Results and Discussion Continued

1. Results and Discussion Continued By: Kristin Ackermann Amanda Rohs Blanca Skelding

2. Determining Intrinsic Permeation Rate • Saturated drug solution, Cs, in donor compartment • Monitor permeation of drug through membrane by sampling receptor compartment • Permeation rate is a function of: • Partition coefficient of drug toward membrane • Thickness of diffusion boundary layer (on both sides of membrane)

3. Schematic of Drug Conc. Profile

4. (Eq. 9) Permeation Rate Per Unit Area • In Equation (9) above: • D = diffusivity of drug through membrane • K = partition coefficient • l = membrane thickness • km = mass transfer coef. • C1 = conc. of drug in donor phase boundary • C2 = conc. of drug in receptor phase boundary • C = conc. Of drug in bulk soln. • Q = cumulative amount of drug permeated

5. Term 1 Term 2 Term 3 (Eq. 9) Explanation of Terms • Term 1: Solute diffusion in receptor solution mass balance • Term 2: Diffusivity through membrane • Term 3: Solute diffusion in donor solution mass balance

6. More Explanation • Rearranging Eqn (9) results in Eqn (10): • If the mixing is so vigorous that diffusion boundary layer can be eliminated, Eqn (10) is simplified to: (Eq. 10) (Eq. 11)

7. Effect of Diffusion Boundary Layer • The effect of diffusion boundary layer on rate of drug permeation can be represented in Eqn (12a). Where • γ represents the permeation rate per area when boundary layer is present divided by the permeation rate when the boundary layer is negligible • Sh->∞ represents the mass transfer coef. approaching infinity, which would cause the boundary layer effects to be negligible. (Eq. 12a)

8. Effect of D.B.L. (continued) • Substituting Eqns (10) and (11) into Eqn (12a), Eqn (12c) results: Where Shl is the Sherwood number in terms of membrane thickness • Since Sh = Shl(D/Df)(d/l), Eqn (12c) becomes Eqn (13): (Eq. 12c) (Eq. 13)

9. Effect of D.B.L. (continued) • From Eqn (13), the effect of the diffusion boundary layer on the rate of drug permeation can be evaluated • It can be observed that large partition coefficient and a small Sh will cause significant effect on intrinsic permeation rate

10. Example • When water is used as elution media and a polymeric membrane, 2 drugs of similar molecular weight have the following parameters: Drug I D = 4.5 X 10-7 cm2/s Df = 7 X 10-6 cm2/s K = 50.2 L = 0.05 cm D = 0.9 cm Drug II D = 4.5 X 10-7 cm2/s Df = 7 X 10-6 cm2/s K = 0.05 L = 0.05 cm D = 0.9 cm

11. Example • For both drugs, Sh = 229 • For Drug I, g = 0.063 • For Drug I, g = 0.995 • Experimental permeation rate = 1.0 mg/(cm2h) • Intrinsic permeation rate is: • Drug I = 1.5mg/(cm2h) • Drug I = 1.0mg/(cm2h)

12. Example (continued) • Experimental permeation rate for drugs I and II is approx. 33% and 0% less than intrinsic rate • Examples illustrate importance of partition coefficient in determination of permeation rate

13. Conclusion • Mass transfer characteristics of benzoic acid from a disk surface were investigated to calibrate in vitro membrane permeation cell • Solution solubility and dissolution rate of benzoic acid were measured in aqueous PEG 400 • Correlating equation for mass transfer coefficients was established using Sh-Re-Sc equation • Effect of diffusion boundary layer on rate of controlled drug release can now be evaluated accurately using correlation obtained in study

14. Questions??