Additive Manufacturing of SmartEx QD 100 Designed Oral Three-Dimensional Printlets Containing Isoniazid for Immediate Gastric Release by Selective Laser Sintering.

The selection of appropriate materials and compatibility of selected materials with drugs and formulations are limiting steps in three-dimensional printing technology. In this study, SmartEx QD 100 (SM QD 100) was introduced as a novel, coprocessed, unexplored excipient that can be used in SLS-mediated 3D printing. The current study aimed to evaluate the feasibility of fabricating SM QD 100 containing INH-embedded SLS-mediated immediate gastric release tablets. The prepared physical mixtures were subjected to the fabrication of 3D printlets by using SLS-mediated 3D printing. The fabricated 3D printlets were subjected to physicochemical characterization by using various analytical techniques. After oral administration of sintered 3D printlets to rabbits, samples were collected and pharmacokinetic parameters were analyzed using the developed LC-APCI-MS/MS method. The optimized batch was able to release 100% INH within 15 min, which confirmed the immediate gastric release. Similarly, sintered 3D printlets were stable under accelerated stability conditions for three months. Finally, the pharmacokinetic parameters revealed the rate and extent of absorption of INH from sintered 3D printlets. As evidenced by in vitro and in vivo analyses, SM QD 100 was able to sinter SLS-mediated INH-embedded stable immediate gastric release tablets. SM QD 100 is a novel material for SLS-mediated 3D printing in pharmaceutical applications.

Development, Pharmacokinetics and Antimalarial Evaluation of Dose Flexible 3D Printlets of Dapsone for Pediatric Patients.

The focus of current studies was to fabricate dose flexible printlets of dapsone (DDS) for pediatric patients by selective laser sintering (SLS) 3D printing method, and evaluate its physicochemical, patient in-use stability, and pharmacokinetic attributes. Eight formulations were fabricated using Kollicoat® IR, Eudragit® L-100-55 and StarCap®as excipients and evaluated for hardness, disintegration, dissolution, amorphous phase by differential scanning calorimetry and X-ray powder diffraction, in-use stability at 30 oC/75% RH for a month, and pharmacokinetic study in Sprague Dawley rats. The hardness, and disintegration of the printlets varied from 2.6±1.0 (F4) to 7.7±0.9 (F3) N and 2.0±0.4 (F2) to 7.6±0.6 (F3) sec, respectively. The drug was partially present as an amorphous form in the printlets. The drug was completely (>85%) dissolved in 20 min. No change in drug form or dissolution extent was observed after storage at in use condition. Pharmacokinetic profiles of both formulations (tablets and printlets) were almost superimposable with no statistical difference in pharmacokinetic parameters (Tmax, Cmax, and AUC0-¥)between formulations (p>0.05). Values of EC50 (half maximal effective concentration) and EC90 (maximal concentration inducing 90% maximal response) were 0.50±0.15 and 1.32±0.26 mM, 0.41±0.06 and 1.11±0.21, and 0.42±0.13 and 1.36±0.19 mM for DDS, printlet and tablet formulations, respectively, and differences were statistically insignificant (p>0.05). In conclusion, tablet and printlet formulations are expected to be clinical similar, thus clinically interchangeable.

In Vitro and In Vivo testing of 3D-Printed Amorphous Lopinavir Printlets by Selective Laser Sinitering: Improved Bioavailability of a Poorly Soluble Drug.

The aim of this paper was to investigate the effects of formulation parameters on the physicochemical and pharmacokinetic (PK) behavior of amorphous printlets of lopinavir (LPV) manufactured by selective laser sintering 3D printing method (SLS). The formulation variables investigated were disintegrants (magnesium aluminum silicate at 5-10%, microcrystalline cellulose at 10-20%) and the polymer (Kollicoat® IR at 42-57%), while keeping printing parameters constant. Differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infrared analysis confirmed the transformation of the crystalline drug into an amorphous form. A direct correlation was found between the disintegrant concentration and dissolution. The dissolved drug ranged from 71.1 ± 5.7% to 99.3 ± 2.7% within 120 min. A comparative PK study in rabbits showed significant differences in the rate and extent of absorption between printlets and compressed tablets. The values for Tmax, Cmax, and AUC were 4 times faster, and 2.5 and 1.7 times higher in the printlets compared to the compressed tablets, respectively. In conclusion, the SLS printing method can be used to create an amorphous delivery system through a single continuous process.

