Semi-solid Extrusion Research Articles

3D Printing of Thermo-Sensitive Drugs.

Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations.

Semi-solid extrusion 3D printing of starch-based soft dosage forms for the treatment of paediatric latent tuberculosis infection.

The development of age-appropriate dosage forms is essential for effective pharmacotherapy, especially when long-term drug treatment is required, as in the case of latent tuberculosis infection treatment with up to 9 months of daily isoniazid (ISO). Herein, we describe the fabrication of starch-based soft dosage forms of ISO using semi-solid extrusion (SSE) 3D printing. Corn starch was used for ink preparation using ISO as model drug. The inks were characterized physicochemically and their viscoelastic properties were assessed with rheological analysis. The morphology of the printed dosage forms was visualized with scanning electron microscopy and their textural properties were evaluated using texture analysis. Dose accuracy was verified before in-vitro swelling and dissolution studies in simulated gastric fluid (SGF). Starch inks were printed with good resolution and high drug dose accuracy. The printed dosage forms had a soft texture to ease administration in paediatric patients and a highly porous microstructure facilitating water penetration and ISO diffusion in SGF, resulting in almost total drug release within 45 min. The ease of preparation and fabrication combined with the cost-effectiveness of the starting materials constitutes SSE 3D printing of starch-based soft dosage forms a viable approach for paediatric-friendly formulations in low-resource settings.

High strength and high ductility nano-Ni-Al2O3/A356 composites fabricated with nickel-plating and equal channel angle semi-solid extrusion (ECASE)

Abstract The nano-Ni-Al2O3/A356 nanocomposites prepared with nickel-plating, stir casting, and equal channel angle semi-solid extrusion (ECASE). The microstructure, tensile property, and fracture morphology of the fabricated nanocomposites have been investigated. The microstructure observation showed the nickel-plating could stimulate nucleation and break nanoparticle aggregation, resulting the matrix grains in a smaller size (63 μm) and the nanoparticles more uniform located on the grain boundary. The ECASE could further refine the grains size (23 μm) and improve the nanoparticle dispersion. Although 5 passes refine the grains to 16 μm, it would cause the particles to re-agglomerate, due to the nanoparticles exist in the semi-solid liquid phase for a long time. The fabricated nanocomposites exhibited an enhancement in both strength and ductility, about 1.2–2.5 times higher than those of the corresponding aluminum matrix composites. Due to the Orowan strengthening and fine grain strengthening, i.e., increased the number of grain boundaries and improved the resistance of particles to cooperative grain deformation. Meanwhile, the ECASE eliminated the intergranular defects and improved the grain boundary bonding. The enhanced mechanical properties of the nanocomposites were attributed to the grain boundary control increased by the nickel-plating and ECASE. The grain boundary control, such as increasing the grain boundary number, improving the particle-matrix adhesion and particle dispersion, can be applied to the development of high mechanical properties aluminum matrix composites.

Preparation of clarithromycin floating core-shell systems (CSS) using multi-nozzle semi-solid extrusion-based 3D printing

Matrix erosion is unavoidable during the release of poorly soluble drugs from gastric floating delivery system (GFDDS), which shortens the floating time and diminishes drug release. We fabricated a core-shell system (CSS) consisting of a low-density drug-loaded shell and a floating core using multi-nozzle semi-solid extrusion (SSE) 3D printing technology. The clarithromycin (CAM) loading capacity of the shell was 81.7%. The floating core paste provided structural support during printing and formed a hollow structure in CAM CSS, which increased the buoyancy in the early stage of drug release. In addition, the floating core had numerous micro-airbags that swelled when the solution penetrated the core, and generated CO2. The micro-airbag structure and CO2 generation further increased the buoyancy of CSS. The CAM CSS achieved 74.5% (w/w) drug loading, 8 h sustained release, and immediate and prolonged floating (>10 h). This structure of CSS and floating core provide a novel perspective for constructing a stable gastric floating drug delivery system.

3D Printing of Drug Nanocrystals for Film Formulations.

