July 22, 2020 by admin 0 Comments

Orodispersible Polymer Films with the Poorly Water-Soluble Drug, Olanzapine: Hot-Melt Pneumatic Extrusion for Single-Process 3D Printing

Authors
Hui-Won Cho 1, Seung-Hoon Baek 1, Beom-Jin Lee 1 and Hyo-Eon Jin 1,2,*
Abstract
Amorphous solid dispersions (ASDs) improve the oral delivery of poorly water-soluble drugs. ASDs of olanzapine (OLZ), which have a high melting point and low solubility, are performed using a complicated process. Three-dimensional (3D) printing based on hot-melt pneumatic extrusion (HMPE) is a simplified method for producing ASDs. Unlike general 3D printing, printlet extrusion is possible without the preparation of drug-loaded filaments. By heating powder blends, direct fused deposition modeling (FDM) printing through a nozzle is possible, and this step produces ASDs of drugs. In this study, we developed orodispersible films (ODFs) loaded with OLZ as a poorly water-soluble drug. Various ratios of film-forming polymers and plasticizers were investigated to enhance the printability and optimize the printing temperature. Scanning electron microscopy (SEM) showed the surface morphology of the film for the optimization of the polymer carrier ratios. Differential scanning calorimetry (DSC) was used to evaluate thermal properties. Powder X-ray diffraction (PXRD) confirmed the physical form of the drug during printing. The 3D printed ODF formulations successfully loaded ASDs of OLZ using HMPE. Our ODFs showed fast disintegration patterns within 22 s, and rapidly dissolved and reached up to 88% dissolution within 5 min in the dissolution test. ODFs fabricated using HMPE in a single process of 3D printing increased the dissolution rates of the poorly water-soluble drug, which could be a suitable formulation for fast drug absorption. Moreover, this new technology showed prompt fabrication feasibility of various formulations and ASD formation of poorly water-soluble drugs as a single process. The immediate dissolution within a few minutes of ODFs with OLZ, an atypical antipsychotic, is preferred for drug compliance and administration convenience.

June 30, 2020 by admin 0 Comments

Preparation and evaluation of identifiable quick response (QR)-coded orodispersible films using 3D printer with directly feeding nozzle

Authors
Byung-Cheol Oh (a), Gang Jin (a), Chulhun Park (b), Jun-Bom Park (c), Beom-Jin Lee (a),(d)
Abstract
3D-printing technology is growing in importance due to increased availability and a wider range of applications. Here, we prepared and evaluated a hot melt pneumatic (HMP) 3D-printed QR (Quick Response)-coded orodispersible film (QRODF) containing a poorly water-soluble aripiprazole (ARP). Moreover, QRODF was formulated to evaluate the extrusion process and characterize physicochemical properties of drug-loaded films. QRODF was designed with a 30-mm length/width and 0.3-mm thickness by varying QRODF formulations with different polyethylene oxide 100,000(PEO)/poloxamer 188(POX188) ratios and then optimized for extrusion accessibility and film-forming capability. The optimal QRODF formulation was further controlled by ARP and citric acid addition (pH control) for salivary applicability and dissolution rate. Physicochemical evaluation of QRODF was performed by scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. Dissolution studies were performed in buffer media (pH 1.2) following USP Apparatus type II method. Drug-loaded QRODF was scannable using a smartphone. Drug release from QRODF rapidly reached over 95% and was dependent on polymer/poloxamer ratios. By optimizing PEO/POX/drug ratio, the morphology and physical properties of the oral film were changed. Furthermore, disintegration and dissolution rates of ARP-loaded QRODF were successfully established in a controlled manner.

June 10, 2020 by admin 0 Comments

pH-dependent nanodiamonds enhance the mechanical properties of 3D-printed hyaluronic acid nanocomposite hydrogels

Authors
Dae Gon Lim, Eunah Kang & Seong Hoon Jeong
Abstract
Nanocomposite hydrogels capable of undergoing manufacturing process have recently attracted attention in biomedical applications due to their desired mechanical properties and high functionality. 3D printing nanocomposite hydrogels of hyaluronic acid (HA)/nanodiamond (ND) revealed that the addition of ND with the low weight ratio of 0.02 wt% resulted in higher compressive force and gel breaking point, compared with HA only nanocomposites. These HA nanocomposite hydrogels loaded with surface functionalized ND allowed for the enforced compressive stress to be tuned in a pH-dependent manner. HA nanocomposite hydrogels with ND-OH at pH 8 showed an increase of 1.40-fold (0.02%: 236.18 kPa) and 1.37-fold (0.04%: 616.72 kPa) the compressive stress at the composition of 0.02 wt% and 0.04 wt, respectively, compared to those of ND-COOH (0.02%: 168.31 kPa, 0.04%: 449.59 kPa) at the same pH. Moreover, the compressive stress of HA/ND-OH (0.04 wt%) at pH 8 was mechanically enhanced 1.29-fold, compared to that of HA/ND-OH (0.04 wt%) at pH 7. These results indicate that the tunable buffering environment and interaction with the long chains of HA at the molecular level have a critical role in the dependency of the mechanical properties on pH. Due to the pH stability of the ND-OH nanophase, filament-based processing and layer-based deposition at microscale attained enforced mechanical properties of hydrogel. Fine surface tuning of the inorganic ND nanophase and controlled 3D printing leads to improved control over the pH-dependent mechanical properties of the nanocomposite hydrogels reported herein.