# Single‐Dose Pharmacokinetic Assessment of TNX‐102 SL (Cyclobenzaprine HCl Sublingual Tablets): Results From Randomized, Open‐Label Studies in Healthy Volunteers

## TL;DR

This study evaluates a sublingual tablet of cyclobenzaprine HCl, showing faster absorption and higher effectiveness compared to traditional oral forms for fibromyalgia treatment.

## Contribution

The study introduces TNX-102 SL, a sublingual formulation of cyclobenzaprine HCl with improved pharmacokinetics and bioavailability.

## Key findings

- Sublingual formulations showed increased bioavailability compared to immediate release oral forms.
- Formulation A (TNX-102 SL) demonstrated rapid absorption with a 783% higher AUC0-1 compared to oral IR.
- TNX-102 SL showed dose proportionality and no food effect, with norcyclobenzaprine having an elimination half-life of ~60 hours.

## Abstract

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.