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_g) 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 (¹H 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.

固体分散体是改善水不溶性药物的溶解度和口服生物利用度的广泛使用的方法。然而，由于强的疏水性，药物溶解后在释放介质中的药物结晶以及所导致的药物吸收减少阻碍了固体分散体的使用。众所周知，两亲共聚物可以包封疏水化合物并有助于在水中形成稳定的纳米分散体。受此启发，我们试图通过使用两亲共聚物作为载体之一来配制尼莫地平的固体分散体。关于固体分散体，这些制剂涉及许多重要方面，例如药物与载体之间的混溶性，固体分散体的储存稳定性，溶解度的提高等。在这个研究中，提出了一种系统的方法。详细地说，过饱和试验和玻璃化转变温度（T_g）预测结晶的抑制作用，不同组分的比例和储存稳定性，各组分之间的相互作用的测量已通过核磁共振（¹ H NMR）和等温滴定热分析（ITC）进行了详细研究，最终溶解和口服生物利用度提高。发现用于固体分散体的两亲共聚物促进了释放介质中载药胶束的形成，最终解决了药物在溶解过程中的结晶问题。