Carprofen Permeation Test through Porcine Ex Vivo Mucous Membranes and Ophthalmic Tissues for Tolerability Assessments: Validation and Histological Study.

Carprofen (CP), a non-steroidal anti-inflammatory drug (NSAID), is profusely used in veterinary medicine for its analgesic and anti-inflammatory activity. Some undesirable effects are associated with its systemic administration. Alternative local routes are especially useful to facilitate its administration in animals. The main aim of this paper is to validate the suitability of ex vivo permeation experiments of CP with porcine mucous membranes (buccal, sublingual and vaginal) and ophthalmic tissues (cornea, sclera and conjunctiva) intended to be representative of naïve in vivo conditions. Chromatographic analysis of CP in membrane-permeated samples and drug-retained have been validated following standard bioanalytical guidelines. Then, recovery levels of drugs in tissue samples were assessed with aqueous phosphate buffered saline (PBS) buffer to preserve the histological integrity. Finally, as a proof of concept, a series of CP permeation tests in vertical Franz diffusion cells has been performed to evaluate permeation flux and permeability constants in all tissues, followed by a histological study for critical evaluation. Furthermore, synthetic tissue retention-like samples were prepared to verify the value of this experimental study. Results show linear relationships with good determination coefficient (R