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Êîäèðîâêà:

Ïîèñêîâûå ñëîâà: m 80


â °



112

. . -. . 2. . 2013. . 54. 2

541.182.64:543.42.062:543.45

80
.. , .. ( , zadymova@colloid.chem.msu.ru)
- (Am ­ ) (GML ­ ), (-) 80 (Tw). (Tw+GML, Tw+Am, Tw+GML+Am): , , , . - (Tw+GML+Am) 4,2 , (Tw+Am). Am Tw , Am, .

: , , - , , , 80.

- () . () () , , , , . [1­7], (+), . () . () [8], ( + + ) . ( , , , , ) , -

, . 80 (Tw), (20) (Mw), 1308 , - (), 15 [9]. («.»), «Serva», . () , , 4,6â10­5 (20°C, 0,01 .% ). ­ (Am) (GML). ((RS)-3- 5- 2-(2- )-4-(2-)-6-1,4 -3,5-) «Afine Chemicals Limited» (Mw = 408,9 , 99% ) , ­4 (1,8â10 M [10]), . , , , . Am


. . -. . 2. . 2013. . 54. 2

113

500 , [11]. GML (2,3­ ) «Dermofeel» (Mw = 274,4 , = 5,2 [12], «.») , , (3,6â10­4 M 37° [13]), [14, 15]. , , (0,01 .%) («Merck»). , (PEG 400, Mw = 400 , () 8,65) «Sigma-Aldrich» («..») . (S) 80 (Tw = 3­12 ) - («Agilent 8453», ). 80 ( ) . (0,22 , «Millipore») (60/40 ), , ( = 6450 ­1­1, = 364 ). 6,5 , ­ 50 . , , . , [16], GML 80. [17]. (nD) ±5â10­5 «-23» (). ( = 0,997 /3 20°) (nD = 1,467) GML [18]. 80

, . , 80 ( ), - ( GML, Am). (D0) (Rh ­ ) (DLS), (N) ­ (SLS) «PhotoCor SP» ( = 632,8 ). («Millipore», 0,22 ). [19, 20]. , ( ), . , ­ , ­ . ( ). «MF-Millipore» ( 0,22 , 150 , 75%). [21]. (IAm), t, : I
Am

= CAmV/0,
3

(1)

V ­ (7,5 ); 0 ­ , , (0,71 2); CAm ­ t, (364 = 6950 ­1­1). ( ) . Am GML 80 . 1. 80, -


114

. . -. . 2. . 2013. . 54. 2

. 1. (1) (2) 80, (3) 80, GML, 295

A2 ­ ; C ­ ( ) ( ); R90 = (R90, ­ R90,KKM) ­ . (R90) . 2. , FD (. 2) A2, Mm = 1/FD. FD Mm . 1. Mm = NTw
Tw

+ NSolSol,

(3)

GML. , , Tw = 12 SAm (Sw = 2,3â10­4 M) 22 , GML 80 ­ 31 . w GML 14,6 [13]. . 1, S(Tw) , () [22, 23]. (NSol) (NTw) . (. 1) . 1. (Tw + Sol), ­ (Tw + Sol1 + Sol2). (Mm) SLS [24]: K /(2R90 ) = FD = 1/Mm + 2A2, (2) K ­ [24], ; = ( ­ KKM) ­ (/3); FD ­ ;

[19]: N
Tw

= Mm/(Tw + Sol) (4)

NSol = CENTw,

NTw NSol ­ 80 ; Tw Sol ­ 80 . (. 1) (4) NTw NSol (. 1). 80, (Sol1 Sol2), Mm = NTw
Tw

+ NSol1

Sol1

+ NSol2

Sol2,

. 2. () 80 (1), (2 ­ Am, 3 ­ GML) (4 ­ GML+Am); = Tw (1); = Tw+SSol (2, 3); = Tw+ SGML + SAm (4)


. . -. . 2. . 2013. . 54. 2 1 80 295 ( ­ ; m ­ ; NTw, NGML, NAm ­ ; nw/OE ­ ; V0, R0, S0 ­ , , ; ­ ; Rh ­ ; hPOE ­ ) GML () CE *dn
632,8

115

Am () NAm/NTw = 0,39 0,1403
7

GML + Am NAm/NTw = 0,56 0,1391 1,40â10­ 0,0077 9,11â10­ 66±0,3 30±1 38±0,4 13±0,5 42,6 2,2 60,8 0,28 5,6 3,4
7

