Acyclovir is an antiviral drug used in the treatment and prevention of herpes simplex and
varicella-zoster viral infections. The major problem in the transdermal delivery of
acyclovir is the permeation in sufficient amounts to deeper layers of the skin and into the
systemic circulation. Acyclovir is a hydrophilic substance with a low partition coefficient,
resulting in poor penetration through the excellent barrier of the skin, the stratum
corneum.
In an attempt to enhance the transdermal permeability of acyclovir, the aim of this study
was to employ terpenes as possible penetration enhancers. Terpenes are constituents
of natural essential oils, with widespread medicinal use including in aromatherapy. The
terpenes used in this study were 1,8-cineole, limonene, menthol, menthone, and 13-
myrcene.
Terpenes are not only used as penetration enhancers, but are even more often present
in drugs and cosmetics. Limited studies have been done concerning the penetration of
terpenes through the skin. Thus, not only the effect of the terpenes on the penetration of
acyclovir, but also the penetration of the terpenes themselves were studied. The
influence of acyclovir on the penetration of the terpenes was also determined.
In vitro permeation experiments were performed on human skin using Franz diffusion
cells. The skin was pretreated with a 5 % solution of the terpene in ethanol and left for
30 minutes to enable ethanol evaporation and terpene incorporation into the skin.
Saturated aqueous solutions of acyclovir (pH 7.4) were added in the donor compartment
before and after skin pre-treatment. The acyclovir concentration retrieved from the
receptor compartment of the Franz cells was analyzed by HPLC. The amount of terpene
that penetrated were semi-quantitatively determined by GC.
Penetration of acyclovir was significantly enhanced by two terpenes, viz. 1,8-cineole and
menthol. The extent of enhancement was, however, not large enough to be of clinical
use. The enhancement in acyclovir penetration observed upon ethanol pre-treatment
alone, or in the presence of limonene, menthone or ~-myrcene, was not significant.
Penetration enhancement of acyclovir by the terpenes was in accordance with previous
studies, which postulated better enhancement of hydrophilic drugs by hydrophilic
terpenes.
Large percentages of the terpenes with log P values within the optimum log P range (1 -
3) penetrated, as was found with menthone and menthol. Penetration decreased
accordingly as the log P, and thus lipophilicity, increased. Stratum corneum retention is
regarded as the most plausible explanation for this phenomenon. In the case of 1,8-
cineole, enhancer pooling in the stratum corneum could be a possible reason for its poor
penetration. Acyclovir significantly influenced the penetration profiles of some of the
terpenes, but no clear explanation could be given. / Thesis (M.Sc. (Pharm.))--North-West University, Potchefstroom Campus, 2004.
| Identifer | oai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/301 |
| Date | January 2003 |
| Creators | Myburgh, Mariaan |
| Publisher | North-West University |
| Source Sets | North-West University |
| Detected Language | English |
| Type | Thesis |
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