Comparison of misfit and roughness of CAD-CAM ZrO, selective laser sintered CoCr and preformed Ti implant abutment crowns.

BACKGROUND: Marginal misfit and surface roughness of customized implant abutments is critical for restorative success. However, little is known about the comparison of misfit and surface roughness of CAD-CAM Zirconium oxide (ZrO), selective laser melting (SLM) Cobalt Chrome (CoCr) and preformed abutments. The aim of the study is to investigate the relation of misfit and micro-roughness of selective laser melting (SLM), preformed and CAD-CAM implant abutments. METHODS: Thirty internal connection, endosseous dental implants (Ø 4.0 mm x 10 mm, Dentium) were mounted in Polymethyl methacrylate vertically. Ten preformed Titanium alloy (Ti) abutments with 1 mm soft tissue height and Ø 4.5 mm were included as controls. Ten each of Y-TZP and SLM-CoCr, abutment/crowns were fabricated using CAD-CAM milling (CAD-CAM-ZrO) and SLM techniques. Surface micro-roughness (Ra) of the fabricated implant abutment/crown was evaluated with a 3D optical non-contact microscope. All implant restorations were torqued to implants (30 Ncm) using a Tohnichi BTGE digital torque gauge and were analyzed with Bruker micro-CT (Skyscan 1173) to detect micro-gaps at pre-selected points at implant abutment interface. The Ra and misfit data were compared using ANOVA, Tukey-Kramer, Kruskal-Wallis test and Pearson correlation (p < 0.05). RESULTS: Mean Ra among SLM CoCr abutments [0.88 (0.09) µm] were lower than CAD-CAM-ZrO and higher than preformed Ti abutments. Horizontal misfit among SLM-CoCr [45.43 (9.41) µm] and preformed Ti [36.87 (13.23) µm] abutments was not statistically different (p > 0.05). Misfit was significantly higher in Y-TZP samples compared to SLM-CoCr (p = 0.031) and preformed Ti abutments (p = 0.01). Preformed Ti abutments showed significantly lower misfit compared to SLM-CoCr abutments (p = 0.01). A positive linear correlation was observed between the surface roughness (Ra) and vertical misfit (r = 0.61, p < 0.05). CONCLUSION: SLM CoCr abutments showed rough surface compared to preformed Ti abutments, while horizontal misfit was comparable among SLM-CoCr and preformed abutments. Misfit was significantly greater in Y-TZP abutments, compared to SLM and preformed abutments. SLM abutment fabrication technique needs further improvement to provide better fit and surface topography.

Influence of various fabrication techniques and porcelain firing on the accuracy of metal-ceramic crowns.

BACKGROUND: The fit of a metal-ceramic restoration is essential to its long-term durability. Regarding marginal and internal fit, there is not enough information about the technologies used in the production of metal-ceramic restorations. The aim of this in vitro study is to compare, both before and after porcelain firing, the marginal, axial, axio-occlusal, and occlusal fit of metal-ceramic restorations manufactured using casting, additive or subtractive computer-aided design, and computer-aided manufacturing techniques (CAD/CAM). METHODS: CAD/CAM were used to create 50 prepared maxillary first molar-shaped Co-Cr die models, which were randomly divided into 5 groups (n = 10). Cobalt-chrome copings were produced by casting (C), hard metal milling (HM), soft metal milling (SM), selective laser melting (SLM), and selective laser sintering (SLS) techniques. Before and after porcelain firing, discrepancies of the copings were measured using the silicone replica technique. The data obtained by measurements with a stereomicroscope at x80 magnification were analyzed statistically in the SPSS program. The ROBUST three-way analysis of variance (ANOVA) method was used to compare the discrepancy values. RESULTS: There were statistically significant differences among fabrication methods (P < .001). The HM method showed the highest discrepancy (90.1 µm), and the C (63 µm) method showed the lowest discrepancy in terms of the die model- crown fit. The C, SLS, and SM methods (63 µm; 61.6 µm; 67.7 µm) were statistically similar (P > .001). The highest discrepancy was observed on the occlusal area (87.1 µm), and the lowest discrepancy was observed on the axial area (47.7 µm) of the coping. Porcelain firing had a decrease in the discrepancy values (P = .001). CONCLUSION: All CAD/CAM techniques are appropriate for clinical use; selective laser sintering and soft milling can be the more recommended methods for the compatibility of metal-porcelain restorations, as they have lower discrepancy values than the SLM and HM methods.