The aim of the study was to prepare indomethacin nanocrystal-loaded, 3D-printed, fast-dissolving oral polymeric film formulations. Nanocrystals were produced by the wet pearl milling technique, and 3D printing was performed by the semi-solid extrusion method. Hydroxypropyl methyl cellulose (HPMC) was the film-forming polymer, and glycerol the plasticizer. In-depth physicochemical characterization was made, including solid-state determination, particle size and size deviation analysis, film appearance evaluation, determination of weight variation, thickness, folding endurance, drug content uniformity, and disintegration time, and drug release testing. In drug nanocrystal studies, three different stabilizers were tested. Poloxamer F68 produced the smallest and most homogeneous particles, with particle size values of 230 nm and PI values below 0.20, and was selected as a stabilizer for the drug-loaded film studies. In printing studies, the polymer concentration was first optimized with drug-free formulations. The best mechanical film properties were achieved for the films with HPMC concentrations of 2.85% (w/w) and 3.5% (w/w), and these two HPMC levels were selected for further drug-loaded film studies. Besides, in the drug-loaded film printing studies, three different drug levels were tested. With the optimum concentration, films were flexible and homogeneous, disintegrated in 1 to 2.5 min, and released the drug in 2–3 min. Drug nanocrystals remained in the nano size range in the polymer films, particle sizes being in all film formulations from 300 to 500 nm. When the 3D-printed polymer films were compared to traditional film-casted polymer films, the physicochemical behavior and pharmaceutical performance of the films were very similar. As a conclusion, 3D printing of drug nanocrystals in oral polymeric film formulations is a very promising option for the production of immediate-release improved- solubility formulations.

3D printed furosemide and sildenafil tablets: Innovative production and quality control

Three-dimensional (3D) printing of pharmaceuticals has the potential to revolutionise personalised medicine but is as yet largely unexplored. A proof-of-concept study of a novel heated, piston-driven semi-solid extrusion 3D printer was performed by producing furosemide and sildenafil tablets for paediatric patients. The average weight of the tablets was 141.1 mg (RSD 1.26%). The acceptance values of the content uniformity were 4.2–10.6 (concentration RSD 0.41–0.63%), 4.8–8.9 (concentration RSD 0.76–0.97%) and 6.6–9.2 (concentration RSD 0.94–1.44%) for furosemide 2 mg, 10 mg and sildenafil 4 mg, respectively. The dissolution rate limiting step was the dissolving and eroding of the tablet matrix and showed an immediate release. The tablets complied to the requirements of the European Pharmacopoeia (EP) for uniformity of mass (EP 2.9.5), content uniformity (EP 2.9.40) and conventional release (EP 2.9.3). While they complied, not all of these quality tests for tablets might be suitable for 3D printed tablets due to the layering of the tablets and the small batch production. To assess adequate layer adhesion adjusted friability (EP 2.9.7) and resistance to crushing (EP 2.9.8) tests are proposed.

An overview on 3D Printed Medicine

Three-dimensional printing (3DP) is a digitally-controlled additive manufacturing technique used for fast prototyping. This paper reviews various 3D printing techniques like Selective Laser Sintering (SLS), Fused Deposition Modeling, (FDM), Semi-solid extrusion (SSE), Stereolithography (SLA), Thermal Inkjet (TIJ) Printing, and Binder jetting 3D Printing along with their application in the field of medicine. Normal medicines are based on the principle of “one-size-fits-all”. This is not true always, it is possible medicine used for curing one patient is giving some side effects to another. To overcome this drawback “3D Printed medicines” are developed. In this paper, 3D printed medicines forming different Active Pharmaceutical Ingredients (API) are reviewed. Printed medicines are capable of only curing the diseases, not for the diagnosis. Nanomedicines have “theranostic” ability which combines therapeutic and diagnostic. Nanoparticles are used as the drug delivery system (DDS) to damaged cells’ specific locations. By the use of nanomedicine, the fast recovery of the disease is possible. The plant-based nanoparticles are used with herbal medicines which give low-cost and less toxic medication called nanobiomedicine. 4D and 5D printing technology for the medical field are also enlightened in this paper.

Preparation of High-Drug-Loaded Clarithromycin Gastric-Floating Sustained-Release Tablets Using 3D Printing.

