Tran Phuong, Pyo Yong-Chul, Kim Dong-Hyun, Lee Sang-Eun, Kim Jin-Ki, Park Jeong-Sook
College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea.
College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Korea.
Pharmaceutics. 2019 Mar 19;11(3):132. doi: 10.3390/pharmaceutics11030132.
Approximately 40% of new chemical entities (NCEs), including anticancer drugs, have been reported as poorly water-soluble compounds. Anticancer drugs are classified into biologic drugs (monoclonal antibodies) and small molecule drugs (nonbiologic anticancer drugs) based on effectiveness and safety profile. Biologic drugs are administered by intravenous (IV) injection due to their large molecular weight, while small molecule drugs are preferentially administered by gastrointestinal route. Even though IV injection is the fastest route of administration and ensures complete bioavailability, this route of administration causes patient inconvenience to visit a hospital for anticancer treatments. In addition, IV administration can cause several side effects such as severe hypersensitivity, myelosuppression, neutropenia, and neurotoxicity. Oral administration is the preferred route for drug delivery due to several advantages such as low cost, pain avoidance, and safety. The main problem of NCEs is a limited aqueous solubility, resulting in poor absorption and low bioavailability. Therefore, improving oral bioavailability of poorly water-soluble drugs is a great challenge in the development of pharmaceutical dosage forms. Several methods such as solid dispersion, complexation, lipid-based systems, micronization, nanonization, and co-crystals were developed to improve the solubility of hydrophobic drugs. Recently, solid dispersion is one of the most widely used and successful techniques in formulation development. This review mainly discusses classification, methods for preparation of solid dispersions, and use of solid dispersion for improving solubility of poorly soluble anticancer drugs.
据报道，包括抗癌药物在内，约40%的新化学实体（NCEs）为水溶性差的化合物。基于有效性和安全性，抗癌药物可分为生物药物（单克隆抗体）和小分子药物（非生物抗癌药物）。生物药物由于分子量较大，通过静脉注射给药，而小分子药物优先通过胃肠道途径给药。尽管静脉注射是最快的给药途径，并能确保完全的生物利用度，但这种给药途径给患者带来了前往医院进行抗癌治疗的不便。此外，静脉给药可能会引起多种副作用，如严重的超敏反应、骨髓抑制、中性粒细胞减少和神经毒性。口服给药因其成本低、避免疼痛和安全等多种优点，是药物递送的首选途径。NCEs的主要问题是水溶性有限，导致吸收不良和生物利用度低。因此，提高难溶性药物的口服生物利用度是药物剂型开发中的一大挑战。人们开发了多种方法，如固体分散体、络合、脂质体系统、微粉化、纳米化和共晶体，以提高疏水性药物的溶解度。近年来，固体分散体是制剂开发中应用最广泛、最成功的技术之一。本综述主要讨论固体分散体的分类、制备方法以及固体分散体在提高难溶性抗癌药物溶解度方面的应用。