Magnetic Field Boosts the Transmembrane Transport Efficiency of Magnesium Ions from PLLA Bone Scaffold.

In the system of magnesium-loaded scaffolds, the effect of magnesium ions (Mg2+ ) on the osteogenesis induction is restricted due to the low transmembrane transport efficiency of Mg2+ into the cell, which limits the application for bone defect repair. Inspired by the fact that magnetic field can regulate ion channel proteins on the cell membrane, magnetite nanoparticle is introduced into the poly (l-lactic acid) /magnesium oxide composite in this study, and a magnetic magnesium-loaded bone scaffold is prepared via selective laser sintering . Notably, the activities of the Mg2+ channel protein (MAGT1) on the membrane of bone marrow mesenchymal stem cells (rBMSCs) are enhanced via magnetic torque effect (via integrin αV ß3/actin), under the action of static magnetic field (SMF), which promoted rBMSCs to capture Mg2+ in the microenvironment and induced osteogenesis. In vitro experiments showed that the magnetic magnesium-loaded scaffold, under the action of SMF, can accelerate the inflow of Mg2+ from surrounding microenvironment, which improved cellular activities, osteogenesis-related gene expression (ALP, Runx2, OCN, and OPN), and mineralization. Besides, in vivo skull defect repair experiments showed that the scaffolds possessed good ability to promote bone differentiation and new bone regeneration.

Three-dimensional (3D) printing in dental practice: Applications, areas of interest, and level of evidence.

OBJECTIVES: The aim of this review to overview three-dimensional (3D) printing technologies available for different dental disciplines, considering the applicability of such technologies and materials development. MATERIALS AND METHODS: Source Arksey and O'Malley's five stages framework using PubMed, EMBASE, and Scopus (Elsevier) databases managed this review. Papers focusing on 3D printing in dentistry and written in English were screened. Scientific productivity by the number of publications, areas of interest, and the focus of the investigations in each dental discipline were extracted. RESULTS: Nine hundred thirty-four studies using 3D printing in dentistry were assessed. Limited clinical trials were observed, especially in Restorative, endodontics, and pediatric dentistry. Laboratory or animal studies are not reliable for clinical success, suggesting that clinical trials are a good approach to validate the new methods' outcomes and ensure that the benefits outweigh the risk. The most common application for 3D printing technologies is to facilitate conventional dental procedures. CONCLUSIONS: The constantly improving quality of 3D printing applications has contributed to increasing the popularity of these technologies in dentistry; however, long-term clinical studies are necessary to assist in defining standards and endorsing the safe application of 3D printing in dental practice. CLINICAL RELEVANCE: The recent progress in 3D materials has improved dental practice capabilities over the last decade. Understanding the current status of 3D printing in dentistry is essential to facilitate translating its applications from laboratory to the clinical setting.

Preparation and Characterization of 3D-Printed Dose-Flexible Printlets of Tenofovir Disoproxil Fumarate.

