Transmucosal administration of drug compositions for treating and preventing disorders in animals

#In one embodiment, the present invention relates to the transmucosal administration of pharmaceutical compositions to an animal for use in treating or preventing disorders. In particular, embodiments of the invention encompass compositions comprising and methods of using various active agents for combating various diseases or conditions in an animal, preferably a domestic animal, by transmucosally administering a prophylactically or therapeutically effective amount of one or more active agents to an animal in need thereof. Preferred administering means include, but are not limited to, sprays or mists of the one or more active agents into the oral cavity of the animal.

#Pharmaceutical compounds originally developed for human use have also been used in veterinary medicine. However, the effectiveness of human drugs in non-human animals is unpredictable because of metabolic differences between humans and the various non-human animal species. Even for individuals within a species, the effectiveness of a particular drug can be highly variable. For example, H1-receptor antagonists such as clemastine have been used as antihistamines for both humans and animals. However, doses which are effective in humans have been found to be ineffective in canine and equine subjects because of poor oral bioavailability and rapid elimination of the clemastine (see Hansson et al., Veterinary Dermatology 2004, 15, pages 152-158; and Törneke et al., J. Vet. Pharmacol. Therap. 26, pages 151-157, 2003). Therapeutic plasma levels of clemastine in canine and equine subjects were only obtained by intravenous administration using relatively high (compared to human) doses, which severely limit the utility of clemastine for veterinary applications.

#It is known that certain biologically active compounds are better absorbed through the oral mucosa than through other routes of administration, such as through the stomach or intestine. However, formulations suitable for such administration through the oral mucosa present their own problems. For example, the biologically active compound must be compatible with the other components of the composition such as propellants, solvents, etc. Many such formulations have been proposed. For example, U.S. Pat. No. 4,689,233 to Dvorsky et al., describes a soft gelatin capsule for the administration of the anti-coronary drug nifedipine dissolved in a mixture of polyether alcohols. U.S. Pat. No. 4,755,389 to Jones et al., describes a hard gelatin chewable capsule containing nifedipine. A chewable gelatin capsule containing a solution or dispersion of a drug is described in U.S. Pat. No. 4,935,243 to Borkan et al. U.S. Pat. No. 4,919,919 to Aouda et al., and U.S. Pat. No. 5,370,862 to Klokkers-Bethke, describe a nitroglycerin spray for administration to the oral mucosa comprising nitroglycerin, ethanol, and other components. An orally administered pump spray is described by Cholcha in U.S. Pat. No. 5,186,925. Aerosol compositions containing a hydrocarbon propellant and a drug for administration to a mucosal surface are described in U.K. 2,082,457 to Su, U.S. Pat. No. 3,155,574 to Silson et al., U.S. Pat. No. 5,011,678 to Wang et al., and by Parnell in U.S. Pat. No. 5,128,132. It should be noted that these references discuss bioavailability of solutions by inhalation rather than through the membranes to which they are administered. Each of the above-identified references is incorporated herein by reference in its entirety.

#FIG. 1 shows the mean plasma concentrations of meloxicam when administered using two different dosage forms (oral suspension and transmucosal oral mist (hereinafter, “TMOM™”)) at the same dosage (˜0.2 mg/kg). The oral suspension was administered to the dog orally and was swallowed. The mist was sprayed into the oral cavity of the dogs.

#FIG. 2 shows a comparison of the pharmacokinetic parameters for administration of meloxicam by oral suspension and administration using TMOM™ to dogs at a dosage of about 0.2 mg/kg. The AUC represents the area under the curve or the total amount of drug exposure to the animal following administration by the two different dosage forms. The Cmax represents the maximum plasma concentration of meloxicam measured in ng/ml when administered by the dosage forms. The Tmax denotes the time it takes to reach maximum plasma concentration of meloxicam achieved following administration of both dosage forms. The t1/2 is the calculated rate of distribution or elimination of the meloxicam when administered by both dosage forms.

#FIG. 3 shows the results of bioequivalence testing in dogs between meloxicam administered via TMOM™ and administration of an oral suspension (˜0.2 mg/kg).

#In one embodiment, the present invention is directed to compositions for transmucosal administration to animals comprising at least one active agent and a pharmaceutically acceptable carrier.

#In another embodiment, the present invention encompasses novel methods of transmucosally administering compositions comprising a therapeutically or prophylactically effective amount of at least one active agent to an animal in need thereof.

#In one embodiment, the compositions of the present invention may be administered to any mucosal surface of the animal, preferably a membrane of the oral mucosa, including lingual surfaces, sublingual surfaces, buccal surfaces, palatal surfaces, and pharyngeal surfaces, preferably buccal or gingival surfaces. In other embodiments, the compositions of the present invention may also be administered to more than one membrane of the oral mucosa, for example the lingual and sublingual surfaces or the lingual, sublingual and buccal surfaces, etc. In yet other embodiments, the compositions of the present invention can be administered to the area of the oral cavity of an animal between the teeth and cheek, thereby allowing the compositions of the present invention to contact at least the buccal and gingival mucosa.