The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510700, China; The State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong, China; The Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
Jiangsu Provincial Xuzhou Pharmaceutical Vocational College, Xuzhou 221116, China.
Mater Sci Eng C Mater Biol Appl. 2020 Jun;111:110836. doi: 10.1016/j.msec.2020.110836. Epub 2020 Mar 17.
Solid dispersion is a widely used method to improve the dissolution and oral bioavailability of water-insoluble drugs. However, due to the strong hydrophobicity, the drug crystallization in the release media after drug dissolution and the resulted decreased drug absorption retards the use of solid dispersions. It is widely known that the amphiphilic copolymer can encapsulate the hydrophobic compounds and help form stable nano-dispersions in water. Inspired by this, we tried to formulate the solid dispersion of nimodipine by using amphipathic copolymer as one of the carriers. Concerning the solid dispersions, there are many important points involved in these formulations, such as the miscibility between the drug and the carriers, the storage stability of solid dispersions, the dissolution enhancement and so on. In this study, a systemic method is proposed. In details, the supersaturation test and the glass transition temperature (T) measurement to predict the crystallization inhibition, the ratios of different components and the storage stability, the interactions among the components were investigated in detail by nuclear magnetic resonance (H NMR) and isothermal titration calorimetry (ITC) and, the final dissolution and oral bioavailability enhancement. It was found that the amphiphilic copolymer used in the solid dispersion encouraged the formation the drug loading micelles in the release media and, finally, the problem of drug crystallization in the dissolution process was successfully solved.
固体分散体是一种广泛用于提高水不溶性药物溶解和口服生物利用度的方法。然而，由于其强疏水性，药物在药物溶解后的释放介质中结晶，导致药物吸收减少，限制了固体分散体的应用。众所周知，两亲共聚物可以包裹疏水性化合物，并有助于在水中形成稳定的纳米分散体。受此启发，我们尝试使用两亲共聚物作为载体之一来制备尼莫地平的固体分散体。关于固体分散体，这些配方涉及许多重要的方面，例如药物与载体之间的混溶性、固体分散体的储存稳定性、溶解增强等。在本研究中，提出了一种系统的方法。详细地说，通过超饱和度测试和玻璃化转变温度（T）测量来预测结晶抑制、不同成分的比例和储存稳定性、成分之间的相互作用等方面进行了详细研究，最终提高了药物的溶解和口服生物利用度。结果发现，固体分散体中使用的两亲共聚物促进了药物在释放介质中载药胶束的形成，最终成功解决了药物在溶解过程中结晶的问题。
