In vitro permeation studies comparing bovine nasal mucosa, porcine cornea and artificial membrane: androstenedione in microemulsions and their components.
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.
Richter
Telse
T
Mathematisch-Naturwissenschaftliche Fakultät I, Humboldt University, Berlin, Germany.
Keipert
Sigrid
S
D000735:Androstenedione / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D002417:Cattle; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D004655:Emulsions; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D013552:Swine
D004655:Emulsions; D008567:Membranes, Artificial; D000735:Androstenedione