periodontal disease-associated peptidase activity was reduced over control values at
13 weeks (Hirasawa et al. 2000 ). These designs should permit the attainment of
higher local drug concentrations than is possible from systemic delivery. Although
further development of systems to improve gum contact time in small animals
would be useful (reviewed in Cleland 2001 ), difficulties of administration for own-
ers has the consequence that such products will be mostly limited to use by
veterinarians following dental scaling and tooth extraction procedures. In a note
of caution, a meta-analysis of human trials has concluded that there is rather weak
evidence to date to establish that these types of local delivery systems produce
significant additional clinical benefit when used as an adjunct to scaling and root
canal work (Hanes and Purvis 2003 ).
3.7 Sustained-Release Parenteral Veterinary Drug Delivery
SR parenteral formulations for livestock and companion animals are an important
sector of the pharmaceutical market in veterinary medicine, estimated at 40% of
the total veterinary CR market, which inturn is approximately 15% of the total
veterinary drug market (Medlicott et al. 2004 ). Some of the physiological differ-
ences in different species impacting on non-injected routes of delivery can be
overcome by s.c. or intramuscular (i.m.) injection and a strong case can be made
that long-acting injections of suspensions, solutions and implants are more
convenient than oral administration. Parenterally-administered SR formulations
usually yield higher bioavailability than oral ones and are the only routes
currently available for peptide and protein delivery (Matschke et al. 2002 ).
Negative aspects, however, include possible injection site irritation and inflam-
mation, unpredictable absorption rates, lack of in vitro–in vivo release correla-
tions, complex sterile formulation manufacturing requirements, and possible poor
“syringeability”. In addition, in food-producing animals, controlling the release
profile must balance the need to achieve therapeutic efficacy against prolonged
residual concentrations in edible tissues, so as not to lead to unduly prolonged
meat withholding times. Erratic, non-linear and therefore poorly predictable
depletion rates from IM injection sitesof CR formulated drugs in food producing
species, notably in cattle and pigs, have created major difficulties in setting meat
withholding times (see chapter, “Drug Residues”). This has led to the s.c. route
being favoured over i.m. injections in cattle and also to investigations into the
alternative of ear injections, as this isone part of the carcass that is not used for
human consumption. Specifically, extensive regulations cover the testing of SR
parenteral products in animals destined for the food chain in respect of establish-
ing reproducible, safe and effective drug release rates (Martinez et al.2008b).
A comprehensive review on the pros and cons of SR parenteral products is pro-
vided by Medlicott et al. ( 2004 ). These products range from oil- and liquid-based
injections, suspensions, microparticles, and in situ forming gels to implants and
they encompass selected therapeutic agents: notably antiparasiticides, antibacterials
Drug Delivery Systems in Domestic Animal Species 95