Use of Three-Dimensional Printing Techniques in the Management of a Patient Suffering From Traumatic Loss of the Talus

Traumatic loss of the whole talus is extremely rare, and its possible treatment options are limited. Our experience of treatment of a 30-year-old male suffering from traumatic loss of the whole talus with the insertion of an anatomical antibiotic-loaded talus cement spacer using 3-dimensional printing techniques as an interim measure was reviewed and reported. A young motorcyclist was brought to the emergency department after a road traffic accident. He sustained multiple injuries including traumatic loss of his left talus. Despite repeated surgeries of debridement and insertion of external fixator to his injured ankle, the patient had residual problem of ankle instability, ankle infection, and absence of his involved talus. With the help of computerized 3-dimensional printing techniques, an anatomical talus cement spacer was produced in the operating room and inserted into the patient's ankle 7 weeks after the initial trauma. The external fixator was kept for another 3 weeks before removal. At 14 months after the insertion of cement spacer, the patient could walk independently without any pain for 15 minutes with the help of a crutch occasionally. However, the range of motion of his left ankle was limited to 15° in the flexion-extension arc and minimal subtalar motion. The infection of the left ankle was under control.     

In vitro dissolution and oral bioavailability study of fenofibrate nanomatrix system prepared by hot-melt extrusion

Solvent evaporation method for preparation of nanomatrix has the disadvantages, such as residual organic solvent, environmental pollution, explosion-proofing and so on. To overcome these shortcomings, a series of fenofibrate nanomatrix drug delivery system (NDDS) consisting of nano-porous silica Sylysia^®350 (S350) and pH sensitive material Eudragit^® L100-55 (EL100-55) were prepared using hot-melt extrusion (HME), and their in vitro dissolution and in vivo bioavailability were compared. Finally, the formulation with the highest in vivo bioavailability was selected as the optimized formulation for DSC and PXRD characterization. The results showed that the optimized NDDS showed a higher bioavailability than the reference formulation, although there was crystalline form drug remaining in NDDS. The relative bioavailability of the optimized formulation was 157.1% compared with the commercial product Lipanthyl^®. In addition, the relative bioavailability of the optimized formulation was 124.8% in comparison with the formulation prepared by solvent evaporation method, showing that the NDDS prepared by the HME method was effective in improving the bioavailability of fenofibrate. In conclusion, HME was a promising method to prepare NDDS.     

Ultrasound-Assist Extrusion Methods for the Fabrication of Polymer Nanocomposites Based on Polypropylene/Multi-Wall Carbon Nanotubes

Isotactic polypropylenes (iPP) with different melt flow indexes (MFI) were used to fabricate nanocomposites (NCs) with 10 wt % loadings of multi-wall carbon nanotubes (MWCNTs) using ultrasound-assisted extrusion methods to determine their effect on the morphology, melt flow, and electrical properties of the NCs. Three different types of iPPs were used with MFIs of 2.5, 34 and 1200 g/10 min. Four different NC fabrication methods based on melt extrusion were used. In the first method melt extrusion fabrication without ultrasound assistance was used. In the second and third methods, an ultrasound probe attached to a hot chamber located at the exit of the die was used to subject the sample to fixed frequency and variable frequency, respectively. The fourth method is similar to the first method, with the difference being that the carbon nanotubes were treated in a fluidized air-bed with an ultrasound probe before being used in the fabrication of the NCs with no ultrasound assistance during extrusion. The samples were characterized by MFI, Optical microscopy (OM), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), electrical surface resistivity, and electric charge. MFI decreases in all cases with addition of MWCNTs with the largest decrease observed for samples with the highest MFI. The surface resistivity, which ranged from 10¹³ to 10⁵ Ω/sq, and electric charge, were observed to depend on the ultrasound-assisted fabrication method as well as on the melt flow index of the iPP. A relationship between agglomerate size and area ratio with electric charge was found. Several trends in the overall data were identified and are discussed in terms of MFI and the different fabrication methods.     

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I

Introduction: Currently, hot melt extrusion (HME) is a promising technology in the pharmaceutical industry, as evidenced by its application to manufacture various FDA-approved commercial products in the market. HME is extensively researched for enhancing the solubility and bioavailability of poor water-soluble drugs, taste masking, and modifying release in drug delivery systems. Additionally, its other novel opportunities or pharmaceutical applications, and capability for continuous manufacturing are being investigated. This efficient, industrially scalable, solvent-free, continuous process can be easily automated and coupled with other novel platforms for continuous manufacturing of pharmaceutical products.

