A Parmaceutical Study on A Parmaceutical Study on Felodipine(Preparation and Felodipine(Preparation and evaluation of Felodipine evaluation of Felodipine Therapeutic Transdermal Therapeutic Transdermal systemsystem))

Ahmed Abd El-Bary , Mohamed M. NafadyAhmed Abd El-Bary , Mohamed M. Nafady ,, Mahmoud E. NasrMahmoud E. NasrDepartment of Pharmaceutics and Industrial Department of Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Cairo Pharmacy , Faculty of Pharmacy, Cairo University,EgyptUniversity,Egypt..

Aim of workAim of workTransdermal therapeutic Transdermal therapeutic systems were prepared in systems were prepared in order to control the order to control the permeation of the drug permeation of the drug through membranes and through membranes and develop a transdermal path develop a transdermal path to deliver felodipine at a to deliver felodipine at a controlled rate thus controlled rate thus bypassing the hepatic bypassing the hepatic metabolism of the drug and metabolism of the drug and increasing its increasing its bioavailabilitybioavailability..

The in-vivo evaluation of certain The in-vivo evaluation of certain selected formula of felodipine selected formula of felodipine therapeutic transdermal therapeutic transdermal system(microemulsion system(microemulsion composed of benzyl alcohol : composed of benzyl alcohol : water : transcutol : water : transcutol : taurodeoxycholate : tween20 taurodeoxycholate : tween20 in ratios of in ratios of 17.3:47.7:15.9:1.0:18.1 17.3:47.7:15.9:1.0:18.1 respectively ) in rabbits were respectively ) in rabbits were carried outcarried out..

ConclusionConclusion11--Permeation of felodipine through Permeation of felodipine through

EVA membranes increases EVA membranes increases significanly when the membranes significanly when the membranes are stored for three days in are stored for three days in contact with the drug solutioncontact with the drug solution..

22--The amount of felodipine The amount of felodipine permeated through membranes permeated through membranes with different levels of VA , with different levels of VA , copolymer increases as the copolymer increases as the weight fraction of the copolymer weight fraction of the copolymer increases , in the rank order increases , in the rank order 28%>19%>9% VA content28%>19%>9% VA content..

33--The permeation of felodipine from The permeation of felodipine from its microemulsion system IV its microemulsion system IV showed the highest amount of showed the highest amount of drug permeation compared to drug permeation compared to other microemulsion systemsother microemulsion systems..4-The effect of d-limonene as a 4-The effect of d-limonene as a

permeation enhancer on the permeation enhancer on the permeation of felodipine through permeation of felodipine through new born rabbit skin resulted in new born rabbit skin resulted in nearly about five fold increase in nearly about five fold increase in the amount of felodipine the amount of felodipine permeated through the skin.permeated through the skin.

5-Kinetic analysis of the 5-Kinetic analysis of the permeation data revealed that permeation data revealed that felodipine permeation through felodipine permeation through EVA membranes follows zero EVA membranes follows zero order diffusion and first order order diffusion and first order mechanisms.mechanisms.

6-From bioavailability study ; 6-From bioavailability study ; felodipine transdermal patches felodipine transdermal patches controlled the permeation of the controlled the permeation of the drug for an extended period of time drug for an extended period of time , resulting in a significant increased , resulting in a significant increased bioavailability as reflected by the bioavailability as reflected by the increase in the area under plasma increase in the area under plasma concentration time curve , it can be concentration time curve , it can be predicted that the required predicted that the required minimum effective concentration minimum effective concentration could be achieved in humans in could be achieved in humans in spite of the greater barrier spite of the greater barrier properties of human skin compared properties of human skin compared to rabbit skin.to rabbit skin.

7-An approximation of the 7-An approximation of the usefulness of the use of usefulness of the use of transdermal administration of transdermal administration of felodipine in humans can be felodipine in humans can be determined by estimating the determined by estimating the application area of the drug application area of the drug delivery system or the patch delivery system or the patch used to deliver the drug.used to deliver the drug.

MicroemulsioMicroemulsionn

SystemSystem

Amount of felodipine permeated(mg)Amount of felodipine permeated(mg)

after the following periods of time(min)after the following periods of time(min)

151530306060120120180180240240360360480480360360

II0.030.030.040.040.080.080.120.120.160.160.190.190.250.250.330.330.450.45

IIII0.010.010.010.010.030.030.050.050.080.080.100.100.150.150.200.200.250.25

IIIIII0.030.030.060.060.110.110.220.220.380.380.520.520.790.790.970.971.241.24

IVIV0.350.350.430.430.580.580.840.841.161.161.421.422.142.142.692.693.353.35

Fig(1):Permeation of Felodipine from its Alcoholic Solution in 0.1%SLS

0

1

2

3

4

0 200 400 600 800

Time(min)

Am

ou

nt

of

Felo

dip

ine

Perm

eate

d28%VA

19%VA

9%VA

Fig(1) : Calibration Curve of Felodipine in Rabbit Plasma.

y = 2,1526x

R2 = 0,9993

0102030405060708090

100

0 5 10 15 20 25 30 35 40 45

Concentration(nmol/L)

Pea

k A

rea

x10

000

Fig(2) : Mean Plasma Concentration Time Curve Following the Administration of Felodipine Oral Solution to Six Healthy Male Rabbits.

0

5

10

15

20

25

30

35

40

45

0 5 10 15 20 25 30

Time(hr)

Pla

sm

a C

on

ce

ntr

ati

on

(nm

ol/

L)

Rabbit 1

Rabbit 2

Rabbit 3

Rabbit 4

Rabbit 5

Rabbit 6

Fig(3) : Mean Plasma Concentration Time Curve of Felodipine Following the Administration of its Transdermal Patch to Six Male Rabbits.

0

1

2

3

4

5

6

7

8

9

0 20 40 60 80 100 120 140

Time(hr)

Pla

sm

a C

on

cen

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on

(n

mo

l/L

)

Rabbit 1

Rabbit 2

Rabbit 3

Rabbit4

Rabbit 5

Rabbit 6