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

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)

Schematic of Drug Conc. Profile

Permeation Rate Per Unit Area  In Equation (9) above: D = diffusivity of drug through membrane K = partition coefficient l = membrane thickness k m = mass transfer coef. C 1 = conc. of drug in donor phase boundary C 2 = conc. of drug in receptor phase boundary C = conc. Of drug in bulk soln. Q = cumulative amount of drug permeated (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 (Eq. 9) Term 1Term 2Term 3

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)

 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. Effect of Diffusion Boundary Layer (Eq. 12a)

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

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

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 cm 2 /s D f = 7 X cm 2 /s K = 50.2 L = 0.05 cm D = 0.9 cm Drug II D = 4.5 X cm 2 /s D f = 7 X cm 2 /s K = 0.05 L = 0.05 cm D = 0.9 cm

Example  For both drugs, Sh = 229  For Drug I, g =  For Drug I, g =  Experimental permeation rate = 1.0 g/(cm 2 h)  Intrinsic permeation rate is: Drug I = 1.5g/(cm 2 h) Drug I = 1.0g/(cm 2 h)

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

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

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