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目的考察环糊精(CD)及CD/水溶性高分子体系对全反式维A酸(ATRA)的增溶作用。方法通过绘制相溶解度图,考察不同CD与ATRA的包合情况,并以常用凝胶基质为水溶性高分子聚合物,考察其对ATRA/CD包合物相溶解度图的影响。结果α-CD、β-CD、γ-CD与ATRA形成1:1包合物,2-羟丙基-β-环糊精(HP-β-CD)在其浓度低于6%时,形成1:1包合物,高于此浓度则形成1:2包合物,在上述各CD最高浓度溶液中,ATRA溶解度分别为纯水溶液的5.5、15.1、24.2和34.6倍;加入水溶性高分子聚合物能进一步提高ATRA/β-CD包合物稳定常数和ATRA溶解度,且CMC-Na作用最为显著,0.5%CMC-Na的加入可使ATRA/β-CD包合物稳定常数增加4.6倍,而ATRA的最大溶解度进一步增加(为水和1.8%β-CD溶液的247.4和16.4倍)。结论以CMC-Na为基质、β-CD为增溶剂制备ATRA外用制剂,可能增加单位制剂ATRA浓度,降低潜在不良反应。
Objective To investigate the solubilization of all-trans retinoic acid (ATRA) by cyclodextrin (CD) and CD / water-soluble macromolecular system. Methods The solubility of ATRA / CD inclusion complexes was investigated by plotting the phase solubility of different CDs. The effects of various CD and ATRA inclusion complexes on the solubility of ATRA / CD inclusion complexes were investigated by using the commonly used gel matrix as a water-soluble polymer. Results α-CD, β-CD and γ-CD form a 1: 1 inclusion complex with ATRA and HP-β-CD formed at concentrations below 6% 1: 1 inclusion complex. Above this concentration, a 1: 2 inclusion complex was formed, and the ATRA solubility of each of the above CDs was 5.5, 15.1, 24.2 and 34.6 times that of the pure water solution respectively. The addition of 0.5% CMC-Na can increase the stability constant of ATRA / β-CD inclusion complex by 4.6 times, and the stability of ATRA / β-CD inclusion complex and ATRA solubility can be further improved. While the maximum solubility of ATRA is further increased (247.4 and 16.4 times for water and 1.8% β-CD solution). Conclusion The preparation of ATRA external preparation with CMC-Na as substrate and β-CD as solubilizer may increase the concentration of ATRA in unit preparation and reduce the potential adverse reactions.