Comparative and Veterinary Pharmacology

administration is during the dry period, when it is easier to maintain high concen-
trations in the teat and gland over several weeks. The goals of dry cow therapy
include elimination of persistent low grade infections and prevention of colonisa-
tion in an immunologically-vulnerable period. For economic reasons, based on
regulatory requirements to calculate safe withdrawal times for residues in milk,
antibiotic therapy for clinical mastitis in the lactating cow requires rapid drug
effects with short half-lives and the physico-chemical properties of the formulation
are designed so that high concentrations are maintained in milk but for relatively
short periods (Gruet et al. 2001 ).Lactatingcow intramammary antibiotic aqueous-
based products are formulated to achieve immediate onset of action with treatment
starting for a maximum of 5–7 days. The aim is to achieve rapid elimination so as to
ensure short milk withdrawal times. Drug delivery technologies for thedrycow are
designed on the principle of inducing high local teat and tissue concentrations by
parenteral injection or more usually intramammary infusions or combinations
thereof. Most dry cow intramammary formulations of antibiotics rely on peanut
or mineral oil-based drug suspensions in the absence of wetting agents and indeed
they generally incorporate water repellant chemicals; these are more likely to
ensure binding to tissue proteins and secretions and have reduced systemic
bioavailability (Gruet et al. 2001 ). Mastitis may cause epithelial disruption and
this may aid drug penetration into deeper sections of the udder, although data to
confirm this remain scant (Gehring and Smith 2006 ). Novel intramammary delivery
technologies being researched are presented in Table 5. Many are based on antibi-
otic or antiseptic incorporation into a range of microparticles, nanoparticles, and
liposomes for uptake by phagocytes and subsequent release over several weeks.
Gruet et al. ( 2001 ) have advocated a prophylactic routine of teat antiseptic wash
together with local administration of SR antibiotics at the time of drying off, but
have also noted that no treatments seem particularly effective againstS. aureusand
that this remains a major challenge.

Table 5Controlled release formulations for treatment of mastitis or brucellosis*
Formulation Comment Reference
Alginate beads (dried gel-
based particles) containing
ampicillin

In vitro data on drug release Torre et al. ( 1998 )

Liposomes containing
streptomycin

Intramammary infusions give good

outcomes in combination with

oxytetracycline (i.m.)*

Nicoletti et al. ( 1989 )

PLG microspheres containing
Povidone–iodine

In vitro release for 28 days with an

initial 2-day burst release

Park and Han ( 2002 )

Aqueous solution or oily
suspension containing
micronised
benzylpenicillin

Perfused udders from lactating cows

in vitro

Ehinger and Kietzmann

( 2000 )

Polymeric microparticles of
ceftiofur

In vitro data; potential as dry cow

therapy

Bodmeier et al. ( 1997 )

Drug Delivery Systems in Domestic Animal Species 93