Hegge A B, Schüller R B, Kristensen S, Tønnesen H H
School of Pharmacy, Department of Pharmaceutics, University of Oslo, Oslo, Norway.
Pharmazie. 2008 Aug;63(8):585-92.
Combinations of cyclodextrins and alginates were used to solubilize the hydrophobic compound curcumin in aqueous vehicles intended for topical delivery. A careful selection of the excipients is necessary to achieve a sufficient release of curcumin towards a membrane of hydrophilic character, e.g. mucosa. The aim of the study was to investigate the effect of different combinations of cyclodextrins and alginates on curcumin release towards hydrophilic membranes in vitro. The curcumin flux through semi-permeable membranes of different molecular weight cut-off was measured to differentiate between the flux of curcumin in its uncomplexed form (restricted flux), its uncomplexed form together with its inclusion complexes (partly restricted flux) and the overall flux of curcumin-cyclodextrin complexes and uncomplexed curcumin (unrestricted flux). A high viscosity of the vehicle was expected to inhibit curcumin flux. Vehicles containing 3% alginate were found to have lower unrestricted flux than the vehicles containing 0.5% alginate independent of the type of cyclodextrin used. The results indicate that the unrestricted curcumin flux (e.g. in the case of wounded skin) is rather independent of the composition of the hydrophilic vehicle and mostly limited by the viscosity. However, partly restricted and restricted curcumin flux were found to depend on both the viscosity and the composition of the vehicles. The cyclodextrin with the demonstrated lowest solubilisation capacity (i.e. hydroxypropyl-beta-cyclodextrin) resulted in the highest values of both the restricted and unrestricted curcumin flux. In conclusion, a combination of hydroxypropyl-beta-cyclodextrin and propylene glycol alginate seemed to be the best choice with respect to curcumin solubility and release from the vehicle.
环糊精与海藻酸盐的组合被用于在用于局部给药的水性载体中增溶疏水性化合物姜黄素。为了使姜黄素向亲水性膜（如粘膜）充分释放，必须仔细选择辅料。本研究的目的是研究环糊精和海藻酸盐的不同组合对姜黄素在体外向亲水性膜释放的影响。通过测量姜黄素透过不同截留分子量的半透膜的通量，以区分未复合形式的姜黄素通量（受限通量）、未复合形式及其包合物的通量（部分受限通量）以及姜黄素 - 环糊精复合物和未复合姜黄素的总通量（不受限通量）。预计载体的高粘度会抑制姜黄素通量。发现含有3%海藻酸盐的载体比含有0.5%海藻酸盐的载体具有更低的不受限通量，与所用环糊精的类型无关。结果表明，不受限的姜黄素通量（如在伤口皮肤的情况下）与亲水性载体的组成相当无关，并且主要受粘度限制。然而，发现部分受限和受限的姜黄素通量取决于载体的粘度和组成。具有最低增溶能力的环糊精（即羟丙基 - β - 环糊精）导致受限和不受限姜黄素通量的最高值。总之，就姜黄素的溶解性和从载体中的释放而言，羟丙基 - β - 环糊精和海藻酸丙二醇酯的组合似乎是最佳选择。
