University of Brasilia, School of Health Sciences, Laboratory of Food, Drugs and Cosmetics (LTMAC), 70.910-900, Brasília, DF, Brazil.
University of Brasilia, Faculty of Ceilandia, 72220-900, Brasília, DF, Brazil.
Eur J Pharm Sci. 2023 Sep 1;188:106517. doi: 10.1016/j.ejps.2023.106517. Epub 2023 Jul 3.
The in-situ formation of nanoparticles from polymer-based solid medicines, although previously described, has been overlooked despite its potential to interfere with oral drug bioavailability. Such polymeric pharmaceuticals are becoming increasingly common on the market and can become even more popular due to the dizzying advance of 3D printing medicines. Hence, this work aimed to study this phenomenon during the dissolution of 3D printed tablets produced with three different polymers, hydroxypropylmethylcellulose acetate succinate (HPMCAS), polyvinyl alcohol (PVA), and Eudragit RL PO® (EUD RL) combined with plasticizers and the model drug naringenin (NAR). The components' interaction, dissolution behavior, and characteristics of the formed particles were investigated employing thermal, spectroscopic, mechanical, and chromatographic assays. All the systems generated stable spherical-shaped particles throughout 24 h, encapsulating over 25% of NAR. Results suggest encapsulation efficiencies variations may depend on interactions between polymer-drug, drug-plasticizer, and polymer-plasticizer, which formed stable nanoparticles even in the drug absence, as observed with the HPMCAS and EUD RL formulations. Additionally, components solubility in the medium and previous formulation treatments are also a decisive factor for nanoparticle formation. In particular, the treatment provided by hot-melt extrusion and FDM 3D printing affected the dissolution efficiency enhancing the interaction between the components, reverberating on particle size and particle formation kinetics mainly for HPMCAS and EUD RL. In conclusion, the 3D printing process influences the in-situ formation of nanoparticles, which can directly affect oral drug bioavailability and needs to be monitored.
聚合物固体制剂中纳米粒子的原位形成，尽管之前已有描述，但由于其可能会影响口服药物生物利用度，因此一直被忽视。此类聚合物药物在市场上越来越常见，并且由于 3D 打印药物的飞速发展，它们可能会变得更加流行。因此，这项工作旨在研究在使用三种不同聚合物（羟丙甲纤维素醋酸琥珀酸酯（HPMCAS）、聚乙烯醇（PVA）和 Eudragit RL PO®（EUD RL））与增塑剂结合，并添加模型药物柚皮苷（NAR）的情况下，3D 打印片剂溶解过程中出现的这种现象。采用热分析、光谱分析、力学分析和色谱分析等方法研究了各成分之间的相互作用、溶解行为以及形成的颗粒特性。所有系统在 24 小时内均生成了稳定的球形颗粒，包封了超过 25%的 NAR。结果表明，包封效率的变化可能取决于药物与聚合物之间、药物与增塑剂之间以及聚合物与增塑剂之间的相互作用，正如 HPMCAS 和 EUD RL 制剂中观察到的那样，即使在缺乏药物的情况下，这些相互作用也会形成稳定的纳米颗粒。此外，各成分在介质中的溶解度和制剂前处理也是形成纳米颗粒的决定性因素。特别是热熔挤出和 FDM 3D 打印提供的处理会影响溶解效率，增强各成分之间的相互作用，从而主要对 HPMCAS 和 EUD RL 产生粒径和颗粒形成动力学的影响。总之，3D 打印工艺会影响纳米颗粒的原位形成，这可能会直接影响口服药物的生物利用度，因此需要进行监测。