The aim of this work was to design pediatric-friendly, dose-flexible orally disintegrating drug delivery systems (printlets) of the antiviral drug tenofovir disoproxil fumarate (TDF) by selective laser sintering (SLS) for potential use in hospitals along with other antiviral drugs. In order to obtain a consistent quality of printlets with desired properties, it is important to understand certain critical quality attributes for their main and interactions effect. The printlets were optimized by Box-Behnken's design of the experiment by varying process variables while keeping the composition constant. The composition contained 16.3% TDF, 72.7% polyvinyl pyrrolidone K16-18, 8% magnesium aluminum silicate, 3% Candurin® NXT Ruby Red, and 0.3% colloidal silicon dioxide. The process variables studied were surface (X1), chamber temperatures (X2), and laser scanning speed (X3). The range of variable levels was 75-85°C for X1, 50-70°C for X2, and 200-240 mm/s for X3, respectively. The responses studied were hardness, disintegration time, dissolution, physiochemical, and pharmacokinetic characterization. X-ray powder diffraction indicated partial or complete conversion of the crystalline drug into amorphous form in the printlets. Comparative pharmacokinetics between Viread® (generic) and printlets in rats were superimposable. Pharmacokinetic parameters showed statistically insignificant differences between the two formulations in terms of Tmax, Cmax, and AUC of (p > 0.05). Printlets were bioequivalent to Viread® as per FDA bioequivalence criteria. Thus, the SLS printing method showed the fabrication of dose-flexible printlets with quality, and in vivo performance equivalent to commercial tablets.

Very-Rapidly Dissolving Printlets of Isoniazid Manufactured by SLS 3D Printing: In Vitro and In Vivo Characterization.

The focus of this research was to understand the effects of formulation and processing variables on the very-rapidly dissolving printlets of isoniazid (INH) manufactured by the selective laser sintering (SLS) three-dimensional (3D) printing method, and to characterize their physicochemical properties, stability, and pharmacokinetics. Fifteen printlet formulations were manufactured by varying the laser scanning speed (400-500 mm/s, X1), surface temperature (100-110 °C, X2), and croscarmellose sodium (CCS, %, X3), and the responses measured were weight (Y1), hardness (Y2), disintegration time (DT, Y3), and dissolution (Y4). Laser scanning was the most important processing factor affecting the responses. DT was very rapid (≥3 s), and dissolution (>99%) was completed within 3 min. The root-mean-square error in the studied responses was low and analysis of variance (ANOVA) was statistically significant (p < 0.05). X-ray micro-computed tomography (micro-CT) images showed very porous structures with 24.6-34.4% porosity. X-ray powder diffraction and differential scanning calorimetry data indicated partial conversion of the crystalline drug into an amorphous form. The printlets were stable at 40 °C/75% RH with no significant changes in assay and dissolution. Pharmacokinetic profiles of the printlets and compressed tablets were superimposable. In conclusion, the rapidly dissolving printlets of the INH were stable, and oral bioavailability was similar to that of compositionally identical compressed tablets.

Detecting Crystallinity Using Terahertz Spectroscopy in 3D Printed Amorphous Solid Dispersions.

This study demonstrates the applicability of terahertz time-domain spectroscopy (THz-TDS) in evaluating the solid-state of the drug in selective laser sintering-based 3D printed dosage forms. Selective laser sintering is a powder bed-based 3D printing platform, which has recently demonstrated applicability in manufacturing amorphous solid dispersions (ASDs) through a layer-by-layer fusion process. When formulating ASDs, it is critical to confirm the final solid state of the drug as residual crystallinity can alter the performance of the formulation. Moreover, SLS 3D printing does not involve the mixing of the components during the process, which can lead to partially amorphous systems causing reproducibility and storage stability problems along with possibilities of unwanted polymorphism. In this study, a previously investigated SLS 3D printed ASD was characterized using THz-TDS and compared with traditionally used solid-state characterization techniques, including differential scanning calorimetry (DSC) and powder X-ray diffractometry (pXRD). THz-TDS provided deeper insights into the solid state of the dosage forms and their properties. Moreover, THz-TDS was able to detect residual crystallinity in granules prepared using twin-screw granulation for the 3D printing process, which was undetectable by the DSC and XRD. THz-TDS can prove to be a useful tool in gaining deeper insights into the solid-state properties and further aid in predicting the stability of amorphous solid dispersions.

Design, Fabrication, and Testing of a Fully 3D-Printed Pressure Sensor Using a Hybrid Printing Approach.

