Percutaneous delivery of thalidomide and its N-alkyl analogs.
OBJECTIVE
The purpose of this study was to determine the permeation parameters of thalidomide and three of its N-alkyl analogs and to establish a correlation between the physicochemical properties of these compounds and their percutaneous rates of absorption.


METHODS
In vitro permeation studies were performed from buffer, n-alkanols and various mixed components using vertical Franz diffusion cells fitted with human epidermal membranes.


RESULTS
Measured steady-state fluxes indicate that N-methyl thalidomide is a far better penetrant of human skin than the "parent molecule". However, fluxes through skin drop off markedly from that of the methylated compound when the chain length is extended to propyl and pentyl. However, they remain well above the flux of thalidomide, which is less than 0.025 microg/cm2/h.


CONCLUSIONS
The best skin permeant of this series was the N-methyl analog, which also exhibited the highest water (buffer) solubility compared to thalidomide, and the N-propyl and N-pentyl analogs. The N-propyl and N-pentyl analogs were more lipid soluble and exhibited higher partition coefficient values than the N-methyl analog. From all the permeability data using buffer, a series of n-alkanols and various combinations of solvents and enhancers as vehicles, the more water-soluble compound and not the more lipid soluble one was the best skin permeant.
Goosen
Colleen
C
Department of Pharmaceutics, School of Pharmacy, Potchefstroom University for Christian Higher Education, Republic of South Africa. fmscg@puknet.puk.ac.za
Laing
Timothy J
TJ
du Plessis
Jeanetta
J
Goosen
Theunis C
TC
Lu
Guang-Wei
GW
Flynn
Gordon L
GL
D000279:Administration, Cutaneous; D002626:Chemistry, Pharmaceutical; D015194:Diffusion Chambers, Culture / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D013792:Thalidomide / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D013792:Thalidomide