Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
Drug Dev Ind Pharm. 2009 Dec;35(12):1409-18. doi: 10.3109/03639040902939247.
The purpose of this work was to investigate the effect of preparation methods and the drug-to-resin ratio on complex formation between risperidone and amberlite resin.
The existence of such resin complex may provide taste-masking properties to the dosage forms. It is important to determine when and how the complex forms. Therefore, in this study, the complexes of risperidone and amberlite resin were prepared by granulation, solution, and freeze-drying methods at various drug-to-resin ratios. The physical mixtures of drug-resin were used to compare the results of complexes prepared by granulation, solution, and freeze drying. The complexes were evaluated by various methods of characterization including differential scanning calorimetry, X-ray diffraction, spectroscopy (near infrared, Fourier transform infrared, and Raman), drug release, and binding studies.
Complexation between risperidone and amberlite was investigated for various preparation methods. It was found that complexation occurred at lower amounts of amberlite resin (drug-to-resin ratios of 1:1 and 1:2) when solution form of drug was contacted with the resin as in the case of solution and freeze-drying techniques compared with granulation (drug-to-resin ratios of 1:4 and 1:6). Characterization studies such as differential scanning calorimetry, X-ray diffraction, spectroscopic techniques, and drug release studies differentiated complexes from the physical mixtures. Binding studies between them revealed that the binding was linear with solubility of the drug limiting the adsorption capacity.
Results of the study highlighted the importance of the preparation methodologies to formulate complexes. When the drug and the resin were simply mixed physically, no complexation occurred. Thus, a careful evaluation of manufacturing procedure would indicate the nature and extent of complexation.
本工作旨在研究制备方法和药物与树脂的比例对利培酮与 Amberlite 树脂之间络合的影响。
该树脂络合物的存在可为制剂提供掩味特性。确定何时以及如何形成络合物非常重要。因此，在这项研究中，利培酮和 Amberlite 树脂的络合物通过颗粒化、溶液和冷冻干燥方法在不同的药物与树脂比例下制备。药物-树脂的物理混合物用于比较颗粒化、溶液和冷冻干燥制备的复合物的结果。通过各种特征化方法评估复合物，包括差示扫描量热法、X 射线衍射、光谱（近红外、傅里叶变换红外和拉曼）、药物释放和结合研究。
研究了各种制备方法中利培酮与 Amberlite 之间的络合作用。结果发现，当药物以溶液形式与树脂接触时，与颗粒化（药物与树脂的比例为 1:4 和 1:6）相比，络合作用在较低量的 Amberlite 树脂（药物与树脂的比例为 1:1 和 1:2）下发生，如溶液和冷冻干燥技术。如差示扫描量热法、X 射线衍射、光谱技术和药物释放研究等特征化研究将复合物与物理混合物区分开来。它们之间的结合研究表明，结合是线性的，药物的溶解度限制了吸附能力。
研究结果强调了制备方法在制剂中形成复合物的重要性。当药物和树脂简单地物理混合时，不会发生络合。因此，仔细评估制造程序将表明络合的性质和程度。
