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.

Effect of a 2-HP-ß-Cyclodextrin Formulation on the Biological Transport and Delivery of Chemotherapeutic PLGA Nanoparticles.

BACKGROUND: The aim of this work was to develop a novel and feasible modification strategy by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-ß-CD) for enhancing the biological transport efficiency of paclitaxel (PTX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles. METHODS: PTX-loaded 2-HP-ß-CD-modified PLGA nanoparticles (2-HP-ß-CD/PLGA NPs) were prepared using the modified emulsion method. Nano-characteristics, drug release behavior, in vitro cytotoxicity, cellular uptake profiles and in vivo bio-behavior of the nanoparticles were then characterized. RESULTS: Compared with the plain PLGA NPs, 2-HP-ß-CD/PLGA NPs exhibited smaller particle sizes (151.03±1.36 nm), increased entrapment efficiency (~49.12% increase) and sustained drug release. When added to A549 human lung cancer cells, compared with PLGA NPs, 2-HP-ß-CD/PLGA NPs exhibited higher cytotoxicity in MTT assays and improved cellular uptake efficiency. Pharmacokinetic analysis showed that the AUC value of 2-HP-ß-CD/PLGA NPs was 2.4-fold higher than commercial Taxol® and 1.7-fold higher than plain PLGA NPs. In biodistribution assays, 2-HP-ß-CD/PLGA NPs exhibited excellent stability in the circulation. CONCLUSION: The results of this study suggest that the formulation that contains 2-HP-ß-CD can prolong PTX release, enhance drug transport efficiency and serve as a potential tumor targeting system for PTX.

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.