Effects of Intradermal Administration Volume Using a Hollow Microneedle on the Pharmacokinetics of Fluorescein Isothiocyanate Dextran (M.W. 4,000)

Abstract

Purpose: Hollow microneedles (hMNs) have been gaining attention as a tool to enable the intradermal (i.d.) administration of pharmaceutical products. However, few reports have examined the effect of administration volume on distribution in the skin and pharmacokinetics parameters after i.d. injection. In the present study, a model middle molecular weight compound, fluorescein isothiocyanate dextran (M.W. 4,000, FD-4), was selected, and blood concentration-time profiles after i.d. and subcutaneous (s.c.) injections with different administration volumes were compared.

Methods: FD-4 solution was injected i.d. using a hMN or injected s.c. with a 27 G needle. Pharmacokinetics and dermatokinetics of FD-4 were analyzed using a compartment model. The skin distribution of iodine, as an X ray tracer, was used to evaluate drug disposition.

Results: With the administered drug assumed to be absorbed from the broad injection site into blood vessels in the upper and lower dermis by rapid (k_rapid) and slow (k_slow) first-order absorption rate constants, respectively, better agreement of observed and theoretical values was obtained. Furthermore, the fraction, F, of the administered dose absorbed with k_rapid decreased with the increase in injection volume after i.d. injection, although the pharmacokinetics parameters were almost the same regardless of administration volume after s.c. injection.

Conclusion: The drug distribution in the skin may be related to the obtained pharmacokinetics parameters suggested that the number of needles in the MN system and the total administration volume should be considered in designing hMN systems. The present results provide useful information that may support effective drug delivery with hMNs.

Keywords: microneedle; middle-size biomolecules; pharmacokinetics; transdermal delivery.