Daily oral cyclobenzaprine hydrochloride (HCl) has provided transient benefits in fibromyalgia, a chronic pain condition. To improve this effect, we evaluated sublingual formulations designed to drive transmucosal absorption. Two open-label studies evaluated the pharmacokinetics (PK), tolerability, and relative bioavailability of sublingual cyclobenzaprine HCl in healthy adults. In Study 1 (n = 24), three 2.8 mg sublingual formulations of cyclobenzaprine HCl containing potassium phosphate dibasic (A), sodium phosphate dibasic (B), or trisodium citrate (C) were compared to immediate release (IR) cyclobenzaprine HCl 5 mg. All sublingual formulations showed increased bioavailability (154% A, 126% B, and 125% C) and rapid absorption. Formulation A demonstrated the most favorable PK, with a ∼3 min absorption lag versus ∼37 min for oral IR, and a 783% higher dose-normalized AUC0-1. Formulation A was designated TNX-102 SL for further development. In Study 2 (n = 16), TNX-102 SL 2.8 and 5.6 mg exhibited dose proportionality and no food effect. Furthermore, this is the first report describing the active metabolite norcyclobenzaprine in clinical studies, showing an elimination half-life of ∼60 h. Oral hypoesthesia and abnormal taste were the most common adverse events. These findings support TNX-102 SL as a rapidly absorbed and efficient sublingual tablet formulation of cyclobenzaprine HCl, providing effective transmucosal delivery.
Daugherty et al. (Sun,) studied this question.