Effect of iontophoresis on in vitro skin permeation of an analogue of growth hormone releasing factor in the hairless guinea pig model.
The shortened analogue of growth hormone releasing factor (GRF) Ro 23-7861 (1) has a molecular weight of 3929 daltons [equivalent to GRF (1-29)] and is more potent than the endogenous GRF (1-44). The in vitro hairless guinea pig model and vertical and horizontal diffusion cell assemblies were used to study the effect of iontophoresis on the permeability to skin of 1. The transport of 1 across the skin was studied by monitoring the rate of its appearance in the receiver compartment with a radioimmunoassay. No permeability of 1 was observed without iontophoresis, whereas with iontophoresis, the permeability of 1 was significant. For example, at a current density of 0.23 mA/cm2 and buffer concentration of 0.05 M, the flux of 1 was 56.8 +/- 8.21 ng/cm2.h. The flux of 1 was independent of the design of the permeation apparatus, the electrodes, the donor and receiver volumes, the type of current (constant or pulsed), and the frequency of the pulsed current. The flux of 1 increased curvilinearly with the increase in salt concentration of the buffer and linearly with the increase in current.
Kumar
S
S
Pharmaceutical Research and Development, Hoffmann-La Roche, Inc., Nutley, NJ 07110.
Char
H
H
Patel
S
S
Piemontese
D
D
Iqbal
K
K
Malick
A W
AW
Neugroschel
E
E
Behl
C R
CR
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007478:Iontophoresis; D008969:Molecular Sequence Data; D012869:Skin Absorption / Q000502:physiology*
C077201:Ro 23-7861; D013007:Growth Hormone-Releasing Hormone