da Costa Nuno F, Azevedo Raquel F, Lopes João A, Fernandes Ana I, Pinto João F
iMed.ULisboa-Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
CiiEM-Interdisciplinary Research Center Egas Moniz, Instituto Universitário Egas Moniz, Monte de Caparica, 2829-511 Caparica, Portugal.
Pharmaceutics. 2022 Nov 24;14(12):2587. doi: 10.3390/pharmaceutics14122587.
In situ amorphization is a promising approach, considered in the present work, to enhance the solubility and dissolution rate of olanzapine, while minimizing the exposure of the amorphous material to the stress conditions applied during conventional processing. The production of pellets by extrusion/spheronization and the coating of inert beads were investigated as novel methods to promote the co-amorphization of olanzapine, a poorly water-soluble drug, and saccharin. Samples were characterized using differential scanning calorimetry, X-ray powder diffraction, Fourier-transform infrared spectroscopy and scanning electron microscopy, and dissolution and stability testing. The co-amorphous produced were compared with crystalline olanzapine, or physical mixture of olanzapine and saccharin. Results suggested that the addition of water to mixtures containing olanzapine and saccharin during the production of pellets, and the coating of inert beads, induced the in situ co-amorphization of these substances. The coating of inert beads enhanced the solubility and dissolution rate of olanzapine, especially when compared to pellets coated with the crystalline drug, but also with pellets containing the co-amorphous entity in the matrix of beads. Nine months stability tests (23 °C/60% RH) confirmed the preservation of the solid-state properties of the co-amorphous form on/in pellets. Overall, results highlighted the feasibility and benefits of in situ co-amorphization, either when the drug was entrapped in the pellets matrix, or preferentially applied directly on the surface of pellets.
原位非晶化是一种很有前景的方法,在本研究中被考虑用于提高奥氮平的溶解度和溶出速率,同时将非晶态材料在传统加工过程中所受的应力条件影响降至最低。研究了通过挤出/滚圆法制备微丸以及对惰性珠粒进行包衣,作为促进难溶性药物奥氮平和糖精共非晶化的新方法。使用差示扫描量热法、X射线粉末衍射、傅里叶变换红外光谱和扫描电子显微镜对样品进行表征,并进行溶出度和稳定性测试。将制备的共非晶态产物与结晶奥氮平或奥氮平和糖精的物理混合物进行比较。结果表明,在微丸生产过程中向含有奥氮平和糖精的混合物中加水以及对惰性珠粒进行包衣,可诱导这些物质的原位共非晶化。惰性珠粒包衣提高了奥氮平的溶解度和溶出速率,特别是与用结晶药物包衣的微丸相比,也与在珠粒基质中含有共非晶态实体的微丸相比。九个月的稳定性试验(23℃/60%相对湿度)证实了共非晶态形式在微丸上/中的固态性质得以保留。总体而言,结果突出了原位共非晶化的可行性和益处,无论是药物被包封在微丸基质中,还是优先直接应用于微丸表面。