Richter Telse, Keipert Sigrid
Mathematisch-Naturwissenschaftliche Fakultät I, Humboldt University, Berlin, Germany.
Eur J Pharm Biopharm. 2004 Jul;58(1):137-43. doi: 10.1016/j.ejpb.2004.03.010.
The components of a carrier formulation can interact with an added drug as well as with the membrane surface they were applied on. Therefore, they can influence permeability of the membrane and permeation of the drug. The particular membrane structure might lead to different drug permeation out of one and the same carrier formulation. In this study, in vitro permeability of androstenedione (AD) as a highly lipophilic substance was investigated in excised bovine nasal mucosa, porcine cornea and the artificial cellulose membrane Nephrophan. Two microemulsions (ME) with either the addition of the co-surfactants hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD; ME-CD) or propylene glycol (PG, ME-PG) were tested in order to be used as carrier systems. Both MEs also consisted of 5% isopropyl myristate (IPM), 20% Cremophor EL (CrEL), and water. Buffer solution (EBS) with 0.0025% AD served as control solution and was furthermore compared to 0.0025% AD/buffer-solutions containing the ME components HP-gamma-CD in different concentrations (0.012, 0.024, 9%) as well as 20% CrEL. The AD-permeation behaviour through the three tissues was differently influenced by the MEs. The apparent permeability coefficients (Papp) of nasal mucosa for both ME systems did not differ from the Papp of the AD/buffer solution. In case of the other two barriers (cornea, Nephrophan, ME-PG as well as ME-CD provoked extended time lags for AD to permeate, so the Papp could not be calculated or declined to zero. Papp of AD/buffer solution without any additives resulted for cornea, nasal mucosa and Nephrophan in a ratio of 1:3:4. CrEL and 9% HP-gamma-CD diminished the Papp, except HP-gamma-CD in molar AD/HP-gamma-CD-ratios of 1:1 (0.012%) and 1:2 (0.024%). It seems that the composition of lipophilic and hydrophilic structures of the carrier systems or the additives had a higher impact on the Papp of cornea than on the Papp of the other tissues. Structure and character of the different membranes are considered to be mainly responsible for the differentiated permeation behaviour.
载体制剂的成分可与添加的药物相互作用，也可与它们所应用的膜表面相互作用。因此，它们会影响膜的通透性和药物的渗透。特定的膜结构可能导致同一载体制剂中药物的不同渗透情况。在本研究中，在切除的牛鼻黏膜、猪角膜和人工纤维素膜Nephrophan中研究了作为高亲脂性物质的雄烯二酮（AD）的体外通透性。测试了两种分别添加了助表面活性剂羟丙基-γ-环糊精（HP-γ-CD；ME-CD）或丙二醇（PG；ME-PG）作为载体系统的微乳剂（ME）。两种ME均还含有5%肉豆蔻酸异丙酯（IPM）、20%聚氧乙烯蓖麻油（CrEL）和水。含有0.0025%AD 的缓冲溶液（EBS）用作对照溶液，并进一步与含有不同浓度（0.012%、0.024%、9%）的ME成分HP-γ-CD以及20% CrEL的0.0025% AD/缓冲溶液进行比较。ME对AD通过三种组织时渗透行为的影响各不相同。两种ME系统作用下鼻黏膜对AD的表观渗透系数（Papp）与AD/缓冲溶液的Papp没有差异。对于另外两种屏障（角膜、Nephrophan），ME-PG以及ME-CD导致AD渗透的时间滞后延长，因此无法计算Papp或其降至零。不含任何添加剂的AD/缓冲溶液的Papp在角膜、鼻黏膜和Nephrophan中的比例为1:3:4。CrEL和9% HP-γ-CD降低了Papp，但AD与HP-γ-CD摩尔比为1:1（0.012%）和1:2（0.024%）时的HP-γ-CD除外。似乎载体系统或添加剂的亲脂性和亲水性结构组成对角膜Papp的影响比对其他组织Papp的影响更大。不同膜的结构和特性被认为是造成不同渗透行为的主要原因。
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