The high-drug-loaded sustained-release gastric-floating clarithromycin (CAM) tablets were proposed and manufactured via semisolid extrusion (SSE)-based 3D printing. The physical and mechanical properties, such as dimensions, weight variation, friability, and hardness, were accessed according to the quality standards of Chinese Pharmacopoeia (Ch.P). The interactions among the drug-excipients were evaluated via differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) techniques. Next, the rheological properties of the paste and the effect of the excipients and solvents were evaluated. Finally, a very high drug-loading of up to 81.7% (w/w) with the sustain release time of 8 h (125 mg) and 12 h (250 mg) was achieved. The results revealed the potential of SSE for achieving a high drug loading and identified the suitable properties of the paste for SSE-based 3D printing.

Printing Methods in the Production of Orodispersible Films.

Orodispersible film (ODF) formulations are promising and progressive drug delivery systems that are widely accepted by subjects across all the age groups. They are traditionally fabricated using the most popular yet conventional method called solvent casting method. The most modern and evolving method is based on printing technologies and such printed products are generally termed as printed orodispersible films (POFs). This modern technology is well suited to fabricate ODFs across different settings (laboratory or industrial) in general and in a pharmacy setting in particular. The present review provides an overview of various printing methods employed in fabricating POFs. Particularly, it provides insight about preparing POFs using inkjet, flexographic, and three-dimensional printing (3DP) or additive manufacturing techniques like filament deposition modeling, hot-melt ram extrusion 3DP, and semisolid extrusion 3DP methods. Additionally, the review is focused on patenting trends in POFs using ESPACENET, a European Patent Office search database. Finally, the review captures future market potential of 3DP in general and ODFs market potential in particular.

Optimization of semisolid extrusion (pressure-assisted microsyringe)-based 3D printing process for advanced drug delivery application

3D printing of pharmaceutical formulations requires juggling between the material properties and the printing process to achieve the geometry of the 3D printed products with the desired dose and release. The purpose of the current investigation is to identify the material suitability for semisolid extrusion-based 3D printing of advanced drug delivery system. In this study, the semisolid extrusion-based 3D printing technique was optimized to print a controlled release shell as a vehicle/carrier for oral drug delivery system. The consistency of the printable paste was optimized by screening different solvents for the polymer of interest (cellulose acetate as optimum) to achieve the desired continuous and uniform extrudability behavior. The polarity of the solvent played important role in the selection of the suitable solvent for the optimization process. The nozzle shape (tapered tip as optimum) and the nozzle diameter (630 µm as optimum) were found to be also significantly influenced by extrusion behavior. The printing pressure (60 psi) and speed (4 mm/s) were optimized to reach the required rate of extrusion during the 3D printing process. The thickness and the width of the printed layers have contributed to the creation of the standard triangle language (STL) G-code for the printing of the 3D drug delivery system. It was found that the first printed layer deposited on a particular type of substrate plays a significant role to influence the spreadable behavior of extruded materials. Finally, the present study design proposes a rational guideline for the semisolid extrusion-based 3D printing of pharmaceutical products of specific interest for personalized medicine.

Coaxial semi-solid extrusion and ionotropic alginate gelation: A successful duo for personalized floating formulations via 3D printing

With the aim to fulfill the patient-centered approach of precision medicine, in this research, innovative floating drug delivery systems have been developed through the use of alginate matrix and fully characterized. Particularly, to exploit the ionotropic gelation of alginate, a customized coaxial extruder for Semi-solid Extrusion 3D printing, has been used for the simultaneous dispensing of ink gel (sodium alginate 6% w/v) and crosslinking gel (hydroxyethyl cellulose 3 %w/v, calcium chloride 0.1M and Tween 85 0.1% v/v). The latter also loaded with Propranolol Hydrochloride 12.5%w/v. A novel single-step process gelation for the extemporaneous gelation of loaded oral systems has been therefore developed.These technologically advanced formulations showed high printing reproducibility in manufacturing different models (mass of a single layer 535.41 ± 40.00 mg with an average drug loading efficiency of 85% w/w) and similar release behavior, paving the way for their customization in terms of drug dosages via this pioneering process.

