TITLE:
Transdermal Formulation Development and Topical Administration of Atenolol to Cats
AUTHORS:
Sumeia M. Mohamed, John Mark Christensen, Nicole LeBlanc
KEYWORDS:
Atenolol, Transdermal Delivery, Formulation, Cats
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.11 No.3,
March
31,
2020
ABSTRACT: Atenolol diffusion through synthetic membrane, cloned human epidermis,
and cat ear skin was performed utilizing a Franz diffusion cell. Transdermal drug diffusion
enhancers’ ethanol, glycerol, propylene glycol, polysorbate 80 and Dimethyl
isosorbide (DMI) were added to the topical formulations and tested for their
ability to enhance drug permeation through the test membranes. Topical
formulation with penetration enhancers showed a rapid burst of atenolol
diffusion for the first two hours (35.5 to 40 μg/ml)
followed by a zero-order sustained diffusion of 2.7 μg/cm2/h of atenolol for up to twenty-four hours after application to test
membranes. Increased atenolol flux through different test membranes was
greatest for synthetic membrane. The topical application of the optimized
atenolol formulation to cat skin containing permeation enhancers aided
transdermal atenolol drug delivery to treat cats with hypertrophic obstructive
cardiomyopathy. The optimum topical formulation demonstrated two fluxes through
cat skin, the burst flux (15.7 μg/cm2/h) and a sustained flux (2.7 μg/cm2/h). Measured atenolol concentrations in cats at 3, 6 and 12 hours after
transdermal atenolol application were 432.7 ng/ml ± 323.3, 262.4 ng/ml ± 150.1,
and 253.3 ng/ml ± 133.6 respectively. Six of 7 cats achieved therapeutic serum
atenolol levels (200 ng/ml) for at least one time point. Five of 7 cats had
therapeutic serum atenolol concentrations 3
hours post-atenolol. At the 6 hours post-atenolol time point, Four had a
therapeutic serum atenolol concentration while at 12 hours post-atenolol
dosing, 4 of 7 cats had therapeutic serum atenolol concentrations. Transdermal
atenolol administered at 25 mg q12h resulted in clinically therapeutic serum
atenolol concentrations in the majority of healthy cats. The optimum
transdermal formulation enabled good drug delivery feasible for transdermal
application in a clinical trial in cats.