Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal 700054, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, West Bengal 700054, India.
Int J Pharm. 2024 Dec 25;667(Pt A):124881. doi: 10.1016/j.ijpharm.2024.124881. Epub 2024 Oct 28.
This research focuses on exploring the solid solubility and miscibility of Etoricoxib, a poorly water-soluble anti-inflammatory drug, within Soluplus®, a polymer used as a matrix for 3D-printed tablets. By utilizing hot-melt extrusion (HME), the drug was dispersed within Soluplus® to enhance its solubility. The extrudates were then employed in 3D printing to create customized solid oral dosage form. This study's novelty lies in combining HME and 3D printing, aiming to improve drug incorporation, stability, and effectiveness in the final formulation. Comprehensive characterization techniques, including hot stage microscopy (HSM), scanning electron microscopy (SEM), micro-computed tomography (Micro-CT), florescence microscopy, optical microscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), solubility studies, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and aqueous solubility study were utilized to elucidate the physicochemical properties, thermal stability, and structural integrity for the extruded filaments (the printing ink), and 3D printed tablets made thereof. Furthermore, the in vitro drug release profile of the 3D printed tablet was systematically evaluated, revealing a controlled drug release pattern from the finished dosage form. The systematic investigation reported herein, starting from theoretical miscibility to the printing ink development through HME, detailed characterization of the extruded filaments, and further solid oral formulation development by additive manufacturing can be utilized as a platform technology or a pathway for the development of personalized medicine with drugs having similar physicochemical properties.
本研究聚焦于探索依托考昔(一种水溶性较差的抗炎药)在 Soluplus®(一种用于 3D 打印片剂基质的聚合物)中的固溶度和混溶性。通过利用热熔挤出(HME),将药物分散在 Soluplus®中以提高其溶解度。然后将挤出物用于 3D 打印以创建定制的固体口服剂型。本研究的新颖之处在于结合 HME 和 3D 打印,旨在提高药物在最终配方中的掺入率、稳定性和效果。综合的表征技术,包括热台显微镜(HSM)、扫描电子显微镜(SEM)、微计算机断层扫描(Micro-CT)、荧光显微镜、光学显微镜、X 射线衍射(XRD)、傅里叶变换红外光谱(FT-IR)、溶解度研究、差示扫描量热法(DSC)、热重分析(TGA)和水溶解度研究,用于阐明挤出丝(印刷油墨)的物理化学性质、热稳定性和结构完整性,以及由此制成的 3D 打印片剂。此外,系统地评估了 3D 打印片剂的体外药物释放曲线,揭示了从最终剂型中呈现出的控释药物释放模式。本文从理论上的混合溶解度开始,通过 HME 开发打印油墨,对挤出丝进行详细的表征,以及通过添加剂制造进一步开发固体口服制剂,所报道的系统研究可以用作平台技术或具有类似物理化学性质的药物的个性化医疗发展的途径。