Laboratório de Farmacotécnica Experimental, Instituto de Tecnologia em Fármacos (Famanguinhos), FIOCRUZ, Rua Sizenando Nabuco 100 - Manguinhos., Rio de Janeiro, RJ, Brazil.
Seção de Análise e Identificação de Compostos com Potencial Terapêutico, Instituto de Tecnologia em Fármacos (Farmanguinhos), FIOCRUZ, Rio de Janeiro, RJ, Brazil.
AAPS PharmSciTech. 2022 Feb 2;23(2):69. doi: 10.1208/s12249-022-02219-7.
In this study, chloroquine resinates were prepared at a 1:1 (w:w) drug-to-resin ratio using the batch method with polacrilex (PC), sodium polystyrene sulfonate (SPS), and polacrilin potassium (PP) ion exchange resins (IER). The influence of drug/resin ratio and pH of the medium on drug loading efficiency was explored. UV-VIS spectrophotometric analysis showed that SPS resin had high loading efficiency for chloroquine diphosphate (CLP), above 89%, regardless of the pH. PP resin was more effective at pH 5.0 (90.68%) than at pH 1.0 (2.09%), and PC resin had only 27.63% of CLP loading efficiency. CLP complexation with IER yielded amorphous mixtures according to results from differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD), thus indicating drug-resin interaction. The taste masking efficiency was evaluated with in vitro methods using an adapted dissolution test and an electronic tongue system. During dissolution tests, SPS released only 1.0% of CLP after 300 s, while PP released over 10% after 90 s in simulated saliva solution. The electronic tongue distinguished the samples containing CLP, resins, and resinates by using multidimensional projection techniques that indicated an effective drug taste masking. In an accelerated stability study, the drug contents did not decrease in chloroquine resinates, and there was no physical degradation of the resinates after 60 days. Using chloroquine resinates therefore represents a novel way to evaluate taste masking in vitro which is relevant for the early formulation development process.
在这项研究中，采用批处理法，以聚卡瑞林（PC）、聚苯乙烯磺酸钠（SPS）和聚丙烯酸树脂钾（PP）离子交换树脂（IER）为基质，制备了药物与基质比例为 1:1（w:w）的氯喹树脂酸盐。考察了药物/树脂比和介质 pH 对药物载药效率的影响。紫外可见分光光度分析表明，SPS 树脂对磷酸氯喹（CLP）的负载效率较高，无论 pH 值如何，均高于 89%。PP 树脂在 pH 5.0 时（90.68%）比在 pH 1.0 时（2.09%）更有效，而 PC 树脂的 CLP 负载效率仅为 27.63%。根据差示扫描量热法（DSC）和 X 射线粉末衍射（XRPD）的结果，CLP 与 IER 的络合生成无定形混合物，表明药物与树脂之间存在相互作用。采用改良的溶出度试验和电子舌系统，通过体外方法评估了掩味效率。在溶出度试验中，SPS 在模拟唾液溶液中 300 s 后仅释放了 1.0%的 CLP，而 PP 在 90 s 后释放了超过 10%的 CLP。电子舌通过使用多维投影技术区分了含有 CLP、树脂和树脂酸盐的样品，表明药物的味道得到了有效掩蔽。在加速稳定性研究中，氯喹树脂酸盐中的药物含量没有下降，并且在 60 天后，树脂酸盐没有发生物理降解。因此，使用氯喹树脂酸盐代表了一种新的体外掩味评价方法，这对于早期制剂开发过程具有重要意义。