0 0,1299 1,22â10­ 0,0027 2,26â10­ 34±0,3 0 0 6±0,5 17 1,6 32,2 - 3,6 2,0
7

N /dC, /
3

GML

/NTw = 0,45

0,1315 1,25â10­ 0,0058 1,08â10­ 65±0,3 29±1 0 9±0,5
5

*Ko, 2/2 *dR90/dC, 2/ *FD, m , NTw NGML NAm n
w/OE 3 ­1

1,43â10­ 0,0024 2,97â10­ 23±0,3 0 9±0,2 14±0,5 11,5 1,4 24,6 0,16 3,9 2,5

7

5

6

5

92600±400

33640±120

109830±400

44160±320

Vo, R, S, Rh, h
POE

41,8 2,15 58,1 - 5,0 2,85
1 2

2

,

*, m . 2. (C, /3) (Tw + SSol) (Tw+SSol + SSol ) - .

[20]: NSol1 = 1NTw; N N
Tw Sol2

= 2NTw,
Sol1

(5) (6)

= Mm /(Tw + 1

+ 2 Sol2),

Sol1, Sol2 ­ ; 1 = NGML/NTw 2 = NAm/NTw . 1 . (. 1) , GML ( 2 ) . , 80

. . Tw GML, . , GML 4,2 (. 1). . [25], , - (nw/OE). (Vh = 4Rh3/3), DLS, , (Vth), SLS, , ..


116

. . -. . 2. . 2013. . 54. 2

[26], . 80 GML : n
w/OE

= (Vh ­ Vth)0NA/(20NTwM0),

(7)

M0 0 ­ , 20 ­ - 80, NA ­ . GML (­COOCH2CHOHCH2OH), 4 -, , , : n
w/OE

= (Vh ­ Vth) 0NA/[(20NTw + 4NGML) M0]. (8)

, , : Vth = i NiMwi/(NAi), (9) Ni, Mwi i ­ , i- ; Tw, GML Am 1,082, 0,997 1,227 /3 ( 20°). . 1. 80 (. 1) nw/OE [26] (nw/OE 6 1 -). , , . . 1 , GML Am . , , -, . Am , () . , , PEG 400, , , (nw/OE = 14±1, . 1). , 15 .% PEG 400. [27, 28], - , , . Am ( 5 Tw GML)

( = 1,9-80), , . (), , [29­31] . 2. , (.. ) . ( = 79,5-70,2) , 366 (. 2). ( = 54,3-40,9) Am 364 , ( = 1,9), , ­ 357 . = 364 , , 15%- PEG 400 (366 ), Am . , POE- ( , ). Am (Am = 0-2,2510­4 M) , 72,7 49,6 /2. Am 3,710­6 /2, («» , S) ­ 0,45 2. (Ni) : (V0), (R0), (S0) ( = NAmS/S0), POE- (hPOE = Rh ­ R0). (Vi) , , V0 : V0 = i NiVi, (10) 0,32 3 0,5 GML Tw [22]. , Am, , 0,45 2. . 1. ,


. . -. . 2. . 2013. . 54. 2 2 ( 4,6% PEG 400 10% PEG 400 12,5% PEG 400 *15% PEG 400 21,4% PEG 400 30% EtOH 40% EtOH Tw Tw GML 50% EtOH 55% EtOH 65 % EtOH 75 % EtOH EtOH PEG 400 **


117

), , () 25°C [29-31] 79,5 78,1 75,6 74,5 73,3 70,2 60,1 54,3 ­ ­ 48,7 46,0 40,9 35,9 24,5 14,1 1,9 366 366 366 366 366 366 365 364 364 364 364 364 364 363 362 361 357 < 20 55 > > 20 > 55

. , * ** , - Tw+Am Tw+GML+Am. [29], PEG 400 [30], [31].

R0 80, 2,3 [22]. , , [22]. Am GML . Tw+GML+Am V0, R0, S0 hPOE. NAm Tw+Am Tw+GML+Am, , 30 GML ( 29 ). : -, GML, , - 80.

(«») (im), [32, 33]: i = i /i ,
m a m m a

(11)

i i ­ , a [33]. i [33]. i Siw/w Siw/55,43,
a

(12)

Siw w ­ ( 295 w = 55,43 ). a i . 3.