Pressure sensing is not a new concept and can be applied by using different transduction mechanisms and manufacturing techniques, including printed electronics approaches. However, very limited efforts have been taken to realise pressure sensors fully using additive manufacturing techniques, especially for personalised guide prosthetics in biomedical applications. In this work, we present a novel, fully printed piezoresistive pressure sensor, which was realised by using Aerosol Jet® Printing (AJP) and Screen Printing. AJ®P was specifically chosen to print silver interconnects on a selective laser sintered (SLS) polyamide board as a customised substrate, while piezoresistive electrodes were manually screen-printed on the top of the interconnects as the sensing layer. The sensor was electromechanically tested, and its response was registered upon the application of given signals, in terms of sensitivity, hysteresis, reproducibility, and time drift. When applying a ramping pressure, the sensor showed two different sensitive regions: (i) a highly sensitive region in the range of 0 to 0.12 MPa with an average sensitivity of 106 Ω/MPa and a low sensitive zone within 0.12 to 1.25 MPa with an average sensitivity of 7.6 Ω/MPa with some indeterminate overlapping regions. Hysteresis was negligible and an electrical resistance deviation of about 14% was observed in time drift experiments. Such performances will satisfy the demands of our application in the biomedical field as a smart prosthetics guide.

Flat-Top Line-Shaped Beam Shaping and System Design.

In this study, the circular Gaussian spot emitted by a laser light source is shaped into a rectangular flat-top beam to improve the scanning efficiency of a selective laser sintering scanning system. A CO2 laser with a power of 200 W, wavelength of 10.6 µm, and spot diameter of 9 mm is shaped into a flat-top spot with a length and width of 0.5 × 0.1 mm, and the mapping function and flat-top Lorentzian function are calculated. We utilize ZEMAX to optimize the aspherical cylindrical lens of the shaping system and the cylindrical lens of the focusing system. We then calculate the energy uniformity of the flat-top line-shaped beam at distances from 500 to 535 mm and study the zoom displacement of the focusing lens system. The results indicated that the energy uniformity of the flat-top beam was greater than 80% at the distances considered, and the focusing system must precisely control the displacement of the cylindrical lens in the Y-direction to achieve precise zooming.

Fabrication of Sustained-Release Dosages Using Powder-Based Three-Dimensional (3D) Printing Technology.

Three-dimensional (3D)-printed tablets prepared using powder-based printing techniques like selective laser sintering (SLS) typically disintegrate/dissolve and release the drug within a few minutes because of their inherent porous nature and loose structure. The goal of this study was to demonstrate the suitability of SLS 3DP technology for fabricating sustained-release dosages utilizing Kollidon® SR (KSR), a matrix-forming excipient composed of polyvinyl acetate and polyvinylpyrrolidone (8:2). A physical mixture (PM), comprising 10:85:5 (% w/w) of acetaminophen (ACH), KSR, and Candurin®, was sintered using a benchtop SLS 3D printer equipped with a 2.3-W 455-nm blue visible laser. After optimization of the process parameters and formulation composition, robust 3D-printed tablets were obtained as per the computer-aided design (CAD) model. Advanced solid-state characterizations by powder X-ray diffraction (PXRD) and wide-angle X-ray scattering (WAXS) confirmed that ACH remained in its native crystalline state after sintering. In addition, X-ray micro-computed tomography (micro-CT) studies revealed that the tablets contain a total porosity of 57.7% with an average pore diameter of 24.8 µm. Moreover, SEM images exhibited a morphological representation of the ACH sintered tablets' exterior surface. Furthermore, the KSR matrix 3D-printed tablets showed a sustained-release profile, releasing roughly 90% of the ACH over 12 h as opposed to a burst release from the free drug and PM. Overall, our work shows for the first time that KSR can be used as a suitable polymer matrix to create sustained-release dosage forms utilizing the digitally controllable SLS 3DP technology, showcasing an alternative technique and pharmaceutical excipient.

Accuracy Evaluation of the Computer-Designed Selective Laser Sintering Surgical Guide for Flapless Immediate Loading Dental Implants Surgery in Edentulous Jaws.