3D Printing and Nanotechnology: A Multiscale Alliance in Personalized Medicine

Abstract3D printing and nanotechnology have been two important tools in the development of therapeutic approaches for personalized medicine. More recently, their alliance has been improved in an effort to build innovative, versatile, multifunctional, and/or smart medical and pharmaceutical products. Therefore, an extensive review about scientific studies that ally 3D printing and nanomaterials in the development of new approaches for pharmaceutical and medical applications for the treatment and prevention of diseases is presented here. The articles are classified into five categories according to their main application: Cell growth and tissue engineering, antimicrobial, drug delivery, stimulus‐response, and theranostics. Semisolid extrusion, inorganic nanoparticles, and cell growth and tissue engineering are the most reported 3D printing technique, type of nanomaterial, and application, respectively. The increase in papers dedicated to these areas is also notable, especially in the 2019 and 2020, when semisolid extrusion became the most used technique, overcoming fused deposition modelling. In fact, this review highlights that the possibility of an alliance between 3D printing and nanotechnology for the production of multiscale materials is undoubtedly a great opportunity for knowledge and innovation in the pharmaceutical and medical area.

3D-printing of solid lipid tablets from emulsion gels

Interest in 3D-printing technologies for pharmaceutical manufacturing of oral dosage forms is driven by the need for personalized medicines. Most research to date has focused on printing of polymeric-based drug delivery systems at high temperatures. Furthermore, oral formulation development is continuously challenged by the large number of poorly water-soluble drugs, which require more advanced enabling formulations to improve oral bioavailability. In this work, we used semi-solid extrusion (SSE) printing of emulsion gels with three types of emulsified lipid-based formulations (LBFs) to produce solid lipid tablets incorporating the poorly water-soluble drug, fenofibrate. Tablets were successfully 3D-printed from emulsion gels using SSE at room temperature, making the methodology particularly useful for thermolabile compounds. The tablets were well-defined in mass and disintegrated rapidly (<15 min). Importantly, the oil droplet size reconstituted after dispersion of the tablets and subsequent lipid digestion was similar to traditional liquid LBFs. This work demonstrates the successful use of SSE for fabricating solid lipid tablets based on emulsion gels. The method is further promising for on demand production of personalized dosage forms, necessary for flexible dosage adjustment in e.g., pediatric patients, when poorly water-soluble compounds constitute the core of the therapy.

Three-Dimensional (3D)-Printed Zero-Order Released Platform: a Novel Method of Personalized Dosage Form Design and Manufacturing.

In 2017, there are 451 million people with diabetes worldwide. These figures were expected to increase to 693 million by 2045. The research and development of hypoglycemic drugs has become a top priority. Among them, sulfonylurea hypoglycemic drugs such as glipizide are commonly used in non-insulin-dependent type II diabetes. In order to adapt to the wide range of hypoglycemic drugs and the different individual needs of patients, this topic used glipizide as a model drug, and prepared glipizide preparations with 3D printing technology. The purpose of this study was to investigate the prescription applicability and control-release behavior of structure and explore the application prospects of 3D printing personalized drug delivery formulations. This article aims to establish a production process for personalized preparations based on 3D printing technology. The process is easy to obtain excipients, universal prescriptions, flexible dosages, exclusive customization, and integrated automation. In this paper, the UV method was used to determine the in vitro release and content analysis method of glipizide; the physical and chemical properties of the glipizide were investigated. The established analysis method was inspected and evaluated, and the experimental results met the methodological requirements. Glipizide controlled-release tablets were prepared by the semisolid extrusion (SSE) method using traditional pharmaceutical excipients combined with 3D printing technology. The formulation composition, in vitro release, and printing process parameters of the preparation were investigated, and the final prescription and process parameters (traveling speed 6.0-7.7mm/s and extruding speed 0.0060-0.0077mm/s) were selected through comprehensive analysis. The routine analysis results of the preparation showed that the performance of the preparation meets the requirements. In order for 3D printing technology to play a better role in community medicine and telemedicine, this article further explored the universality of the above prescription and determined the scope of application of prescription drugs and dosages. Glipizide, gliclazide, lornoxicam, puerarin, and theophylline were used as model drugs, and the range of drug loading percentage was investigated. The results showed when the solubility of the drug is 9.45 -8.34mg/mL, and the drug loading is 3-43%; the release behavior is similar.

