DEVELOPMENT OF SITE - SPECIFIC DRUG DELIVERY SYSTEMS USING HOT MELT EXTRUSION AND FUSED DEPOSITION MODELING 3D PRINTING

Due to preferential site of drug absorption and the need for increased concentration of medication at the required tissues, dosage forms should be designed or formulated in such a way that medication is released at a specific site or after a specific time in the gastrointestinal tract (GIT). Knowledge of transit times of dosage forms in each part of GIT, by use of particular polymers or employing specific delivery systems such as floating systems, delivery of medication to specific sites in the GIT can be achieved. HME coupled FDM 3D printing has the capability to create customized dosage forms for personalized pharmacotherapy with its ability to produce dosage forms with complex structures, customized shapes, and sizes. Chronotherapy deals with synchronizing drug delivery with the body’s circadian rhythm to optimize therapeutic efficacy and minimize side effects. Using the advantage of pH-dependent solubility of Eudragit S100 (ES100) (as an enteric polymer that solubilizes and releases the drug at above pH 7), a chronotherapeutic drug delivery system for KTP and IBU was successfully developed for the treatment of arthritis conditions in the early morning hours. The drug release studies conducted in different media showed the desired lag time and release characteristics. Maintaining a constant plasma drug concentration is not beneficial in all disease conditions. Some diseases may require pulse delivery of drugs to avoid unwanted adverse effects and drug exposure. Various biological factors influence the transit time of drugs in the upper gastrointestinal tract and possess a challenge to the drugs that are locally active in the stomach, unstable at a high pH, or poorly soluble in the lower parts of the gastrointestinal tract. To overcome these issues, a floating pulsatile system was developed which showed a high potential to deliver drugs that need high residence time in the stomach and the pulsatile release of theophylline. Quality by design (QbD) is defined as a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding based on sound science and quality risk management. QbD is combined with FDM 3D printing to develop personalized dosage forms for patient-centric pharmacotherapy

Novel gastroretentive floating pulsatile drug delivery system produced via hot-melt extrusion and fused deposition modeling 3D printing

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This study was performed to develop novel core-shell gastroretentive floating pulsatile drug delivery systems using a hot-melt extrusion-paired fused deposition modeling (FDM) 3D printing and direct compression method. Hydroxypropyl cellulose (HPC) and ethyl cellulose (EC)-based filaments were fabricated using hot-melt extrusion technology and were utilized as feedstock material for printing shells in FDM 3D printing. The directly compressed theophylline tablet was used as the core. The tablet shell to form pulsatile floating dosage forms with different geometries (shell thickness: 0.8, 1.2, 1.6, and 2.0 mm; wall thickness: 0, 0.8, and 1.6 mm; and % infill density: 50, 75, and 100) were designed, printed, and evaluated. All core-shell tablets floated without any lag time and exhibited good floating behavior throughout the dissolution study. The lag time for the pulsatile release of the drug was 30 min to 6 h. The proportion of ethyl cellulose in the filament composition had a significant (p \u3c 0.05) effect on the lag time. The formulation (2 mm shell thickness, 1.6 mm wall thickness, 100% infill density, 0.5% EC) with the desired lag time of 6 h was selected as an optimized formulation. Thus, FDM 3D printing is a potential technique for the development of complex customized drug delivery systems for personalized pharmacotherapy

Reciprocal Changes in Sagittal Alignment in Adolescent Idiopathic Scoliosis Patients Following Strategic Pedicle Screw Fixation

Study DesignRetrospective observational study.PurposeTo analyze the effect of low-density (LD) strategic pedicle screw fixation on the correction of coronal and sagittal parameters in adolescent idiopathic scoliosis (AIS) patients.Overview of LiteratureLD screw fixation achieves favorable coronal correction, but its effect on sagittal parameters is not well established. AIS is often associated with decreased thoracic kyphosis (TK), and the use of multi-level pedicle screws may result in further flattening of the sagittal profile.MethodsA retrospective analysis was performed on 92 patients with AIS to compare coronal and sagittal parameters preoperatively and at 2-year follow-up. All patients underwent posterior correction via LD strategic pedicle screw fixation. Radiographs were analyzed for primary Cobb angle (PCA), coronal imbalance, cervical sagittal angle (CSA), TK, lumbar lordosis (LL), pelvic incidence, pelvic tilt (PT), sacral slope (SS), C7 plumb line, spino-sacral angle, curve flexibility, and screw density.ResultsPCA changed significantly from 57.6°±13.9° to 19°±8.4° (p 40°) showed significant correction of TK (p <0.0001 in both). Sacro-pelvic parameters showed a significant decrease of PT and increase of SS, suggesting a reduction in pelvic retroversion SS (from 37° to 40°, p =0.0001) and PT (from 15° to 14°, p =0.025).ConclusionsLD strategic pedicle screw fixation provides favorable coronal correction and improves overall sagittal sacro-pelvic parameters. This technique does not cause significant flattening of TK and results in a favorable restoration of TK in patients with hypokyphosis or hyperkyphosis

Novel Gastroretentive Floating Pulsatile Drug Delivery System Produced via Hot-Melt Extrusion and Fused Deposition Modeling 3D Printing

This study was performed to develop novel core-shell gastroretentive floating pulsatile drug delivery systems using a hot-melt extrusion-paired fused deposition modeling (FDM) 3D printing and direct compression method. Hydroxypropyl cellulose (HPC) and ethyl cellulose (EC)-based filaments were fabricated using hot-melt extrusion technology and were utilized as feedstock material for printing shells in FDM 3D printing. The directly compressed theophylline tablet was used as the core. The tablet shell to form pulsatile floating dosage forms with different geometries (shell thickness: 0.8, 1.2, 1.6, and 2.0 mm; wall thickness: 0, 0.8, and 1.6 mm; and % infill density: 50, 75, and 100) were designed, printed, and evaluated. All core-shell tablets floated without any lag time and exhibited good floating behavior throughout the dissolution study. The lag time for the pulsatile release of the drug was 30 min to 6 h. The proportion of ethyl cellulose in the filament composition had a significant (p &lt; 0.05) effect on the lag time. The formulation (2 mm shell thickness, 1.6 mm wall thickness, 100% infill density, 0.5% EC) with the desired lag time of 6 h was selected as an optimized formulation. Thus, FDM 3D printing is a potential technique for the development of complex customized drug delivery systems for personalized pharmacotherapy

Controlling drug release with additive manufacturing-based solutions

3D printing is an innovative manufacturing technology with great potential to revolutionise solid dosage forms. Novel features of 3D printing technology confer advantage over conventional solid dosage form manufacturing technologies, including rapid prototyping and an unparalleled capability to fabricate complex geometries with spatially separated conformations. Such a novel technology could transform the pharmaceutical industry, enabling the production of highly personalised dosage forms with well-defined release profiles. In this work, we review the current state of the art of using additive manufacturing for predicting and understanding drug release from 3D printed novel structures. Furthermore, we describe a wide spectrum of 3D printing technologies, materials, procedure, and processing parameters used to fabricate fundamentally different matrices with different drug releases. The different methods to manipulate drug release patterns including the surface area-to-mass ratio, infill pattern, geometry, and composition, are critically evaluated. Moreover, the drug release mechanisms and mathematical models that could aid exploiting the release profile are also covered. Finally, this review also covers the design opportunities alongside the technical and regulatory challenges that these rapidly evolving technologies present. [Abstract copyright: Copyright © 2021. Published by Elsevier B.V.