FROM AUTHOR]