3D-Printed Veterinary Dosage Forms-A Comparative Study of Three Semi-Solid Extrusion 3D Printers.

Currently, the number of approved veterinary medicines are limited, and human medications are used off-label. These approved human medications are of too high potencies for a cat or a small dog breed. Therefore, there is a dire demand for smaller doses of veterinary medicines. This study aims to investigate the use of three semi-solid extrusion 3D printers in a pharmacy or animal clinic setting for the extemporaneous manufacturing of prednisolone containing orodispersible films for veterinary use. Orodispersible films with adequate content uniformity and acceptance values as defined by the European Pharmacopoeia were produced with one of the studied printers, namely the Allevi 2 bioprinter. Smooth and flexible films with high mechanical strength, neutral pH, and low moisture content were produced with a high correlation between the prepared design and the obtained drug amount, indicating that the Allevi 2 printer could successfully be used to extemporaneously manufacture personalized doses for animals at the point-of-care.

3D PRINTING OF PHARMACEUTICALS – LEADING TREND IN PHARMACEUTICAL INDUSTRY AND FUTURE PERSPECTIVES

3D printing technology is a rapid prototyping process based on computer-aided design software that is proficient to construct solid objects with various geometrics by depositing numerous layers in a sequence. The major advantages of three-dimensional printing (3DP) technology over the traditional manufacturing of pharmaceuticals include the customization of medications with individually adjusted doses, on-demand tailored manufacturing, unprecedented flexibility in the design, manufacturing of complex and sophisticated solid dosage forms, and economic benefits. Recently, many researchers have been invested their efforts in applying 3DP technology to the pharmaceutical development of drug products and different drug delivery systems. Selective laser sintering, fused deposition modeling, semi-solid extrusion, stereolithography, etc., are the multiple 3DP technologies that can be established in several customized and programmable medicines. Sublingual, orodispersible, and fast-dissolving drug delivery formulations by 3DP technology have been already manufactured. Controlled-release formulations with different characteristics, doughnut-shaped multi-layered tablets with linear release kinetics, and drug-loaded tablets with modified-release characteristics are recently fabricated using 3DP. However, few 3DP methods produce uneven shapes of dosage forms and comparatively porous structures. Cost of transition, adaptation to the existing facility, achieving regulatory approval, etc., are the present challenges that can restrict the extensive application of 3DP technology to pharmaceutical products. Intense research work for modifying the 3DP methods is simultaneously sustained for by-passing the flaws and current limitations of this technology. 3DP technology can act as a convenient and potential tool for the pharmaceutical industry which will set a revolutionary manufacturing style in the near future to facilitate patient-centered health care.

3D Printed Tacrolimus Rectal Formulations Ameliorate Colitis in an Experimental Animal Model of Inflammatory Bowel Disease.

The aim of this study was to fabricate novel self-supporting tacrolimus suppositories using semisolid extrusion 3-dimensional printing (3DP) and to investigate their efficacy in an experimental model of inflammatory bowel disease. Blends of Gelucire 44/14 and coconut oil were employed as lipid excipients to obtain suppository formulations with self-emulsifying properties, which were then tested in a TNBS (2,4,6-trinitrobenzenesulfonic acid) induced rat colitis model. Disease activity was monitored using PET/CT medical imaging; maximum standardized uptake values (SUVmax), a measure of tissue radiotracer accumulation rate, together with body weight changes and histological assessments, were used as inflammatory indices to monitor treatment efficacy. Following tacrolimus treatment, a significant reduction in SUVmax was observed on days 7 and 10 in the rat colon sections compared to non-treated animals. Histological analysis using Nancy index confirmed disease remission. Moreover, statistical analysis showed a positive correlation (R2 = 71.48%) between SUVmax values and weight changes over time. Overall, this study demonstrates the effectiveness of 3D printed tacrolimus suppositories to ameliorate colitis and highlights the utility of non-invasive PET/CT imaging to evaluate new therapies in the preclinical area.

