3-Dimensional printing (3DP) constitutes a raft of technologies, based on different physical mechanisms, that generate a 3-dimensional physical object from a digital model. Because of its rapid fabrication and precise geometry, 3DP has gained a prominent focus in biomedical and nanobiomaterials research. Despite advancements in targeted, controlled, and pulsatile drug delivery, the achievement of site-specific and disease-responsive drug release and stringent control over in vivo biodistribution, are still some of the important, challenging areas for pharmaceutical research and development and existing drug delivery techniques. Microelectronic industries are capable of generating nano-/microdrug delivery devices at high throughputs with a highly precise control over design. Successful miniaturizations of micro-pumps with multireservoir architectures for delivery of pharmaceuticals developed by micro-electromechanical systems technology were more acceptable than implantable devices. Inkjet printing technologies, which dispense a precise amount of polymer ink solutions, find applications in controlled drug delivery. Bioelectronic products have revolutionized drug delivery technologies. Designing nanoparticles by nanoimprint lithography showed a controlled drug release pattern, biodistribution, and in vivo transport. This review highlights the "top-down" and "bottom-up" approaches of the most promising 3DP technologies and their broader applications in biomedical and therapeutic drug delivery, with critical assessment of its merits, demerits, and intellectual property rights challenges.

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A bioequivalence study was proved of generic Febuxostat 80 mg tablets (T) in healthy volunteers.For this purpose, Authors developed a simple, sensitive, selective, rapid, rugged and reproducible liquid chromatography–tandem mass spectrometry method for the quantification of Febuxostat (FB) in human plasma using Febuxostat D7 (FBD7) as an internal standard (IS) was used. Chromatographic separation was performed on Ascentis Express C18 (50x4.6 mm, 3.5 μ) column. Mobile phase composed of 10 mM Ammonium formate: Acetonitrile (20:80 v/v), with 0.8 mL/min flow-rate. Drug and IS were extracted by Liquid- liquid extraction. FB and FBD7 were detected with proton adducts at m/z 317.1→261.1 and 324.2→262.1 in multiple reaction monitoring (MRM) positive mode respectively. The method was validated with the correlation coefficients of (r2) ≥ 0.9850 over a linear concentration range of 1.00-8000.00 ng/mL. This method demonstrated intra and inter-day precision within 2.64 to 3.88 and 2.76 to 8.44% and accuracy within 97.33 to 99.05 and 100.30 to 103.19% for FB. This method is successfully applied in the Bioequivalence study of 9 human volunteers.

A simple, sensitive and specific liquid chromatography–tandem mass spectrometry method was developed for simultaneous quantification of ezetimibe and simvastatin in rat plasma. The deuterium isotopes: ezetimibe d4 and simvastatin d6 were used as internal standards for ezetimibe and simvastatin, respectively. MS/MS detection involved a switch of electron spray ionization mode from negative to positive at retention time 3.01 min. Samples were extracted from plasma by liquid–liquid extraction using tertiary butyl methyl ether. Chromatographic separation was achieved with Agilent Eclipse XBD-C18 column using mobile phase that consisted of a mixture of ammonium acetate (pH4.5; 10 mM)–acetonitrile (25:75 v/v). The method was linear and validated over the concentration range of 0.2–40.0 ng/mL for simvastatin and 0.05–15.0 ng/mL for ezetimibe. The transitions selected were m/z 408.3→271.1 and m/z 412.0→275.10 for ezetimibe and ezetimibe d4, and m/z 419.30→285.20 and m/z 425.40→199.20 for simvastatin and simvastatin d6. Intra- and inter-batch precisions for ezetimibe were 1.6–14.8% and 2.1–13.4%; and for simvastatin 0.94–9.56% and 0.79–12%, respectively. The proposed method was sensitive, selective, precise and accurate for the quantification of ezetimibe and simvastatin simultaneously in rat plasma. The method was successfully applied to a pharmacokinetic study by oral co-administration of ezetimibe and simvastatin in SD rats.

A simple, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the quantification of milnacipran (MC) in rat plasma by using the liquid–liquid extraction method. Milnacipran-d10 (MCD10) was used as an internal standard (IS). Chromatographic separation was achieved on Zorbax SB-CN (4.6 mm×75 mm, 3.5 µm) column with an isocratic mobile phase composed of 10 mM ammonium acetate (pH 4.0) and methanol in the ratio of 25:75(v/v), at a flow-rate of 0.7 mL/min. MC and MCD10 were detected with proton adducts at m/z 247.2→230.3 and m/z 257.2→240.4 in multiple reaction monitoring (MRM) positive mode respectively. The method was validated over a linear concentration range of 1.00–400.00 ng/mL with a correlation coefficient (r2)≥0.9850. This method demonstrated intra- and inter-day precision within 5.40–10.85% and 4.40–8.29% and accuracy within 97.00–104.20% and 101.64–106.23%. MC was found to be stable throughout three freeze–thaw cycles, bench top and postoperative stability studies. This method was successfully applied to a pharmacokinetic study of rats through i.v. administration.

The objective was to investigate the antiurolithiatic activity of aqueous plant extract of Melia azadirachta using the zinc disc implantation model in male Wistar albino rats. A significant increase in urinary excretion of calcium, oxalate, magnesium and phosphate was observed after four weeks of implantation of zinc discs. After treatment with aqueous extract of Melia azadirachta caused a significant reduction (p < 0.001) in stone weight and urinary excretion of electrolytes in both the preventive and curative group of animals as compared to those of control groups. This explains the effect of the aqueous extract of Melia azadirachta in preventing urolithiasis (59%) and dissolving the pre-formed magnesium ammonium phosphate type of stones (46%). The possible mechanism could be due to the urinary stone-formation, lowering, antioxidant, diuretic, nephroprotective constituents present in Melia azadirachta. These results suggest the usefulness of aqueous plant extract of Melia azadirachta as an antiurolithiatic agent.

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