Areas covered: This review focuses on updates on solubility enhancement of poorly water-soluble drugs and process analytical tools such as UV/visible spectrophotometry; near-infrared spectroscopy; Raman spectroscopy; and rheometry for continuous manufacturing, with a special emphasis on fused deposition modeling 3D printing.

Expert opinion: The strengths, weakness, opportunities, threats (SWOT) and availability of commercial products confirmed wide HME applicability in pharmaceutical research. Increased interest in continuous manufacturing processes makes HME a promising strategy for this application. However, there is a need for extensive research using process analytical tools to establish HME as a dependable continuous manufacturing process.     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

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??Objective    To evaluate and compare the amount of debris and irrigant extrusion quantitatively by using rotary nickel-titanium ??Ni-Ti?? instrument and sonic handpiece in root canal preparation. Methods    Forty freshly extracted human teeth were selected??which were with single canals??having similar canal length and curvature??due to orthodontics therapy and periodontitis in Department of Oral and Maxillofacial Surgery of China Medical University Stomatology Hospital during October 2012 to January 2014. They were separated into two groups based on Ni-Ti instruments ProTaper and sonic handpiece and mounted in a debris collection apparatus. After each instrument change??1 mL of NaClO was used as the irrigant and the amount of irrigant extruded was measured by EP tube. The EP tube was weighed using an electronic microbalance to determine its weight. After drying in an incubator for five days??the EP tube was weighed again. Compare the amount of debris and irrigant extrusion quantitatively. Results    The median of the amount of irrigant??in the group of ProTaper it was 116.24 mg??in the group of sonic handpiece it was 13.76 mg. The rotary Ni-Ti instrumentation techniques extruded significantly more irrigant than sonic handpiece??P < 0.05??. The median of the amount of debris??in the group of ProTaper it was 4.87 mg??in the group of sonic handpiece it was 0.63 mg. The rotary Ni-Ti instrumentation techniques extruded significantly more debris than sonic handpiece??P < 0.05??. Conclusion    The sonic handpiece extrudes significantly less irrigant and debris than the rotary Ni-Ti instrumentation techniques. It has a good clinical application prospects.     

Piezosurgical management of sealer extrusion‐associated mental nerve anaesthesia: A case report

The present report describes a case where sealer extrusion (Sealapex) occurred during root canal obturation of a left lower second premolar tooth, and the patient experienced sudden pain and followed by complete anaesthesia of the lower lip. After 3 weeks of conservative therapy and an unaltered anaesthesia period, piezosurgical removal of the extruded sealer and root‐end resection was performed despite the direct contact with the mental neurovascular bundle. At suture removal, 1 week after surgery, there was no improvement in sensation. Two weeks after the operation, the patient reported some changes, including a short paraesthesia period alternating with anaesthesia. At the fourth post‐operative week, neurosensory function recovered completely. This case represents successful use of the piezoelectric technique for mental nerve decompression and periapical surgery of a lower second premolar with close contact of the mental nerve.     

Preoperative morphologic changes of the medial meniscus correlate with suture translations during knee flexion in pullout repair of medial meniscus posterior root tear

BackgroundMedial meniscus (MM) translates and extrudes posteriorly during knee flexion in MM posterior root tear (MMPRT) knees, and transtibial pullout repair of MMPRT has been performed to regulate the MM extrusion. This study aimed to calculate each suture translation during knee flexion in transtibial pullout repair of MMPRT, and to investigate the morphologic features of the MM that lead to longer suture translations during knee flexion.MethodsThirty patients with MMPRT who met the operative indication of pullout repair were enrolled and investigated prospectively. Pullout repair was performed by using two simple stitches (outer and inner sutures) and an all-inside suture in the posteromedial part of the MM. Each suture’s translation from 0° to 90° of knee flexion was measured intraoperatively. The MM morphologic features, including MM medial extrusion (MMME) and MM posterior height (MMPH), were measured using preoperative magnetic resonance imaging, and the correlation between these values and each suture translation was evaluated.ResultsThe average outer, inner, and all-inside suture translations were 4.8 mm, 3.9 mm, and 1.3 mm, respectively. Significant correlations were observed between the outer suture translation and MMME, and MMPH (p < 0.001 and <0.01, respectively). The thresholds for preoperative MMME and MMPH for longer outer suture translations (≥6 mm) were 2.1 mm and 5.4 mm, respectively.ConclusionsPreoperative longer MMME and higher MMPH were associated with longer meniscus translations during knee flexion during MMPRT repair.