Assessment of clotrimazole gels for in vitro stability and in vivo retention in the frontal sinus of dogs.
OBJECTIVE
To evaluate the stability and retention of viscous formulations of the antifungal drug clotrimazole in vitro and to evaluate retention times, absorption, and histologic response to these compounds when placed in the frontal sinus of dogs.


METHODS
6 male Beagles.


METHODS
1% clotrimazole gels were formulated with hydroxypropyl cellulose, poloxamer, and carboxymethylcellulose sodium bases. Commercially available 1% clotrimazole creams were also evaluated. Each compound was incubated at 37 degrees C in a funnel. Volume retained and clotrimazole stability were evaluated for 4 weeks. Six compounds were then chosen for in vivo evaluation. The frontal sinuses of 6 dogs were filled with 1 of the 6 compounds. Computed tomographic evaluation was performed weekly for up to 4 weeks to evaluate gel retention. Blood samples were collected to evaluate clotrimazole absorption. Following euthanasia, sinuses were examined histologically.


RESULTS
Commercially available clotrimazole creams were not retained in funnels in vitro. In vivo, hydroxypropyl cellulose- and carboxymethylcellulose-based gels resulted in the most severe inflammatory response and were retained the longest. Poloxamer-based gels had a shorter retention time and were associated with less inflammation. Clotrimazole was minimally absorbed. Despite a marked inflammatory response to several of the clotrimazole-containing gels, no notable adverse clinical responses were observed.


CONCLUSIONS
Poloxamer gels had the most promise for improving drug contact within the frontal sinus of dogs, while limiting the inflammatory response. Poloxamer gels have the additional benefit of improved handling as a result of reverse gelation (ie, they gel when warmed to 37 degrees C).
Mathews
Kyle G
KG
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Linder
Keith E
KE
Davidson
Gigi S
GS
Goldman
Rebecca B
RB
Papich
Mark G
MG
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D003022:Clotrimazole / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D004285:Dogs / Q000378:metabolism*; D004355:Drug Stability; D005626:Frontal Sinus / Q000000981:diagnostic imaging / Q000378:metabolism*; D005782:Gels / Q000737:chemistry / Q000378:metabolism; D008297:Male; D020442:Poloxamer / Q000737:chemistry / Q000378:metabolism; D014057:Tomography, X-Ray Computed / Q000662:veterinary
D000935:Antifungal Agents; D005782:Gels; D020442:Poloxamer; D003022:Clotrimazole