Lim Li Ming, Park Jin-Won, Hadinoto Kunn
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
Department of Chemical and Biomolecular Engineering, Seoul National University of Science and Technology, Seoul 01811, Korea.
Pharmaceutics. 2022 May 2;14(5):979. doi: 10.3390/pharmaceutics14050979.
Amorphization, typically in the form of amorphous solid dispersion (ASD), represents a well-established solubility enhancement strategy for poorly soluble drugs. Recently, two amorphous drug formulations, i.e., the amorphous drug-polyelectrolyte nanoparticle complex (nanoplex) and co-amorphous system, have emerged as promising alternatives to circumvent the issues faced by ASD (i.e., large dosage requirement, high hygroscopicity). In the present work, the nanoplex was benchmarked against the co-amorphous system in terms of the preparation efficiency, drug payload, thermal stability, dissolution rate, supersaturation generation, and accelerated storage stability. Weakly acidic curcumin (CUR) and weakly basic ciprofloxacin (CIP) were used as the model poorly soluble drugs. The CUR and CIP nanoplexes were prepared using chitosan and sodium dextran sulfate as the polyelectrolytes, respectively. The co-amorphous CUR and CIP were prepared using tannic acid and tryptophan as the co-formers, respectively. The benchmarking results showed that the amorphous drug nanoplex performed as well as, if not better than, the co-amorphous system depending on the drug in question and the aspects being compared. The present work successfully established the nanoplex as an equally viable amorphous drug formulation as the more widely studied co-amorphous system to potentially serve as an alternative to ASD.
非晶化，通常以无定形固体分散体（ASD）的形式存在，是一种成熟的提高难溶性药物溶解度的策略。最近，两种无定形药物制剂，即无定形药物 - 聚电解质纳米颗粒复合物（纳米复合物）和共无定形体系，已成为有前途的替代方案，以解决ASD面临的问题（即大剂量需求、高吸湿性）。在本研究中，从制备效率、药物载量、热稳定性、溶解速率、过饱和生成以及加速储存稳定性等方面对纳米复合物和共无定形体系进行了比较。弱酸性姜黄素（CUR）和弱碱性环丙沙星（CIP）被用作模型难溶性药物。分别使用壳聚糖和硫酸葡聚糖钠作为聚电解质制备CUR和CIP纳米复合物。分别使用单宁酸和色氨酸作为共形成剂制备共无定形CUR和CIP。比较结果表明，根据所讨论的药物和比较的方面，无定形药物纳米复合物的性能与共无定形体系相当，甚至可能更好。本研究成功地将纳米复合物确立为一种与研究更广泛的共无定形体系同样可行的无定形药物制剂，有可能作为ASD的替代品。
