New, highly efficient formulation of diclofenac for the topical, transdermal administration in ultradeformable drug carriers, Transfersomes
New, highly efficient formulation of diclofenac for the topical, transdermal administration in ultradeformable drug carriers, Transfersomes
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DOI：
10.1016/s0005-2736(01)00369-8
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发表时间：
2001-10-01
影响因子：
3.4
通讯作者：
Blume, G
中科院分区：
文献类型：
--
作者：
Cevc, G;Blume, G
Transfenac是双氯芬酸的一种乳液状制剂。它由药学上可接受的成分组成，并介导药物通过完整皮肤转运并进入目标组织。即使在Transfenac给药剂量低于0.5 mg/kg体重时，靶组织中也能达到具有治疗意义的药物浓度。超可形成的药物载体，称为转移体，构成Transfenac的基础，这些转移体被认为在经皮水活性梯度的影响下自发地穿过皮肤(见Biochim。Biophys。学报1104(1992)226]。双氯芬酸与超可变形载体的结合使其具有更长的效果，并且与商业水凝胶中的药物相比，其在皮肤下组织中的浓度达到高10倍。例如，当给药剂量范围为0.25- 2mg /kg大鼠体重时，根据组织深度，Transfenac在t = 12 h时达到0.5 - 2mg /g和2 - 20mg /g的肌内药物浓度。水凝胶中较高的药物浓度（1.25-10毫克/公斤体重）使肌肉中的药物水平仅< 0.5马克杯/克。这两种剂型在大鼠髌骨中的药物浓度分别在1 ~ 5杯/g或0.4杯/g之间。在小鼠、大鼠和猪中观察到，通过超变形载体递送双氯芬酸的相对优势随着处理过的肌肉厚度和药物剂量的减少而增加；这可以通过假设与载体相关的药物通过真皮毛细血管丛的清除效率较低来解释。在猪中，每公斤体重使用0.3毫克双氯芬酸在高度可变形的囊泡中，分布在25厘米(2)的面积上，以确保治疗药物浓度在5厘米内。厚肌标本，采集于药剂施用部位下。当药物在水凝胶中以8倍高的剂量使用时，平均肌内浓度至少降低3倍，并且无治疗作用。这表明，双氯芬酸在Transfersomes中有可能取代口服/外用双氯芬酸联合给药。(C) 2001年Elsevier Science B.V.出版
Transfenac, a lotion-like formulation of diclofenac, is described. It consists of pharmaceutically acceptable ingredients and mediates the agent transport through intact skin and into the target tissues. Therapeutically meaningful drug concentrations in the target tissue are reached even when the administered drug dose in Transfenac is below 0.5 mg/kg body weight. Ultradeformable agent carriers, called Transfersomes, form the basis of Transfenac, These Transfersomes are proposed to cross the skin spontaneously under the influence of transepidermal water activity gradient (see [Biochim. Biophys. Acta 1104 (1992) 226]). Diclofenac association with ultradeformable carriers permits it to have a longer effect and to reach 10-times higher concentrations in the tissues under the skin in comparison with the drug from a commercial hydrogel. For example, Transfenac achieves intramuscular agent concentrations between 0.5 and 2 mug/g and 2 and 20 mug/g at t = 12 h, depending on the tissue depth, when it is administered in the dose range 0.25-2 mg/kg of rat body weight. A much higher drug concentration in a hydrogel (1.25-10 mg/kg body weight) creates the drug level of only < 0.5 mug/g in the muscle. The drug concentration in the rat patella for these two types of formulation is between 1 mug/g and 5 mug/g or 0.4 mug/g, respectively. The relative advantage of diclofenac delivery by means of ultradeformable carriers increases with the treated muscle thickness and with decreasing drug dose, as seen in mice, rats and pigs; this can be explained by assuming that the drug associated with carriers is cleared less efficiently by the dermal capillary plexus. In pigs it suffices to use 0.3 mg of diclofenac in highly deformable vesicles per kg body weight, spread over an area of 25 cm(2), to ensure therapeutic drug concentration in a 5-cm. thick muscle specimen, collected under the agent application site. When the drug is used in a hydrogel at 8 times higher dose, the average intramuscular concentration is at least three times lower and subtherapeutic. This suggests that diclofenac in Transfersomes has the potential to replace combined oral/topical diclofenac administration in humans. (C) 2001 Published by Elsevier Science B.V.