Development and evaluation of a tacrolimus cream formulation using a binary solvent system.
Development and evaluation of a tacrolimus cream formulation using a binary solvent system.
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DOI：
10.1016/j.ijpharm.2014.01.017
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发表时间：
2014-04
影响因子：
5.8
通讯作者：
M. Yamanaka;S. Yokota;Y. Iwao;Shuji Noguchi;S. Itai
中科院分区：
文献类型：
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作者：
M. Yamanaka;S. Yokota;Y. Iwao;Shuji Noguchi;S. Itai
我们开发了一种油/水型他克莫司 (FK506) 乳膏配方，作为普特彼软膏的替代品，用于治疗特应性皮炎。我们确定了外用制剂中使用的溶剂对 FK506 溶解度和稳定性的影响，并评估了 FK506 从溶液、乳液和乳膏中经皮吸收到大鼠皮肤中的情况。筛选表明癸二酸二乙酯 (DES)、肉豆蔻酸异丙酯 (IPM)、丙二醇 (PG) 和油醇 (OA) 是合适的 FK506 溶剂。当使用这些溶剂制备的 FK506 溶液经皮给药时，DES 和 IPM 的 AUC0-24 值高于或类似于 0.1% Protopic 软膏。 PG 和 OA 的 AUC0-24 值较低，因此这些溶剂不会增强吸收。 70℃孵育9 d后，DES和IPM溶液中FK506的残留率分别为95.6%和88.6%，因此选择DES和IPM制备乳液。当乳剂透皮给药时，IPM乳剂AUC0-24值增加4.6倍； DES乳液没有表现出高透皮吸收，但表现出持续的特性。由IPM和DES的混合物制备的乳膏制剂也表现出高吸收性，并且随着IPM比例的增加，透皮吸收也增加。我们通过控制 IPM:DES 比例开发了一种 FK506 乳膏配方，该配方具有可控的透皮吸收率。
We developed an oil/water-type tacrolimus (FK506) cream formulation as an alternative to Protopic ointment for atopic dermatitis treatment. We determined the effects of solvents used in topical preparations on FK506 solubility and stability, and evaluated FK506 transdermal absorption into rat skin from solutions, emulsions, and creams. Screening indicated that diethyl sebacate (DES), isopropyl myristate (IPM), propylene glycol (PG), and oleyl alcohol (OA) were adequate FK506 solvents. When FK506 solutions prepared using these solvents were transdermally administered, AUC0–24values for DES and IPM were higher than or similar to that for 0.1% Protopic ointment. The AUC0–24values for PG and OA were low, so these solvents did not enhance absorption. The residual ratios of FK506 in DES and IPM solutions after incubation at 70 °C for 9 d were 95.6% and 88.6%, respectively, so DES and IPM were chosen for emulsion preparation. When the emulsions were transdermally administered, the IPM emulsion AUC0–24values increased 4.6-fold; DES emulsions did not show high transdermal absorption, but showed sustained characteristics. A cream formulation prepared by mixture of IPM and DES also showed high absorption and transdermal absorption increased with increasing IPM ratio. We developed an FK506 cream formulation with a controllable transdermal absorption rate by manipulating the IPM:DES ratio.