This study was designed to evaluate the accuracy of a novel computer-designed and selectively laser sintered surgical guide for flapless dental implant placement in the edentulous jaw. Fifty dental implants were placed in 11 patients with at least 1 totally edentulous jaw. Initially, cone-beam computed tomography (CBCT) was performed in each patient to define the virtual position of the dental implants based on the assessment of bone availability and the proposed dental prosthesis. After virtual planning, 3D surgical guides were printed using selective laser sintering. CBCT was repeated after the surgery, and the pre- and postoperative images were overlapped in computer-assisted design software to compare the planned and actual positions of the dental implants using a 1-sample t test. The mean ± angular standard deviation between the long axes of the planned and final dental implant positions was 4.58° ± 2.85°; the linear deviation in the coronal position was 0.87 ± 0.49 mm and in the apical region of the dental implants was 1.37 ± 0.69 mm. These differences were statistically significant (P < .001). The proposed modifications reduced the deviations, resulting in an improvement in the technique. We were able to place implants and temporary prostheses using the present protocol, taking into account the differences between the planned and final positions of the dental implants.

Current development status of additive manufacturing technologies for fabricating removable partial denture frameworks: a literature review.

AIM: The aim of the present study was to review the current development status of additive manufacturing (AM) technology for fabricating frameworks for removable partial dentures (RPDs) considering fit accuracy, surface condition, and mechanical strength. METHODS: A search of the databases of MEDLINE, Cochrane Library, and Science Direct was conducted using definite keywords ("removable partial denture" or "framework" or "dental prosthesis design") and ("additive manufacturing technology" or "rapid prototyping" or "3D-printing"). RESULT: A total of 23 articles were selected according to certain inclusion criteria. The direct AM techniques were applied to manufacture metal RPD frameworks consisting of selective laser melting (SLM), selective laser sintering (SLS), and metal binder jetting (MBJ). The SLM technique showed a good surface and mechanical strength, but low accuracy. The SLS technique showed higher accuracy than indirect AM, but further studies are required. The MBJ technique showed lower accuracy and a rougher surface than the conventional method. CONCLUSION: AM techniques can produce RPD frameworks within the acceptable range for clinical practice; however, more clinical studies are needed.

Accuracy of surface adaptation of complete denture bases fabricated using milling, material jetting, selective laser sintering, digital light processing, and conventional injection molding.

AIM: Milling-based, subtractive fabrication of digital complete dentures represents the computer-engineered manufacturing method of choice. However, efficient additive manufacturing technologies might also prove beneficial for the indication. The aim of the present study was to evaluate the accuracy of surface adaptation of complete denture bases fabricated using subtractive, additive, and conventional manufacturing techniques. MATERIALS AND METHODS: A standardized edentulous maxillary model was digitally designed and milled. Twelve duplicated plaster casts were scanned and virtual denture bases designed accordingly. Physical complete denture bases (n = 12 per technique) were manufactured applying different digital and conventional fabrication methods: 1) CNC milling (MIL); 2) material jetting (MJ); 3) selective laser sintering (SLS); 4) digital light processing (DLP); and 5) conventional injection molding (INJ). The INJ group served as control. The intaglio surfaces of the denture bases were digitized and superposed with the surface data of the casts using a best-fit algorithm. Accuracy of surface adaptation was assessed by examining deviations. Statistical analysis was conducted using SPSS (P < 0.05). RESULTS: The milling of denture bases led to significantly better surface adaptation compared with all the other technologies (P < 0.001). The other fabrication methods in the study, including conventional manufacturing, revealed no considerable overall differences. CONCLUSIONS: As regards the accuracy of surface adaptation, all the investigated technologies adequately produced complete denture bases, with milled denture bases presenting the most superior results.

Prosthetic Management of Severe Mandibular Deviation in a Hemi-Mandibulectomy Patient Following Osteoradionecrosis.

Rehabilitation of a patient after hemi-mandibulectomy without reconstruction represents a prosthodontic challenge. Indeed, mandibular deviation and decreased occlusal contacts are a common presentation post-surgery. This paper reports on a patient who presented with these challenges and where chronic osteoradionecrosis has resulted in significant mandibular deviation. A maxillary cobalt chrome mandibular deviation device, designed with palatal bite plane and constructed using 3D printing methods, resulted in a successful outcome. The authors aim to show how restorative management of similar patients can be successful using a modern approach.