I Spy with My Little Eye: A Paediatric Visual Preferences Survey of 3D Printed Tablets.

3D printing (3DP) in the pharmaceutical field is a disruptive technology that allows the preparation of personalised medicines at the point of dispensing. The paediatric population presents a variety of pharmaceutical formulation challenges such as dose flexibility, patient compliance, taste masking and the fear or difficulty to swallow tablets, all factors that could be overcome using the adaptable nature of 3DP. User acceptability studies of 3D printed formulations have been previously carried out in adults; however, feedback from children themselves is essential in establishing the quality target product profile towards the development of age-appropriate medicines. The aim of this study was to investigate the preference of children for different 3D printed tablets (Printlets™) as an important precursor to patient acceptability studies. Four different 3DP technologies; digital light processing (DLP), selective laser sintering (SLS), semi-solid extrusion (SSE) and fused deposition modeling (FDM) were used to prepare placebo printlets with similar physical attributes including size and shape. A single-site, two-part survey was completed with participants aged 4–11 years to determine their preference and opinions based on visual inspection of the printlets. A total of 368 participants completed an individual open questionnaire to visually select the best and worst printlet, and 310 participants completed further non-compulsory open questions to elaborate on their choices. Overall, the DLP printlets were the most visually appealing to the children (61.7%) followed by the SLS printlets (21.2%), and with both the FDM (5.4%) and SSE (11.7%) printlets receiving the lowest scores. However, after being informed that the SSE printlets were chewable, the majority of participants changed their selection and favoured this printlet, despite their original choice, in line with children’s preference towards chewable dosage forms. Participant age and sex displayed no significant differences in printlet selection. Printlet descriptions were grouped into four distinct categories; appearance, perceived taste, texture and familiarity, and were found to be equally important when creating a quality target product profile for paediatric 3D printed formulations. This study is the first to investigate children’s perceptions of printlets, and the findings aim to provide guidance for further development of paediatric-appropriate medicines using different 3DP technologies.

Improved microstructures of AZ31 magnesium alloy by semi-solid extrusion

The microstructure evolution and mechanical properties of AZ31 magnesium alloy during semi-solid extrusion (SSE) has been studied and compared with traditional extrusion (TE). The results show that non-equilibrium crystallization and plastic deformation occur simultaneously in the semi-solid extrusion process. Throughout the SSE process, the nucleation rate of new fine grains is significantly higher than that of the TE, which is the result of combined nucleation of crystallization and dynamic recrystallization. Twinning can be hardly activated during the SSE process, because the restraint between deformed grains is largely reduced due to the good fluidity of the semi-solid Mg alloy. The Mg alloys extruded by the SSE is characterized for homogeneous microstructure with fine grain size, weakened texture and improved mechanical properties.

Development of methylcellulose-based sustained-release dosage by semisolid extrusion additive manufacturing in drug delivery system.

The objective of this study is to fabricate customized dosage forms using extrusion-based 3D printing for the sustained delivery of theophylline. The therapeutic paste was prepared by combining various doses of theophylline (0, 75, 100, and 125 mg) with different concentrations of methylcellulose (MC) A4M (8, 10, and 12%). The paste was then 3D printed into semisolid tablets under optimized printing conditions. The rheological properties of printing pastes were related to the 3D printability. Our results indicated that to be 3D printed using the current platform, the storage modulus (G') of the printing paste should be higher than the loss modulus (G″) during the frequency sweep (0.1-600 rad/s), and the tan δ should fall in the range of 0.25-0.27 at 0.63 rad/s. The printed tablets formulated with 10% MC showed the highest overall quality, considering the aspects of resolution, texture, and shape retention regardless of the dosage. The scanning electron microscopy images indicated that the cross-linked structure of MC A4M formed the microscale porous microstructure, which has the potential to embed the theophylline, thus delayed the release through the barrier effect. The in vitro dissolution test revealed that the 3D printed tablets exhibited a sustained release during the first 12 hr. The findings in this study will support the development of customized, personalized medicine with improved efficacy.