3.3 Topical Formulations and Transdermal Patches
Topical formulations including dusting powders, creams, ointments, pastes, pour-
ons, drenches and spot-ons are generally designed to either kill internal parasites
following absorption across thestratum corneum, or to kill parasites on the skin as a
result of spreading out from a skin depot. In the case of topical application of anti-
parasitic drugs in oily bases, such as fipronil and imidacloprid, the drug redistri-
butes back to skin appendages, primarily pilo-sebaceous units, which in turn act as a
30–60 day reservoir for further CR in cutaneous oils onto the skin (Fig. 2 ) (Dryden
et al. 2000 ). Topically-applied selamectin, formulated with isopropyl alcohol, to
dogs produces 5% bioavailability (Sarasola et al. 2002 ). While this level of bio-
availability is probably too low to cause systemic side-effects associated with the
avermectin class in certain dog breeds, selamectin’s mechanism of action in killing
heartworm relies on reaching the circulation, as distinct from the poorly-absorbed
oil-based spot-on formulations, which are designed to kill fleas on the skin. Sela-
mectin’s high potency results in acceptable efficacy despite its relatively low
bioavailability. Studies following spot-on administration of radiolabelled fipronil
proved that the label was concentrated in the keratinocyte layer and that it was
detectable at skin sites distant from initial application, thus confirming low bio-
availability and indicating spread from the initial site of application (Cochet et al.
1997 ). In contrast to patches, where drug release from the device is the rate-limiting
step for absorption, diffusion through thestratum corneumis the key determinant of
efficacy for topically-applied drugs (Riviere and Papich 2001 ). Factors influencing
dermal penetration of porcine skin have been reviewed recently by Riviere and
Brooks ( 2009 ). Considerable PK data are available for ivermectin pour-on products
in cattle and the convenience of this route, lower cost and lack of requirement for
skilled labour, is favoured by farmers over oral bolus devices. Recently, Laffont
et al. ( 2003 ) demonstrated that most of the absorbed ivermectin from pour-ons
resulted from skin-licking and subsequent oral absorption amongst herds. This
discovery led to concerns over variable ivermectin dosing from pour-ons, unin-
tended dosing of animals and the potential for residues in edible tissues exceeding
the maximum residue limit set by the EMEA.
Table 3Selected nasal vaccine delivery systems in veterinary species
Species Antigen Delivery system/adjuvant Reference
Feline FIV p24Gag E. coliLT(R192G) Leavell et al. ( 2005 )
Sheep T. gondiitachyzoites PLG microspheres Stanley et al. ( 2004 )
Bovine porcine serum albumin Alginate microparticles Rebelatto et al. ( 2001 )
Porcine (OmlA) fromActinobacillus
pleuropneumoniae
CpG ODNs in biphasic lipids Alcon et al. ( 2005 )Canine Live-attenuated
B. bronchiseptica
None required Davis et al. ( 2007 )FIVFeline Immunodeficiency Virus;LTHeat labile enterotoxin;PLGPoly(lactide)co-glycolide;
OmlAOuter membrane lipoprotein A;ODNoligodeoxynucleotides
88 D.J. Brayden et al.