Selective Laser Sintering of a Photosensitive Drug: Impact of Processing and Formulation Parameters on Degradation, Solid State, and Quality of 3D-Printed Dosage Forms.

This research study utilized a light-sensitive drug, nifedipine (NFD), to understand the impact of processing parameters and formulation composition on drug degradation, crystallinity, and quality attributes (dimensions, hardness, disintegration time) of selective laser sintering (SLS)-based three-dimensional (3D)-printed dosage forms. Visible lasers with a wavelength around 455 nm are one of the laser sources used for selective laser sintering (SLS) processes, and some drugs such as nifedipine tend to absorb radiation at varying intensities around this wavelength. This phenomenon may lead to chemical degradation and solid-state transformation, which was assessed for nifedipine in formulations with varying amounts of vinyl pyrrolidone-vinyl acetate copolymer (Kollidon VA 64) and potassium aluminum silicate-based pearlescent pigment (Candurin) processed under different SLS conditions in the presented work. After preliminary screening, Candurin, surface temperature (ST), and laser speed (LS) were identified as the significant independent variables. Further, using the identified independent variables, a 17-run, randomized, Box-Behnken design was developed to understand the correlation trends and quantify the impact on degradation (%), crystallinity, and quality attributes (dimensions, hardness, disintegration time) employing qualitative and quantitative analytical tools. The design of experiments (DoEs) and statistical analysis observed that LS and Candurin (wt %) had a strong negative correlation on drug degradation, hardness, and weight, whereas ST had a strong positive correlation with drug degradation, amorphous conversion, and hardness of the 3D-printed dosage form. From this study, it can be concluded that formulation and processing parameters have a critical impact on stability and performance; hence, these parameters should be evaluated and optimized before exposing light-sensitive drugs to the SLS processes.

Selective laser sintering 3D printing - an overview of the technology and pharmaceutical applications.

Food and Drug Administration (FDA) has approved a drug product (Spritam®) and many medical devices manufactured by three-dimensional printing (3DP) processes for human use. There is immense potential to print personalized medicines using 3DP. Many 3DP methods have been reported in the literature for pharmaceutical applications. However, selective laser sintering (SLS) printing has remained least explored for pharmaceutical applications. There are many advantages and challenges in adopting a SLS method for fabrication of personalized medicines. Solvent-free nature, availability of FDA approved thermoplastic polymer/excipients (currently used in hot melt-extrusion process), minimal/no post-processing step, etc. are some of the advantages of the SLS printing process. Major challenges of the technology are requirement of at least one thermoplastic component in the formulation and thermal stability of drug and excipients. This review provides an overview of the SLS printing method, excipient requirements, process monitoring, quality defects, regulatory aspects, and potential pharmaceutical applications.

Formulation Optimization of Selective Laser Sintering 3D-Printed Tablets of Clindamycin Palmitate Hydrochloride by Response Surface Methodology.

The aims of the current study were to develop and evaluate clindamycin palmitate hydrochloride (CPH) 3D-printed tablets (printlets) manufactured by selective laser sintering (SLS). Optimization of the formulation was performed by studying the effect of formulation and process factors on critical quality attributes of the printlets. The independent factors studied were laser scanning speed, microcrystalline cellulose (MCC), and lactose monohydrate (LMH) concentration. The responses measured were printlets weight, hardness, disintegration time (DT), and dissolution in 30 min. The printlets were characterized for content uniformity, chemical interactions, crystallinity, drug distribution, morphology, and porosity. The laser scanning speed showed statistically significant effects on all the studied dependent responses (p < 0.05). MCC showed statistically significant effects on hardness, DT, and dissolution (p < 0.05), while LMH showed statistically significant effect on hardness and dissolution (p < 0.05). The model was validated by an independent formulation, and empirical values were in close agreement with model-predicted values. X-ray powder diffraction and differential scanning calorimetry data suggested a decrease in crystallinity of the LMH in the printlets. X-ray micro-CT scanning showed porous microstructure of the printlets with a porosity 24.4% and 31.1% for the printlets printed at 200 and 300 mm/s laser speed, respectively. In summary, the SLS method provides an opportunity to fabricate customized dosage forms as per patients' need.