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DOUBLE-SINK (Soy Lecithin 20% wt/vol in Dodecane, SINK in Acceptor)
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Figure 743 Gradient pH pro les for two nonionizable molecules: double-sink conditions, 20% wt/vol soy lecithin in dodecane
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Table 718 lists the interpolated apparent and membrane permeabilities, along with the membrane retentions, of the probe molecules used in the gradient pH study, at pH values 50, 55, 60, 65, and 74 77610 Collander Relationship between 2% DOPC and 20% Soy Intrinsic Permeabilities The 20% soy lecithin (Table 717) and the 2% DOPC (Table 715) intrinsic permeabilities may be compared in a Collander equation, as shown in Fig 744 The slope of the regression line, soy versus DOPC, is greater than unity This indicates that the soy membrane is more lipophilic than the DOPC membrane Intrinsic permeabilities are generally higher in the soy system Three molecules were signi cant outliers in the regression: metoprolol, quinine, and piroxicam Metoprolol and quinine are less permeable in the DOPC system than expected, based on their apparent relative lipophilicities and in vivo absorptions [593] In contrast, piroxicam is more permeable in DOPC than expected based on its relative lipophilicity With these outliers removed from the regression calculation, the statistics were impressive at r 2 0:97 777 Evidence of Transport of Charged Species
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In Section 48 the topic of charged-species absorption ( fact or ction ) was rst considered The partitioning properties of some lipophilic charged molecules in the
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log P0 (SD) MW 3028 4546 2593 2674 3244 2303 2543 3314 3308 2363 3509 1882 2743 2977 1016 907 953 956 409, 855 432 412 233, 522 367, 1093 831 867, 1012 981, 1025 37 39 45 60 51 62 62 67 46 82 pH Rangec 30 100 30 90 30 100 48 100 36 100 30 84 30 84 30 90 30 66 30 100 60 100 30 100 30 100 30 100 421 (41) 412 (35) 418 (47) 412 (35) 156 (06) 518 (16) 228 (10) 263 (08) 170 (10) 44f 198 (102) 17f 17f 17f 438 (004) 439 (004) 438 (005) 439 (004) 481 (002) 429 (001) 464 (002) 458 (001) 477(003) 436 470 (022) 477 477 477 Pu 10 6 cm=s (SD)b log Pu (SD) pKa FLUX I 0:01 M; 25 C pKa nd 12 11 12 9 11 8 8 11 7 12 7 12 12 5 GOFe 24 20 26 17 07 07 07 05 04 10 04 05 10 08
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TABLE 717 Intrinsic Permeabilities and the Unstirred Water Layer Permeabilities Determined from Gradient pH Dependence of Effective Permeabilities: 20% Soy Lecithin in Dodecane, Sink in Acceptor
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P0 (cm/s) (SD)a
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Desipramine Verapamil Propranolol Metoprolol Quinine Naproxen Ketoprofen Piroxicam Furosemide Carbamazepine Ranitidine Antipyrine Terbutaline Hydrochlorothiazide
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19 (08) 10 2 11 (03) 10 1 6 (2) 13 (03) 10 1 50(07) 10 2 51 (04) 10 3 33 (03) 10 3 79 (06) 10 4 13 (01) 10 4 94 (06) 10 5 56 (06) 10 6 14 (02) 10 6 12 (02) 10 7 5 (6) 10 9
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227 (019) 103 (014) 079 (015) 088 (010) 130 (006) 230 (004) 249 (005) 311 (003) 390 (003) 403 (003) 525 (004) 586 (006) 691 (008) 830 (049)
P0 intrinsic permeability, SD estimated standard deviation Pu unstirred water permeability c Data range actually used in the regression analysis d Number of Pe measurements e GOF goodness of t in the weighted nonlinear regression analysis f Carbamazepine, antipyrine, terbutaline, and hydrochlorothiazide were treated as neutral molecules Their effective permeabilities were corrected for the unstirred water layer using estimated unstirred water layer permeabilities, determined by the other molecules of similar lipophilicities and size
TABLE 718 Interpolated Apparent and Membrane Permeabilities Determined from Double-Sink Conditions: 20% Soy Lecithin in Dodecane