1. SIDE BY SIDE CELL pump spectrophotometer computer Magnetic engine
surge chamber
spectrophotometer
computer
Magnetic engine
Donor
Receiver
Teflon adapter
solid drug
membrane
stirrer
Thermostatic unit
jacket

2. 2 - DRUG DIFFUSION MEASUREMENT
TEFLON ADAPTER
DONOR CHAMBER
RECEIVER
CHAMBER
THERMOSTATIC
JACKET
MAGNETIC STIRRERS

3. DRUG CONCENTRATION INCREASE
2 - MODELING
DONOR
RECEIVER
POWDER DISSOLUTION
DRUG PERMEATION
jacket
jacket
DRUG CONCENTRATION INCREASE
STIRRER

4. MATHEMATICALL MODELING

5. SOLID SURFACE VARIATION: MONODISPERSED PARTICLES SYSTEM
SOLID DRUG
Particles initial surface area

6. FICK LAW
1st stagnant layer
membrane
2nd stagnant layer

7. BOUNDARY CONDITIONS

8. BOUNDARY CONDITIONS

9. BOUNDARY CONDITIONS

10. SIMULATION: NO DISSOLUTION
Vr = Vd
H = Stagnant layer thickness
*hm
Dm = 5.3*10-6 cm2/s
*hm
*hm
D1 = 8.8*10-6 cm2/s
*hm
D1 = D2
Kp = 0.8
hm = 100 mm
S = 10 cm2

11. SIMULATION: PROFILE CONCENTRATION
S = 10 cm2
Vr = Vd
Dm = 5.3*10-6 cm2/s
D1 = 8.8*10-6 cm2/s
D1 = D2
Kp = 0.8
hm = 100 mm
h1 = h2 = 0.5*hm

12. SIMULATION: DISSOLUTION
Vd = 100 cm3
Vr = 800 cm3
h1 = h2 = hm=100mm
Kp = 0.8
Dm = 5.3*10-6 cm2/s
D1 = 8.8*10-6 cm2/s
D1 = D2
Kd = 10-6cm/s
A = 5000 g/cm2
Cs = mg/cm3
S = 10 cm2

13. SIMULATION: STEADY STATE APPROXIMATION
Cd = Cd0 (constant drug concentration in the donor)
Cr = 0 (sink conditions in the receiver)
FICK eq. solution (only membrane) is:
For t ∞
Membrane Permeability

14. For a trilaminate system the solution is:
For t ∞
For a trilaminate system the solution is:

15. SIMULATION: LINEAR PROFILES (THIN MEMBRANES)

16. SIMULATION: LINEAR PROFILES (THIN MEMBRANES)
EMPIRICAL APPROACH

17. 3 - DRUG DIFFUSION COEFFICIENT MEASUREMENT REQUIRES THE DETERMINATION OF:1
DRUG SOLUBILITY CS IN THE RELEASE ENVIRONMEMT 2
DRUG DIFFUSION COEFFICIENT DW IN THE RELEASE ENVIRONMEMT 3
DRUG POWDER DISSOLUTION CONSTANT KDP 4
DRUG PARTITION COEFFICIENT Kp (MEMBRANE/RELEASE ENVIRONMENT) 5
THICKNESS OF STAGNANT LAYERS SANDWICHING THE MEMBRANE

18. CASE STUDY: THEOPHYLLINE AND ALGINATES
THEOPHYLLINE MONOHYDRATED
- Carlo Erba , Milano
- (C7H8N4O2*H2O); MW 198, WHITE CRYSTALLINE POWDER
- DENSITY 1.49 ± 01 g/ cm3 (Helium picnometer)
- SURFACE AREA = 2941 cm2/g (mercury porosimeter)
- U.V. PEAK ABSORBANCE 271 nm
ALGINATE:
- Protanal LF 20/ 60, Pronova Biopolymer, Drammen, Norway
- THEY ARE EXTRACTED FROM BROWN SEAWEED
- SEQUENCE OF GULURONATE AND MANNURONATE (LF 20/60: 70% GULURONATE)
- THEY FORM STRONG PHYSICAL GELS IN PRESENCE OF DIVALENT IONS (TYPICALLY Ca++)

19. Ca++
EGG BOX CONFIGURATION
Ca++

20. DW = (8.2 ± 0.6)*10-6 cm2/s (DISTILLED WATER 37°C)
DRUG SOLUBILITY CS IN THE RELEASE ENVIRONMEMT
Cs = ± 104 mg/cm3 (DISTILLED WATER 37°C) 2
DRUG DIFFUSION COEFFICIENT DW IN THE RELEASE ENVIRONMEMT
Kd = 0.62*DW2/3 w1/2 *n-1/6
DW = (8.2 ± 0.6)*10-6 cm2/s (DISTILLED WATER 37°C)
IDR

21. 3 DRUG POWDER DISSOLUTION CONSTANT KDP SEALING TAPE Donor jacket
Magnetic engine
Donor
solid drug
jacket
SEALING TAPE

22. t = 0 t > 0 DISSOLUTION Rp Rp0 - SINK CONDITIONS
- Np MONOSIZED SPHERICAL PARTICLES (Rp0 INITIAL RADIUS)
t = 0
Rp0
t > 0 Rp
DISSOLUTION
PARTICLES SURFACE
Md =
drug amount in the donor (soluble)
Mp =
solid particle mass

23. A = Particles initial surface area
Mp0 = initial particles mass

24. KDP = 1.2*10-3 cm/s

25. 4 24 h C∞ M0 = V*C∞+Vg* Cg∞ Kp = Cg∞ /C∞
DRUG PARTITION COEFFICIENT Kp (MEMBRANE/RELEASE ENVIRONMENT)
Cylindrical gel V
IDR Vg
(DISTILLED WATER 37°C)
C0 = 20 mg/cm3
24 h C∞
M0 = V*C∞+Vg* Cg∞
Kp = Cg∞ /C∞

26. MEMBRANE STAGNANT LAYER STAGNANT LAYER5
THICKNESS OF STAGNANT LAYERS SANDWICHING THE MEMBRANE
MEMBRANE
Donor
Receiver
STAGNANT LAYER
STAGNANT LAYER
jacket
jacket
stirrer
stirrer

27. Donor
DRUG
jacket
stirrer
hss = 60.7 mm
STAGNANT LAYER

28. 4 - RESULTS Vd = 100 cm3 Dm = (5.1± 0.64)*10-6 cm2/s Vr = 100 cm3
S = 10 cm2
%P = 4
- Model
- Linear approximation
Experimental data

29. T = 25°C 2% 4% 1%

30. T = 37°C 2% 4% 1%

31. MEMBRANES CHARACTERISTICS

32. DIFFUSION COEFFICIENTS