Percutaneous absorption of cyclizine and its alkyl analogues

(1)

(2)

(3)

(4)

(5)

(6)

(7)

(8)

(9)

(10)

(11)

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Chapter 4: Percutaneous delivery of cyclizine and its alkyl analogues

140

120

100

40

20 o

II

III

IV

Compound

FIGURE4-1: Melting points of (I) and its alkylanalogues.

68 - - - --

-0

₈₀

-

_c

.-

₀

c.

en

c

60 .-

-G)

:i

(84)

700

600

500 -E

-

C) :::1.

~400

-:s

_:s '0 U)

~ 300

o

CD :s

cr

«

200

100 o

591.4

II

III

IV

Compound

FIGURE 4-2: Aqueous solubilities of (I) and its alkyl analogues at 32 DC.

(85)

Log Kp

-4

FIGURE4-3: Permeability (log kp) and partition coefficients (log Koct)of (I) and its alkyl analogues.

70

--6

y

=

_R2O.514x+ 2.6151

₌

_0.9988 Log Koct

I

-5

-1:)

4 -

_..

c Q) 'u

is

3 Q) 0 u c 0

:e 2

_1:: as Q, CI .2 1 c as

-0

-

_I

-

I

i

II

I

III I

I IV

E -1 2i as Q)

E -2

Q) Q, CI 0 ...I

-3

(86)

Chapter4: Percutaneous delivery of cyclizine and its alkylanalogues

9

8

7

6.9522

6

3

2

1

_0.6864 0.1818

o

II

III

IV

Compound

FIGURE4-4:

Mean steady-state

flux

:t SD of (I) and its alkyl analogues from saturated aqueous solutions(n = 6).

(87)

FIGURE

4-5:

Permeation profiles of (I) and its alkyl analogues from the saturated aqueous solutions. 72 180 I

. Compound

J

.

CompoundOJ

.

. Comound 0

. CompoundIV

160 ;Y=0.138X+O.132

-

R2

=

0.9986 N 140 y- 6.9522x + 2.966 ... _R2_{= 0.9975} G :1 Y

=

0.2502 x+ 0.D88

-

₁₂₀

If

= 0.9982

CD ... /y

=

0.6864

x

+0.1335 ... -=

1UU

R2 = 0.9988 = CI E 80 CD

>

;

60 -

₌

E

=

u

40

20

0

5

10

15

20

25 SO

Time

(h)

(88)

(89)

(90)

(91)

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