118

. . -. . 2. . 2013. . 54. 2

: i = NSoli /iNi,
m

(13)

NSoli ­ ; iNi ­ (. 1). im (11) (12) (13). 0 G [32]:
0 G = ­ RT ln i , m

(14)

R ­ , T ­ (). im G0 . 3. GML, , 2-, 0 (G CH2). - (. 3) G0CH2 = ­2,48 /, [32] ( ) , . G0CH2 [27]. ,
m

[22, 34] . G0 80 , GML, (. 3). , , , , . , (N­HO) [35], , , - . Am, -, H0> TS0. 80 - , GML. 12 80 . 3. , , , 100 . , , . . 3 [36] ,
3

(i ), m (i ), (G°), (G°CH ) 2 80 295 (Tw+Sol) GML im, ..
i m

(Tw+Sol1+Sol2) 1 (Sol1) 2 (Sol2) 0,28
4

0,28
4

GML 0,22

0,31 4,75â10 ­26,4 ­2,4
m

6,78â10 ­27,3 ­

4

3,45â10 ­25,6 ­2,3

6,78â104 ­27,3 ­

G°, / G°CH , /
2

i (Siw, M) a a a (i ): Am - Siw = 2,30â10­4 M i = 4,15â10­6 . .; GML - Siw = 3,60â10­4 M [13] i = 6,49â10­6 . .


. . -. . 2. . 2013. . 54. 2

119

. 3. Tw+Am (1) Tw+GML+Am (2), Tw+GML+Am (3) 12 . - , ­

, :
1/2 1/2 IAm = 2Am(D0/) t ,

(15)

Am ­ 80 , (. 1); D0 ­ , DLS. (. 3), . , , . . 3 , GML 80 25%. , Tw+GML+Am

4,2 , Tw+Am ( . 1). , Ñ , , , Tw ( . 1). , Tw = 12 ­ GML 3,15â1017, ­ 1,09â1017 /3. (15) . 80 GML (. 1) . . 3 ( 3) Tw = 12 , (Tw+GML+Am). , 80 1­2 . 80 . , , .

( 11-08-00492-).
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120 17. .., .. // . ., 2006. . 141. 18. http://www.chemspider.com/Chemical-Structure.66900 19. .., .., .., .. // .. 2004. 66. 2. . 175. 20. .. // . « ». -, , , ., 2009. . XVI. . 2. . 90. 21. Kantarci G., Ozguney I., Karasulu Y., Arzik S., Guneri T. // AAPS PhamSciTech. 2007. 8. Iss. 4. P. 75. 22. .. - . ., 1992. 23. Edwards D.A., Luthy R.G., Liu Z. // Environ. Sci. Technol. 1991. 25. P. 127. 24. .. . .. 1986. 25. Shick M.J. Nonionic surfactants. N.Y., 1967. P. 569. 26. Schott H. // J. Colloid Sci. 1967. 24. P. 193 27 . ., . ., . . C. , . ., 1980. . 142.

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10.12.12

SIMULTANEOUS SOLUBILIZATION OF LIPOPHILIC DRUG, AMLODIPINE, AND GLYCERYL MONOLAURATE IN AQUEOUS MICELLAR SOLUTIONS OF TWEEN 80
N.M. Zadymova, N.I. Ivanova (Division of Colloid Chemistry)
Solubilization and co-solubilization of lipophilic amlodipine (Am ­ antihypertensive drug) and glyceryl monolaurate (GML ­ enhancer of the skin permeability) in micelles of Tween 80 (Tw) in water medium were studied using UV-spectroscopy and refractometry. Such properties of the mixed micelles (Tw + GML, Tw + Am, Tw + GML + Am) as aggregation numbers of components, locus of solubilizates, diffusion coefficients, sizes, and hydration were investigated. The ternary micelle (Tw + GML + Am) includes in 4,2-times more molecules of drug than the two-component one. It was shown that the diffusion of mixed micelles (Tw + Am, Tw + GML + Am) defines the mass transfer of Am in aqueous solutions.

Key words: micelles of surfactant, solubilization, co-solubilization of drug and enhancer of the skin permeability, amlodipine, glyceryl monolaurate, Tween 80.
: - . . . , . . , (zadymova@colloid.chem.msu.ru); - , . . (ini@colloid.chem.msu.ru).