Ibuprofen permeability

Ghosh [548] used cellulose nitrate microporous filters (500 pm thick) as scaffold material to deposit octanol into the pores and then under controlled pressure conditions, displace some of the oil in the pores with water, creating a membrane with parallel oil and water pathways. This was thought to serve as a possible model for some of the properties of the outermost layer of skin, the stratum comeum. The relative proportions of the two types of channel could be controlled, and the properties of 5-10% water pore content were studied. Ibuprofen (lipophilic) and antipyr-ine (hydrophilic) were model drugs used. When the filter was filled entirely with water, the measured permeability of antipyrine was 69 (in 10 6 cm/s) when 90% of the pores were filled with octanol, the permeability decreased to 33 95% octanol content further decreased permeability to 23, and fully octanol-filled filters indicated 0.9 as the permeability. 

Levis KA, Lane ME and Corrigan OI (2003) Effect of Buffer Media Composition on the Solubility and Effective Permeability Coefficient of Ibuprofen. Int J Pharm 253 pp 49-59. 

FIG. 12. Permeability of ibuprofen from different formulations via excised human stratum comeum. Redrawn from Stoye, L, Permeabilitdtsverdnderung von humanem Stratum corneum nach Applikation nicht-steroidaler Antirheumatika in verschiedenen kolloidalen Trdgersystemen, Ph.D. Thesis TU Braunschweig, 1997. 

Figure 6.17 The classification of 42 drugs in the (solubility-dose ratio, apparent permeability) plane of the QBCS. The intersection of the dashed lines drawn at the cutoff points form the region of the borderline drugs. Key 1 acetyl salicylic acid 2 atenolol 3 caffeine 4 carbamazepine 5 chlorpheniramine 6 chlorothiazide 7 cimetidine 8 clonidine 9 corticosterone 10 desipramine 11 dexamethasone 12 diazepam 13 digoxin 14 diltiazem 15 disopyramide 16 furosemide 17 gancidovir 18 glycine 19 grizeofulvin 20 hydrochlorothiazide 21 hydrocortisone 22 ibuprofen 23 indomethacine 24 ketoprofen 25 mannitol 26 metoprolol 27 naproxen 28 panadiplon 29 phenytoin 30 piroxicam 31 propanolol 32 quinidine 33 ranitidine 34 salicylic acid 35 saquinavir 36 scopolamine 37 sulfasalazine 38 sulpiride 39 testosterone 40 theophylline 41 verapamil HC1 42 zidovudine.

Fig. 12 Permeability of ibuprofen from different formulations via excised human stratum corneum. (Redrawn from RefP l)...

PAMPA-pKa fiux optimized design (pOD)-permeabiiity Iso-pH mapping unstirred PAMPA was used to measure the effective permeability, Pe, as a function of pH from 3 to 10, of five weak monoprotic acids (ibuprofen, naproxen, ketoprofen, salicylic acid, benzoic acid), an ampholyte (piroxicam), five monoprotic weak bases (imipramine, verapamil, propranolol, phenazopyridine, metoprolol), and a diprotic weak base (quinine). The intrinsic permeability, Po, the UWL permeability, Pu, and the apparent pKa (pKa.fiux) were determined from the pH dependence of log Pg. The underlying permeability-pH equations were derived for multiprotic weak acids, weak bases, and ampholytes. The average thickness of the UWL on each side of the membrane was estimated to be nearly 2000 p, somewhat larger than that found in Caco-2 permeability assays (unstirred). As the UWL thickness in the human intestine is believed to be about forty times smaller, it is critical to correct the in vitro permeability data for the effect of the UWL. Without such correction, the in vitro permeability coefficient of lipophilic molecules would be indicative only of the property of water. In single-pH PAMPA (e.g., pH 7.4), the uncertainty of the UWL contribution can be minimized if a specially selected pH (possibly different from 7.4) were used in the assay. From the analysis of the shapes of the log Pe-pH plots, a method to improve the selection of the assay pH, called pOD-PAMPA, was described and tested. From an optimally selected assay pH, it is possible to estimate Pg, as well as the entire membrane permeability-pH profile. 

Permeabihty coefficients for black rat snake were taken directly from Table II for ibuprofen, naproxen, ketoprofen, deoxycorticosterone, 1 la-hydroxyprogesterone, corticosterone, and hydrocortisone. Permeabihty coefficients for indomethacin and progesterone were not inclnded because they were not measured from aqueous solurion. Permeability coefficients for the parabens were not included because they are idenrical to those reported by Itoh, Xia, et al. (1990). 

Another interesting application important to the pharmaceutical industry is the measurement of the absorption profile of drugs through the skin. This application is normally accomplished through the use of a Franz diffusion cell (FDC) with quantification by HPLC. IMS methods are more rapid than and compared well with HPLC results when the transdermal analyses of ibuprofen were made. Using IMS, the skin permeability coefficient was found to be 0.013 cm/h, which matched those determined using HPLC. 

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