Mucoadhesive Tacrolimus Formulations for Buccal Application: A Formulation and Drug Delivery Feasibility Study for...

Tacrolimus is a potent calcineurin inhibitor suitable for the local treatment of oral mucosal immune-mediated diseases; however, no buccal formulation is currently available. The main objective of this work was to develop a mucoadhesive, semi-solid formulation containing tacrolimus that has adequate mucoadhesion salivation, and effective mucosal penetration with low systemic availability. A series of tacrolimus containing semisolid formulations based on chitosan, carbomer and hypromellose (HPMC) as mucoadhesive polymers were developed. Their rheologic behavior, pH value, macroscopic and microscopic properties as well as mucoadhesion and mucosal penetration were investigated. Lactate buffer was successfully used to stabilize chitosan against hydrolysis. It was shown that diols of different chain length, like 1,2-propanediol 1,2-pentanediol and 1,2-hexanediol improved mucosal penetration but reduced mucoadhesion due to gel matrix weakening. After 60 min in the mucoadhesion cell, mucosal tacrolimus amounts versus salivary wash-off for the diols were 0.78 ± 0.09 µg/cm² versus 0.47 ± 0.20% for 20% 1,2-propanediol, 1.99 ± 0.23 µg/cm² versus 14.26 ± 3.01% for 40% 1,2-propanediol, 3.56 ± 0.29 µg/cm² versus 25.04 ± 1.68% for 20% 1,2-pentanediol, and 3.66 ± 0.25 µg/cm² versus 28.13 ± 4.00% for 20% 1,2-hexanediol. A series of tacrolimus formulations with different degrees of mucoadhesion, salivary retention and penetration characteristics was successfully developed.